AN EXAMlNAlïON OF THE EFFECTS OF PRENATAL ALCOHOL EXWSURE ON SCHOOL-AG€ CHILOREN IN A MANITOBA FlRST NATION

COMMUNITY.

A Study of Fetal Alcohol Synômm Prevalence and Dyamorphology.

A Thesis Submitted to the Faculty of Graduate Studies

in Partial FuiMment of the Requirements for the ûegm of

MASTER OF SCIENCE

Department of H u m Genetics University of Manitobr Winnipeg, Manitoba

@ Copyright by Wbm L. Kowlessar 1997.

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Abstract

A cross-sectional sunrey was conduded in one First Nation Comrnunity in

Manitoba to detemine the prevalenœ of Fetal Alcdrol Syndrome (FAS) among

school-aged children (ages 5 years ta 15 years). The study consisted of four

parts: a matemal interview, where mothen were questioned about family

dynamics. pregnancy and family histm-es, as well as alcohol use during

pregnancy using the TWEAK saeening questionnaire; review of the child's birth

records, to confinn alcohol exposures reporteci by the mother; Dysmorphology

assessment by a dinical geneticist; and psychducational testing by a trained

retired teacher. The geneticist and teacher w r e blind to the alcohol exposure

status of each child at the time of assessment-

Two hundred and seven consents were wllected by two local

coordinators, 178 of these were eligible for study (73% ascertainment rate).

Forty-six percent of the children studied had been exposed to alcohol in utero,

and 30% were exposeci to high levels of alcohol. Out of the 178 children

studied, 11 were identified as FAS. An additional 7 children were identified as

Partial FAS . Thus, in total 10% (1 811 78) of children had physical evidence of

being adversely affecteci by pmnatal alcohol exposure. Prevalence of FAS in

this community ranges from 31 to 62 per 1 0 children. M i le the prevalence of

alcohol related birth d8f8Cts (FAS plus Partial FAS) ranges from 51 to 101 per

1 000 children.

The dysrorphology parameters which differ signifcantly behween the

alcohol exposeâ and unexposed gmups are: decreased height, weight head

circunrfmce and palpehl fissure lengths, and mi- hypoplasia.

Growth parameter data of the "Normal" categocy of schod-aged children

were used to generate standard Native growth curves for school-aged children

from this community. These wrves wwe compared to the preem'sting curves in

the Merature, primarily derïved using Caucasian data. and showed signifiant

differences betwwn the two populations. With respect to postnatal growth,

Native children from this cornmunity tend to be heavier, taller, have larget head

cirwmfwences, longer fingers, and more widely spaced eyes than their

Caucasian wunterparts. Cornparisan of the FAS and Partial FAS children with

the Native curves, increased the number of children that would be considered

"classic" F AS cases, as opposed to cornparisons against Caucasian standards.

iii

- I would like to take the opQortunity to thank a nurnber of people without

whom I could not have completed this pf@8Cf-

First, to the Chief and Band Council, Community, school. and teachen - Thank you for your support in this project, and for allwng us into your homes

and schod. Thank you to B.C., L.O., L.C.. S.S., G-R-, ER., and L.S. for their

help in the local organization and e x d i o n of this project. Special thanks to

AG. for her enthusiasm, support, and total cornmitment to the pro~ect. Without

the help of these individuals at the local level, it would not have been possible to

cany out this study.

Secondly, I would like to thank my Cornmittee - Dr. J.A. Evans and Dr.

M.E.K. Moffatt for their patience, words of wisdom, guidance and support over

the past tw years. I have leamed a great deal from you both - Thank you!

To my advisor - Dr. AE. Chudley ... first, I must thank you for arousing

my interest in FAS. You have been a great help over these past t h e years. I

appreciate al1 the driving (on data collection days), time, Mort, patience and

guidance you have shared with me. Your encouragement and support have

helped more than I can express.

Thanks to Mary Cheang for all her assistance with the statistical aspeds

of the study, and to Lou Frederick, Kathy Bell, and lnez Mitchell for their various

assistance with aspects of the project

Thank you to my fellow Graduate Students (both here, and colleagues

abroad), for your Iistening ears, kind mxds, tedinical adviœ and support!

And last but not least - to my Family, who were a h y s there for the good

days and the bad days, for their shoulders and their Iistening eam. Thanks to my

sister, Jennifer, for her willingness to share her secretanal skills, and a fw good

laughs when the stress levels were ninning high. Thank you Mom and Dad, for

providing me with room and bard, far putting up with my mood swings, and for

your general care and concem. I cauldn't have corne Ulis far without your love

and support.

This research project was supported in part by a grant from the

Children's Hospital Researdi Foundation (Winnipeg, MB) and by a research

grant received from the Canadian Pediatric Society Cornmittee on lndian and

Inuit Health.

. Abstract ....................................................... ii

Adviawledgments ............................................... iv

Table of Contents ............................................... vi

List of Figures ................................................... ix

ListofTables .................................................. xii

List of Appendices .............................................. xvi

1.Olntroduction ................................................. 1

................................... 1-1 Abhot use and abuw 1

1.1 -1 Demographics of Women who abuse alcohol ........... 4

1.2Teratogens ............................................. 5

1.3 What is Fetal Alcohol Syndrome (FAS)? ..................... 6

1 -4 Effeds of Alcohol on the Developing Fetus .................. 15

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 .4.1 Growth Retardation 15

1 .4.2 Craniofacial Dysmorphology ....................... 16

............................ 1 .4.3 Skeletal Abnomalities 17

1 .4.4 Other Physical Anomalies associated with FAS . . . . . . . . 17

1.4.5 Central Newous System Impairment ................. 18

(1 ) Behavioural Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

(2) Cognitive Difficulties . . . . . . . . . . . . . . . . . . . . . . . . . . 20

(3) Structural Abnormalities . . . . . . . . . . . . . . . . . . . . . . . 21

.................................... 3.1 -3 Prevalence 67

................................. 3.2 Dysmorphology Results 71

................................. 3.3 Nonnative Data Results 80

4.0 Discussion ................................................ 91

.......................................... 4.1 Epidemiology 91

.................................. 4.1 -1 Alcohol Abuse 91

............... 4.1.2 Prevalenœ of FAS and Partial FAS 95

....................................... 4.2 Dysmorphology 98

....................................... 4.3 Normal Curves 103

4.4 Possible biological models for increased observation of FAS among

. . . . . . . . . . . . . . . . . . . . . . . . . . . . F i ~ t Nations Cornmunities 109

....................... 4.5 Significame of this body of research 112

............................... 4.6 Further Research Topics 114

................................................. APPENDICES 116

Referenœs ................................................... 187

viii

Figure 1. Diagrammatic representation of the characteristic craniofacial features

0fFAS. ...........................*.......*............. 10

Figure 2. Diagrammatic repmsentaüon of the aitical periods in human

developrnent. ............................................ 26

Figure 3. Diagrammatic representation uf traniofacial landmarks measured as

part of the Dysrnorphology Assessment section of the Community FAS

study. .................................................. 52

Figure 4. Graphic representation of the number of births per year of the cohort,

number of exposures to alcohol per year and number of children bom

.................. with FAS or Partial FAS per year of the cohort -66

Figure 5. Graphic representation of the possible range of prevalence rates of

FAS, Partial FAS, and combined FAS and Partial FAS in the study

Cornmunity (per 1000 children). .............................. -70

Figure 6. Normal Native Male Height Curve, derived from data colledeci on 74

................................ Normal males (ages 5 - 15). 135

Figure 7. Normal Native Female Height Curve, derived from data colledecl on 59

Normal fernales (ages 5 -1 5). ............................... 137

Figure 8. Normal Native Male Weight Curve, derived from data colleded on 74

Normal males (ages 5 - 15). ................................ 139

Figure 9. Normal Native Female Weight Curve, derived from data collected on

59 Normal females (ages 5 -1 5). ............................ 141

Figure 10. Normal Native Male Head Cifaimference Cunre, derived from data

colleckedon74Nomial males(ages5 -15). ................... 143

Figure 11. Normal Native Female Head Circurnferenœ Curve, derived fmm data

coîlected on 59 Normal fernales (ages 5 -1 5). .................. 145

Figure 12. Nonnal Native Male Palpebral Fissure Length Curve, derived from

................ datacollededon74Nomial males(age5- 15). 147

Figure 13. Nomal Native Female Palpebral Fissure Length Cuwe, denved from

data allected on 59 Normal females (age 5 - 15). ............... 149

Figure 14. Nomal Native Male Philtnim Length Cuwe, derived from data

c o l l ~ e d o n 7 4 N m a l males(age5-15). . . . . . . . . . . . . . . . . . . . . 151

Figure 15. Normal Native Female Philtrum Length Curve, derived from data

collected on 59 Normal females (age 5 - 15). ................... 153

Figure 16. Normal Native Male lnner Canthal Distance Curve, derived from data

collededon74Nmal males(age5-15). .................... 155

Figure 17. Nomial Native Female lnner Canthal Distance Cunre, derived Rom

............... data colleded on 59 Normal fmales (age 5 - 15). 157

Figure 18. Normal Native Male Outer Canthal Distance Curve, derived from

data colleded on 74 Normal males (a* 5 - 15). . . . . . ............ 159

Figure 19. Normal Native Female Outer Canthal Distance Cuwe, derived f i m

data collected on 59 Nomal fernales (age 5 - 15). . . . . . . . . . . . . . . . 161

Figure 20. Normal Native Male Hand Length Curve, derived from data colleded

on 74 Normal males (age 5 - 15). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163

Figure 21 . Normal Native Female Hand Length Cwve. derived fKMi data

cdlededon59Nomlfemales (age5.15) .................... 165

Figure 22 . Normal Native Male Palm Length Cwve. derived from data collected

o n 7 4 N m l males (age5.15) ............................. 167

Figure 23 . Normal Native Female Palm Length Curve. derived from data

collected on 59 Normal fernales (age 5 . 15) .................... 169

Figure 24 . Normal Native ON0 Angle Cuwe. defived from data colledecl on 133

Normal children (pooled sex data) (age 5 O 15) . . . . . . . . . . . . . . . . . 171

LbumBkm

Table 1. N w Diagnostic Criteria for FAS and Alcohol Related E M S as

suggeated by the Institute of Medicine (1 996). ...-............... 13

Table 2. Summary of some of the available data on the Prevalence and

Incidence rates of FAS and Partial FAS. .....-.................. 35

Table 3. The TWEAK Questionnaire.

........................................................ 47

Table 4. Aicohol Exposure Data. ................................... 60

Table 5. Break dom of the Birth cohort, to illustrate exposure levels per year of

birth, and numbers of FA$ I Partial FAS cases per year d bnth- ..... 60

Table 6. Breakdom of study sample by diagnostic classification categories

based on the dysmorphdogy assessrnent only (Dx) and based on full chart

review ( NDx). ............................................. 64

Table 7. Range of Prevalence (per 1 ûûû children) for FAS, Partial FAS, and

Combined ARBD in this study community. . ..................... 68

Table 8. Results of Chi Square and Student t-test analysis of Dysmorphology

. . . . . . . . . . . Parameters in Exposeci versus Non-exposed Individuals. 73

Table 9. Results of Chi Square and Wilcoxon Sums Rank analysis of

Dysmorphology Parameters in lndividuals with graded alcohol exposures

(no exposure versus low exposure verws high exposure). .- . . . . . . . . 73

xii

Table 10. Comparison of Dysrnorphology Parameters by Diagnostic Categories

based on the results of the Dysrnorphology Assessrnent alone, and the

-on of individuals with akiormol fwtures per categary (qualitative

data), or mean percentile rank per category (quantitative data). ...... 74

Table 1 1 . Results of the analysis of the dysmorphology parameters by New

Diagrmis based on dysmorphology assessrnent and hill chart review.

and the proportion of affeded individuals per category (qualitative data)

or mean percentile rank scores per category( quantitative data) ...... 78

Table 12. Comparison of exposed and non-eqmsed, as well as the cornparison

of graded level of alcohol exposure subgroups within the "Normal"

diagnostic category, with respect to borddine staüstically significant

morphometric parameters. .................................. 79

Table 13. Mean percentile rank scores mesponding to the borderline

statistically signifiant (0.01 r ps0.05) morphometric parameters identified

during analysis of the parameters by exposure versus no expsure and

graded levels of alcohol exposure in the "Normal" diagnostic category.

. . . . . . . . . .*.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

Table 14. Student t-test (Wtailed) analysis results for comparing the means

behnreen the Iwo sexes for each of the morphomettic parameters.

........................................................ 81

Table 15. Results of the P aired Student t-test comparing the medians of the

Normal Cauaisian growth ames to that of the new generated Normal

xiii

Native growoi wwes (for each sex). . . - - . . - . - . . . . . . . - . . - . . . . . . . 85

Table 16. Coinparison of Height, Weight and Head Cirwmference of FAS and

Partial FAS Individuals, between Caucasian and Native N m a l Standard

Cuwes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Table 17. Cornparison d lnner Canthal Distance, Outet Canthal Distance, and

Palpebfal Fissure Lmgh of FAS and Partial FAS Individuals. between

Caucasian and Native Nonnal Standard Curves. . . - . . . . . . . . . . . . . 87

Table 18. Comparison of Philtrum, Palm and Hand Lengths of FAS and Partial

FAS Individuals. between Caucasian and Native Nonnal Standard

Cunres.

........................................................ 88

Table 19. Comparison of ON0 angles of FAS and Partial FAS Individuals,

between Caucasian and Native Normal Standard Cunres. . . . . . . . . . . 89

Table 20. Comparison of the number of Individuals with "Abnomal" Percentile

Ranks between FAS ami Partial FAS data plotted on Caucasian versus

Native Normal Growth Curves. . . . . . . . . . . . . . . . . _ . - . . . . . . . . . . . - 90

Table 21 . N m a l Male Height Data . - . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 72

Table 22. Nomal Female HeigM Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

Table 23. Normal Male Weight Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

Table 24. Nonnal Female Weight Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

Table 25. Normal Male Head Circumference Data . . . . . . . . . . . . . . . . . . . . 174

Table 26. Nonnal Female Head Circumferenœ Data. . . . . . . . . . . . . . . . . . . 174

xiv

...................... Table 27 . Nonnal Male Palpebral fissure length 175

.................... Table 28 . N m a l Fernale P alpebral fissure length 175

Table 29 . Normal Male lnner Canthal Distance .. .. ................... 176

Table 30. Nomial Female lnner Canthal Distance ..................... 176

...................... Table 31 . Normal Male Outer Canthal Distance 177

Table 32- Nonnaf Fernale Outer Canthal Distance ............. .. ..... 177

............................ Table 33 . Normal Male Philtmm Length 178

........................... Table 34 . Nomial Female Phihm Length f78

............................... . Table 35 Normal Male Palm Length 179

............................. Table 36 . Nomal Female Palm Length 179

............................... . Table 37 Normal Male Hand Length 180

............................ Table 38- Normal Female Hand Length 180

. . . . . . . Table 39 . Normal ON0 Angles (male and female wmbined results) 181

Appendix A. Consent fotms useâ in the FAS Community Study on one First

Nations Comminity in Manitoba. ............................. 1 17

Appendix B. Matemal Interview fom used in the FAS study of one Manitoba

First Nations Community. ................................... 122

Appendix C. Hospital Records Review Fom used to collect data frorn each

................. childs hospital records at their hospital of birth. 128

Appendix D. Physical Examination fom used during the Dysmorphology

............... Assessrnent aspect of the Community FAS study. 130

Appendix E. Normal Native wrves (Figures 6 - 24) and their corresponding data

tables (Tables 21 -39 ). .................................... 133

Appendix F. Data used to compare the medians of the Caucasian wrves versus

the newly generated Native Curves. .......................... 182

1.0 Inmction

The following introduction is intended to provide the reader with some of

the relevant background information on the subject of Fetal Aicohol Syndrome

(FAS). it wili cover the areas of alwhol use and abuse, with special referenœ to

women, examine alcohol as a teratogen on the devaloping fetus through

examination of various animal model studies, provide an historical account of

FAS. detail criteria for FAS diagnosis, and review the available epidemiological

data wnceming FAS with special reference to Aboriginal epidemiology reports.

F inall y a review of aie thesis and its hypotheses will be provideci.

c Alcoholism is a growing wnœm in our society with the number of women

abusing alcohol inaeasing steadily. In fact, during a five year period spanning

1973 to 1978 the number of women alcoholics in Canada increased from 90,000

to 400,000, and over the past twenty yean the ratio of male to female alcoholics

in Canada deaeased frorn 8: 1 to an equal distribution of 1 : 1 (Persaud, 1 990).

According to Golbus (1980), alcoholism is the most cornmon dnig abuse problem

today affecting 1.2% of women of childbeafing years. Other survey studies

conduded in the United States conduded that as many as 10% of women of

child bearing years are considered to be risk drinkers, that is these women

consume on average greater than one drink per day (Dufour et al, 1994).

Recent research has shown that this trend maybe slowing d m , as small

decreases in the number of women dnnkers are beginning to be observed.

According to the 1995 Canadian Profile on the use of alcdial, tobacco and other

dnigs by Canadians, in 1993 the number of Canadians (aged 15 years and

older) who reparted drinking was 74.4%, a small deaease as compared to 79%

in 1990. These statistics al= state that the highest drinking rates are k i n g

found among yang Canadians behween the ages of 15 and 24, and that the

type of drinking reported is most often "binge-drinking" (consumption of five or

more dtinks on any one occasion). Wth respect to seIf-report, men tend to drink

twice as much as women (5.9 drinks at a time versus 2.3 drinks respedively).

However, it is possible that the estimate for women may be low, sinœ women

are less likely to report problems relating to their drinking (1 1.9% men versus

6.2% women). Low income Canadians tend to report drinking as being more

problematic Vian when wmpared with their high income counterparts (1 7.9%

versus 7.9 % respectively) (Canadian Centre on Substance Abuse, 1995).

The Canadian figures indicate that although overall consumption and

reporting of afcohol problems has decreased slightly over the past 5 years, it is

our youth, our next generation, that still are reporting the highest alcohol use

figures. The figures dted are alanning given that alcohol has been identified as

a teratogen, causing varying degrees of congenital malformations and mental

retardation in infants (Weiner et al, 1989).

Several studies have been conduded over the years to detemine

woments awareness of risk drinking during pregnancy. Serdula et al (1991 )

conducted a seif-report survey of m e n during the years 1985 to 1988 to

examine trends of alcohol consumption in pregnant women. They found a

decrease in the number of women who consumed alcdiol while pregnant over

this time perïod, fmm 32% in 1985 to 20% in 1988. However, of those

individuals who did drink during pregnancy, no decrease in the median number

of drinks consumed per month was obsenred. They also point out that, although

there was an overall decrease in the consumption rate of alcohol while pregnant,

there was no signifiant deaease observeci in ywng (less than 25 years of age)

pregnant women, or in those who were l e s educated (high school or less).

ûther studies have been conducted reœntly conœming awareness of the

risks of heavy drinking and FAS in adults (Dufour et al, 1994) and in youths

(McKinnon et al, 1995) in the United States. 60th studies indicate that

knowledge with respect to the risks of drinking during pregnancy is high (89% to

92% in the adult study versus 81 % in the youth study) (Dufour et al, 1994;

McKinnon et al, 1995). Also of interest, approximately 73% of adult wornen

versus 72% of youths surveyed have heard of FAS. Unfortunately, only 39.0%

of adult women and 46.9% of youths studied could conectly define FAS. In the

study by McKinnon et al (1995), 47.8% thought that FAS was a baby bom

addicted to alcohol. An encouraging number of youths (95.0%) wrrectly

believed that FAS is a preventable disorder. Hawever, figures suai as 50.3%

believing FAS is curable, and 48.5% believing FAS is inheritable illustrate that

sbonger efforts must be made to ensure that FAS is acairately understood by

the general population, More prevention can m i n .

1.1 .l [kmographics of Womm who abuse alcohd

According to epidemiological studies on the demographics of women who

abuse alcdrol, those wwnen who drink heavily tend to be young, white, single,

have higher edwation (greater than high schod) and imome, and work full time

outside of the home (Day et al, 1993). Women who abuse alcohol dufing the

first trimester of pregnancy can also be generally identified by these nsk factors.

However, these factors do not hold tnre and do not identify those women who

abuse alcohol throughout pregnancy- Aecording to Day et al. (1993), women

who continue to drink in the third trimester more &en tend to be older, black,

less educated, lower socioeconomic status (SES), have more Iife events, and

use other illicit drugs. Sokol et al (1 980) reported similar findings, that older

multigravidas, who were unmamed, were more likely to drink and abuse other

dmgs (bai cigarettes and illicit dnigs) during pregnancy. These women were

also more likely to be dinically recognized to have psychosocial problerns and

as having a higher frequency of previous first trimester spontaneous aôortions.

low-birth weight infants and infants congenital anomalies, in cornparison

with a non-alcohol abusing control group (Sokol et al, 19ûû). A recent study on

the charaderistics of a group of Canadian women who engaged in binge-

dn'nking also reinforces the prototype of those women who engage in fisky

drinking patterns as being younger, single, Caucasians, who smoke and tend to

use illicit drugs, more &en than their non-binging counterparts (Gladstone et al,

1997) . However, this stuây is limited as subjects were pfimarily af Caucasian

background and were seleded based on self r8ferral to a cainselling agency. - Teratology is the science that focuses on abnonnal prenatal development

including congenital fetal anomalies (Moore and Persaud, 1993). This brandi of

science examines both genetic etiologies (such as genetic inheritanœ, or

chromodomal abberations) of birth def8ds as well as potential environmental

factors which contribute to abnomal phenotypes obsenred in children. It might

be assumed that the period be-n conception and birVi would be a safe time,

the child is shielded from the outside world and al1 its pollutants. However, is

this environment as safe as we may Iike to believe? Studies are now showing

that the womb is not the safehouse we once thougM it was, as the unbom child

can be exposed to many hamiful agents which traverse the placenta and can

cause a range of possible efFects on the fetus, including both major and minor

malformations, mental retardation, and death in some instances. These

environmental agents that induœ fetal damage following matemal exposure to

them during the pregnancy are knomi as teratogens. Some teratogens include

drugs (both prescription and street drugs), radiation, viruses, and almhol

(Zimmeman, 1991 ).

1.3 What is Fetal Aicohol -me (FASE

Suspeded teratogenic M8ds of aicohol date back to biblical tknes. In

the Bible, Judges 13: 34, there is a waming that states "...you will soon be

pregnant and have a son. Take care not to drink any wine or ber" (Good News

Bible, 1976). During the gin epidemic in England during the early mid

eighteenth œntury physicians noted that the children of alcoholic parents tended

to be Weak, feeble and distempered" (Sokol, 1981 ). Even within the Amerindian

culture, wamings wnceming alcohol use and pregnancy were express&.

According to some Navajo elders "...if a woman about to bear a child drinks

aazy water, the newbom will be crazy in the body and the mind" (The Navajo

Tribe" in Streissguth el al, 1988). Despite al1 of the historical suspicions,

evidence confiming such wamings was not available until more recently. It has

sinœ b e n shown that many mothem who are chronic abusers of alcohol during

pregnancy deliver children with a unique dysmorphic phenotype (Lernoine et al,

1968; Jones et al, 1973; Jones and Smith, 1973). First daaimented by Lernoine

et al (1968) in France and independently observed by Jones et al (1973) in the

United States, this unique phenotype, which includes central nervous system

(CNS) dyshrndion, growth deficiency, and craniofacial dysmorphology, came to

be known as Fetal Alcohol Syndrome (FAS) (Jones end Smith, 1973)

To date there is no single test available that can positively identify

children who are M8Cfed with fetal alcohol syndrome (Osborn, 1993). Due to

the great variability in types of abnormalities and severity of the anomalies

obsenred in children exposeci in utero to alcohol, fetal alcohol syndrome (FAS) is

diffiwlt to diagnose (Clarren and Smith, 1978; Clarren, 1981 ) However,

diagnostic criteria have been suggested by the Research Society on Alcoholism

(RSA) in order to help simplify this ta~k . The aiteria for FAS diagnosis are

based on a cluster of abnormalities that have been cited in nearly al1 cases of

FAS dating back to the first reports by Lemoine et al, and Jones et al. The first

important piece of information required before such a diagnosis can be made is

a positive history of materna1 alcohol abuse during the pregnancy (Osborn et al,

1993; Aase, 1994). Following that, the minimal criteria for FAS diagnosis are as

follows:

(1 ) prenatal andor postnatal growth deficiencies, which include height,

weight, and / or head ciramference below the tenth percentile when

co~8Cfed for age.

(2) central nervous system (CNS) impairment, includ ing developmental

delay, behavioural disturbances such as Attention Deficit Disorder (ADD)

and Attention Deficit Hyperadivity Disorder (ADHD) (which include

impulsiveness, poor attention and concentration, and hyperadivity),

intelledual impairment (mental retardation), andor signs of other

neurolog ic abnormal ity (structural or otherwise).

(3) characteristic maniofadal dysmorphology with at least hnro of the

following signs: rnicmcephaly, (head cirwrnferenœ below the third

perœntile when m8dd for age), microophaialmia and for short

palpebrel fissures, poorly developed phiitrum, thin upper lip and

flattening of the maxillary area (Clarren and Smith, 1978; Rosetî,

1980; Osôom et el, 1 993; Spohr et al, 1993). Figue 1 illustrates

these characteristic craniofacial abnormalities of the FAS face

Some childen may not exhibit al1 the required criMa for FAS diagnosis.

However, they may still have positive histories of heavy matemal alcohol

consumption during pregnancy and may exhibit only behavioural or cognitive

diffiwlties andor other nonspecific anomalies associated with the syndrome.

mese diildren are said to have a milder fom of FAS known as Fetal Alcohol

Effect (FAE) or Alcohol Related Bi* Def6cts (ARBD) (Coles, 1993; Committee

on Substance Abuse and Committee on Children with Disabilities, 1993; Spohr,

1 993).

Alcohol is not unique in causing each of the previously mentioned signs

and syrnptoms (Rosett, 1980). What does seem to be unique is the dustering

of this subset of non-specific anomalies when a fetus has been exposeci to high

levels of akohol in utero - the diagnostic criteria for full bfown FAS (Clarren,

1 981 , lnstitute of Medicine, 1 996). FAS is the tip of the iceberg - the severe

extreme of a variable continuum of "possible fetal alcohol effeds". Thus it has

been suggested that any syrnptoms falling short of the minimum required criteria

Figure 1. Diagrammatic representation of the characteristic aaniofacial features of FAS. (Modifiecl from: Chudley, 1991 )

for FAS should not be considered as a separate and unique diagnosis of FA€.

lnstead FA€ stxwld be used in r e f m c e to the consideration that alcohol is a

possible cause of the patient's birth defeds (Osbom et al, 1993; Aase et al,

1 995).

Sinœ the time that the Research Society on Alcoholisrn set forth its

minimum aitetia for FAS diagnosis, a new diagnostic dessification systern has

been suggested by the lnstitute of Medicine (1996). The new diagnostic criteria

and diagnostic categories set forai by the lnstitute of Medicine is outlined in

Table 1.

In this new five level classification system, the lnstitute of Medicine (1 996)

has atternpted to provide a more accurate classification system. by ensuring that

diagnostic aiteria are reliable, and valid. Category number one in the new

system is the dassic FAS diagnosis, as before. ln the Instituters new

classification system, the term FAE as a uniquediagnosis separate to that of

FAS has been removed and been replace by the tenn "Partial FASg'(category

number 3 ). A second prime difference between the old classification system

and the newly describeci one, is that the InstiMe of Medicine acknowiedges that

one of the primary diagnostic criteria of the past for FAS - evidence of alcohol

exposure during the pregnancy, is one of the most difiicult to attain. Reasons for

the difficulty in attaining acairate information regarding alcohol exposure

histwi-es range from the fact that some adoptive mothers may not know the

alcohol history af their adopted chilci's prenatal life, while m e mothers may

have difficulty remembering from a past pregnancy, and, in some cases, alcohol

intake maybe denied for fear of stigmatization. For this reason, even if alcohol

exposure cannot be confinnecl, but the child illustrates al1 the phenotypic signs

of FAS as assessed by an em8110Bd dysmorphologist, FAS classification can

still be made under category number 2 of the new system. The fourth and ffth

categories represent a dustering of dinical conditions with confimeci alcohol

exposure that is thought to be linked to the obsetved conditions. Category four

represents a list of physical def8ds or congenital anomalies that indudes

malformations and dysplasias and is temed Alcohofielated Birth Defects

(ARBD). while category five, Alcohol-related Neurodevelopmental Oisorder

(ARND), represents neurodevelopmental abnormalities and complex behaviour

or cognitive ahmnalities that cannot be explaineci by family background or

environment alone. It is possible for both category four and category five to w-

ocwr and thus should be stated as so, if the situation presents itself.

The anomalies associated with FAS are not unique to teratogenesis by

alcohol. Many syndromes and other drug exposures have been found to present

with similar anomalies. However, close examination will reveal to the trained

e ye that, although these syndromes illustrate growth deficiencies and facial

anomalies, they are distinct fram FAS (Institut8 of Medicine, 1996). Some

syndromes which have been confused with FAS in the past include: Aarskog

syndrome, Williams syndrome, Noonan syndrome, Dubowitz syndrome, Bloom

syndrome, fetal hydantoin syndrome. maternai PKU fetal effeas, and fetal

Table 1. New Diagnostic Criteria for FAS and Alcohol Relatecl H h t s as suggestd by th. Imütute Or M d c h (1996).

1 1. FAS with conlknrd muteml akohol erpown

II B. Evidence of charaderisoc pattern of facial anomalies such as short palpebral fissures, flat upper lip, flattened phibum. and fat rnicibce

C. Evidence of growîh retardaüon in at least one of the following: - low birth w e @ M f;or gestaaonal age - deceleraüng weight over time not due to nubition - di iport ional low weight to hdgM

D. Evidence of CNS neurodevelopment8l abtiorrnalities in at le& one of the followïng: - decreased cranial site - structural m i n abnormalities such as microcephaly, partial or complet8 agenesis of the corpus callosum, cerebellar hypoplasia

- neurological hard or soft signs (as age appropnate) such as impaired fine motor skills, neurasensory hearinq loss, poor tandem gait, poor eye-hand coordinalion

Il 2. FAS without confinnad mtmnrrl rlcohol exposun

Il 3. Parthl FAS with confirmed matenul rlcohol expsuiis

A. Confimed matemal alcahol expasure B. Evidence of some componenls of the pattern of characteristic facial anomalies Eithar C, D, or E C. Evidence of growth retardation in at least one of the followhg:

-low bitth weight for gestational age decelerab'ng weight over tïme not due to nutntion disproportional low weight to height

O. Evidence of CNS neurodevelopmental abnormalities in at least one of the follwing: decreased cmnial site -structural braim abnonnalities such as microcephaty, parhl or completet agenesis of the corpus callosum, cerebellar hypoplasia

-neurological hard or soft signs (as age appropriate) such as impaired fine motor skills, neurosensory hearing loss, poor tandem gait, poor eye-hand coordination

E. Euüence of a cornplex pattern of behaviour or cognitive abrionalioes that are inconsistent mth developmental level and cannot be explaineci by family background or environment alone, such as learning diutties; deficits in school performance; poor impulse control; proMems in social perception; deficig in higher level receptNe and expressive language; poor capacity for abstraction or metacognition; specific deficits in mathematical skilk; or proMems in memory, attention. or iudarnent

Clinkal conditions in which then is a history of matmu1 rkohol expoium and where dinical or animal research has liiked matemal alcohd ingestion to an observeci outcorne

4. A k o h o h ~ bnth dmhds [ARBD) Cardiic: Atrial seml def;ec&, ven@kular septal defiMs, aberrant great

vesseîs, Tetraiogy of Fallot Skeletal: Hypopiadk nails, clinodactyîy, shoRened îiRh digits, pectus

excavatum anâ carinatum, radiiulnar syno9tosis, W i l - Feil syndrome, flexion contractures, hernivertebrae, cam@oâactyly, s c o l i i

Renal: aplastic, dysplastic, hypoplastic Wneys, horseshoe kidrieys, ureteral duplications, hydronephrosis

Ocular: Strabismus, refradw probiems secondary to maIl globes, retinal vascular anomalies

Audiiory: Corrducüue hearing lm, neurosensory hearing lasg ûther. Virtuslly every malformation has been described in some patient

with F AS, The etiologic specMly of most of these anomalies to alcohol teratogenesis remains uncertain.

Presence of : A Evidence of CNS neurodevelopmental abnormsîi i in at least one of the following:

- decreased cranial sire - structural brain a b n o m a l i such as microcephaly, partial or compfete agenesis of the corpus callosum, cerebella? hypoplasia

- neurological hard or soft signs (as age appropriate) such as impaired fine motor skills, neuroçensary hearing loss, poor tandem gait, poor eyehand coordination

and/or E. Evidence of a cornplex pattern of behaviour or cognitive abnormal i that are inconsistent

mth developmental level and cannot be ewplained by hmily backgtourid or environment alone, such as learning diniculties; defià(s in school performance; poar impuke control; proMems in sacial perceptian; dekits in higher level receptive and expressive language; poor capacity for abstraction or me&acognilian; specific deficiEP in mathematical skilk; or problerns in rnemory, a t t e n l b n . o r ~ n t - __ - Trom InstiMe of Medicine (1 996), used with permission.

toluene syndrome (Institute of Medicine. 1996).

1 A.1 Gnnivth Retardaion

Prenatal andlor postnatal growai fetafdation is one of the primary criteria

in an FAS diagnosis. Children whose rnothers were dwonic abusers of alcohol

throughout their pregnancy tend to sutfer from symmetric growth âeficiency,

induding weight, height (both below the tenth percentile for age or gestational

age), as well as head cirarmf&enœs bekw the third percentile (Jones et al,

1 974; Cole, 1 993; Spohr et al, 1 993). Studies have illustrated the association of

prenatal alcohol exposure with significantly lower birth weights in children (Jones

et ai, 1 974; Little, 1977; Mills et al, 1984). Little (1 977) suggests that alcohol

exposure late in pregnancy will have a greater M8Cf in deaeasing birth weight

than the same level of exposure early in pregnancy.

Despite adequate nutrition dunng postnatal life, the growai retardation of

FAS affecteci individuals persists especially with respect to height and head

cirwmferenœ, as bath parameters tend to remain well below average

throughout life (Streissguth et al, 1991 ). It has been suggested that the slow

growVi in heaâ ciraimferenœ is an indicator of slowed bain growth, which tends

to be a consistent feature in FAS affected individuals (Aase, 1994). The weight

parameter differs slightly from the other hwo parameters in that a greater level of

catch-up growth is obsenred. It has been found that, on average, males will

show some level of catch-up with respect to weight, but more dramatic catch op

is noded in pubescent fernales, who have been said, in m e reports, to become

moderately obese during late adolescence (Streissguth et al, 1 991 ; Spohr et al,

1 993).

Craniofacial abnonnalities are probably the most readily observable

features of FAS. S o m of aie hallmark features of FAS facies are: short

palpebral fissures which may give the illusion of the child's eyes k i n g smaller

and fumer apart than normal; hypoplastic miciface; and long smooth philtmm

with poor Cupids bow formation and thinned upper lip (Aase, 1994). Other

craniofacial anomalies associated with prenatal alcohol exposure include:

epicanthus, strabismus and ptosis, with respect to eye anomalies; short

uptumed nose with anteverted nares; m icrognathia; minor ear anomalies

induding lm set posteriorly rotated ears and lop ean; high arched palate and

cleft palate (Church and Gerkin, 1988; Autti-Ramo et al, 1992; Spohr et al, 1993;

Aase, 1994).

According to longtemi follaw up studies, unlike the growth parameters, the

distinctive aaniofacial features of F AS tend to dissipate with time (Streissguth et

al, 1991 ; Spohr et al, 1993). Streissguth et al (1 991 ) report that increased

growttr of Vie nose, chin and midlace, along with thickening of the philtral ridges

during adolescence dramatically changes the overall facial appearance in many

patients. Hawever, even in the older patient, relatively short palpebral fissures,

smooth phiitrum and thin upper lip can be important discriminating features.

1.4.3 Skeletal Aimonnalities

Prenatal alcohol exposure has besn associated with inaeased frequency

of some nonspecific siceletal akiamialities, although these are l es consistent

than the cardinal FAS features. Some of these abnomalities include

camptodactyly, climdactyly, limited joint movement (such as incomplete rotation

at the elbow) and abnormal dennatoglyphics (such as longitudinally oriented

palmar creases) (Streissguth et al, 1991 ; Spdw et al, 1993; Aase, 1 994).

According to Spohr et al (1993), signifiant improvement of skeletal anomalies

with time was obsewed. H0w8verI Streissguth et al (1991 ) cite that these minor

anomalies rernain important discriminating charaderistics in older FAS patients.

1.4.4 Ww Phyrical Anomalies .uociatd with FA$

-sure to alcohol in utero increases a childs chance of k i n g M8Cfed

with a number of nonspecific anomalies. Some of the more cornmon, although

still not consistent, anomalies include: congenital heart defeds, minor extemal

genital anomalies, renal defects, hemiae, hemangiomata and spina bifida (Spohr

et al, 1993; Aase, 1994). It has been stated that these anomalies ocair up to 5

to 60 times more oftm in childm who have been exposed to alcohol prenatally

than in the general pediatric population (Aas8, 1994). Other studies have

suggested an association bebmen prenatal alcohol exposure and hearing

dimders sudi as bilateral recurrent mous otitis media and bilateral

sensonneural hearing loss, as well as a high incidence of speech and language

disorders (Church and GMn, 1988). The speech of children with FAS has

been desaibed as being slurred, guttural, dysarthric and monotorous, and

approximately 90 percent of di i ldm with FAS will deronstrate delays in both

reoeptive and expressive language development (Lewis et al, 1994). Dental

abnormalities have also been observecl in patients with FAS (Coles, 1993).

1.4.5 Central Necvous System Impairniant

(1) BehavioumI HfWs

One of the most striking symptoms of prenatal almhol exposure is its

effect on the developing central nervous system. Shortly Mer birth exposed

infants illustrate behavioural deficits such as initability, apparent hyperawsis,

poor su& reflex and sleeping disturbanœs (Clarren and Smith, 1978; Clarren,

1981 ; Forrest el al, 1992; Lewh et al, 1994). One study noted a dose-

dependent deaease in infant reaction time in infants exposeci to alcohol in utero

(Jacobsen et al, 1994). During the preschool period, FAS children have been

desaibed as being aftectionate, distradible and very adive, with poor fine motor

coordination, mild cerebellar dysfundion and hypotonicity also being cornmon

(Clarren and Smith, 1978; Clamin, 1981 ; Aase, 1994, Lewis et al, 1994).

It is during school ages that the behavioural deficits in these diildren may

cause problems. Studies have s h m mat one of the mOSt common problems in

children exposed to alcahol in utem is attention def~cit disorder (ADD), attention

deficit hyperactivity disorder (ADHD), and lmming disabilities (Ouellette, 1985;

Aase, 1994) Nat only has chronic alcohol abuse been Rnplicated in these

disorders, but signifiant leaming proMems have been assodateci with binge

drinking (consumptim of five or more drniks on any occasion) during pregnancy,

as well (Forrest et al, 1 992). It has been suggested that these difficulties in

leaming may be associatecl with deficits in organiration and prodessing aspects

of information input, output, integration and memory. It is for these

reas~nS-Short attention span, hypgractivity and deficits in information

organization and processing-that aiese children have problems with traditional

means of ducation, and create a challenge for the educabf to set up programs

in a context-specifc manner in order to teadi the affect4 diild (Weiner and

Morse, 1994).

Affected adolescents and adults do not out grow these behavioural

problems. In fact, adult patients have been said to have maladaptive behavioun

which make them unsuitable for traditional job training programs (StreissguM et

al, 1 991 ). Attentional defcits, poor concentration, corn prehension and

judgement problems persist throughout adulthood. As well, problems with

conduct becorne an issue, such as lyhg, defiance, and lack of consideratiofi for

othen (Streissguai et al, 1 991 ). Recent studies have illustrated that it is not just

FAS affecteâ individuals who are at risk for these sscondary disabilities.

Individuals with FAE (Partial FAS) have been noted to have increased rates of

secondary disabilities sudi as dmpping out of school, and being in trouble with

the law, wmpared to their FAS cainterparts (StreissguVi et al, 1 996).

(2) Cogmve DtQlicultieS

Mental retardation has b e n cited as one of the most çomrnon and

serious Meds of prenatal alcdiol exposure on the developing fetus (Clarren

and Smith, 1978). me more phenotypicaliy severe patients were the ones who

also had the lower IQs, wgeesting that the lower intelligence is an Med of the

alcohol exposure and not due to the postnatal environment of the child

(Streissguth et ai, 1978). Even in adulthood, lower intelligence persists. A

fol lw up study of FAS-FAE patients by Streissguth et al (1 991 ) noted the mean

group IQ to be 68, whiai just falls into the mentally retarded range of IQ scores,

with scores ranging f m 20 (sevwely retarded) to 105 (normal). The normal

scores were in the minotity with approximately 58% of the scores being 70 or

lower. FAE individuals showed, on average, 10 point higher IQ scores than their

FAS cwnterparts, suggesting that alcohol dose may be an important factor in

the severity of mental retardation. FAS aff8Cfed adults and adolescents in this

study frequently exhibited ariaimetic deficits (second grade level), and

significantly lower reading, and spelling skills ( fourth and third grade levels,

respectively) (Streissguth et al, 1 991 ). 0 t h longterm studies have illustrated

the persistence of lower intelligence in affected adults (Spohr et al, 1993).

20

One af the paramount features of FAS is microcephaly. According to

Clarren (1 981 ), microcephaly may be the fint sign of CNS dysfundion.

Autopsies of FAS patients Micate that the brains of these inâividuals exhibit

similar malformatims caused by failure or intmpüon af the newonal and glial

cell migration, with some of the consistent anomalies Muding cerebellar

hypoplasia, and œrebml dysgenesis with hetemtopic œll clusters (Jones and

Smith, 1 973; Clarren, 1 981 ) Recently, magnetic resanance imaging (MRI)

studies have identified redudion of size of the basal gang lia, reduœd

diencephalon and absence or redudion in size of the corpus callosurn in

children expsed to alcohol in utero as cmpared with both m a l and other

mentally retarded control subjeds (Mattson et al, 1994). Mattson et al (1 994)

suggest aiet these reductions may be directly related to the cognitive and

behavioural diffiwlties associated with FAS. For instance, decreased basal

ganglia could be responsible fa such features as spatial memory deficits, and

lack of understanding conceming the consequences of their actions, Mi le a

hypoplastic corpus callosurn could be responsible for ADHD. and the problems

with the cornplex integrations between different brain systems.

Alcohol exposure in utero has been associatecl with many abnomalities

in the developing fetus varying in type, number, and severity with the most

severe affliction k ing F AS. The question renÿrins how alcohd inflids this

damage on the fetus. Although not yet killy elucidated, the mechanisms of

almhol teratogenicity in the develaping feus are slowly being teased out.

In teratology, a fw fundamental concepts an, hallmarks to the eff8Cf a

teratogen will have on the fetus. These fundamentals indude: dose, timing and

sensitivity. Ethanol, g iven its molecular weight, ionic nature and waterllipid

solubility, is a moleaile that can m l y cross the placenta and thus interfie with

proper embryonic development (Persaud, 1990). It is heavy matemal alcohol

consumption dwing pregnancy that is as-ated with the ocaimince of FAS.

However, it has been estimated that FAS is only seen in 3 5 4 % of affspfing

exposeci in utero to high alcohd levels (Jones et al, 1974). Why does it not

affect the other 60%? The answers to this question are varied. First, some

reports cite that it is blood alcohol content rather than the total amount of alcohol

wnsumed that predicts the congenital malformations asociated with FAS

(Persaud, 1990; Zajac and Abel, 1992). Recent research has detemined that

certain genotypes influence the rate of alcohol andlM acetaldehyde (an alcohol

metabolite) metabolian m i n a gken individual. Thus, the same dose of

alcohol can have varying efF8cts on different women and fetuses with respect to

blood alcohol levels and length of Ume peak blood alcohol levels are maintained

(Zajac and Abel, 1992).

Second, timing of exposure is also critical in detemiining the type and

severity of aie a m l i e s (Moore and Persaud, 1993). Most dudies on the

effed of alcohol on aitical developmental periods have been perfonned on

animal models, SPeQfically rats and miœ due to mir short gestation, large

litters and the quivalence between tfimesters of humans and rats (Zajac and

Abel, 1992). One organ systm which is partiwlarly nilnerable to the

teratogenic 8nds of alcohol is the central nervous system, due to its long

critical period in humans extending from the aiird week of gestation to the end of

the third trimester (see Figure 2) (Zajac and Abel, 1992; Moore and Persaud,

1 993). According to Zajac and Abel (1 992), alcohol exposure early in rodent

development (equivalent to the first trimester in humans) leads to neural tube

defects and modified neuronal pmliferaüon. Matemal alcaiol consumption

during the second trimester has been associated with decreased, and

disorganized neural tissue. This is due to alcohol's ability to interfere with neural

differentiation and migration of both the glial (neural support cells) and neuronal

cells (impulse conduding cells). such that patches of white matter are found in

the cerebral cortex and vice versa. Alcohol exposue during the second

trimester has also been assodated with the delay of certain developmental

landmarks leading to mivocephaly in the fetw (Zajac and Abel, 1992). Both of

these features have been documenfed by Jones and Smith (1 973) in FAS

autopsy cases. In the third trimester, the developing brain undergoes a growth

spuR Alcohol exposure is more detrimental at Mis time than at previous times

due to the imaS8d sensitivity of speciflc amas d the kain. Accordhg to Zajac

and Abel (1992) alcohol expure during the third trimester inteffwes with glial,

clendritic and synaptic prolifemtion, thus proper neural canducting pathways are

adversely aff8ded.

It has been suggested that alcohol may induce gmwth deficiency in the

fetus by depletion of nutritional requirements for normal grawth (Michaelis and

Michaelis, 1994). Ethanol has been implicated in directly inhibiting the

transportation of glucose and amino acids amss the placenta to the fetus. This

robs the fetal tissues of the energy and materials required for œll division,

growth and differentiation, thus contributing to the smaller stature associatecl

with prenatal alcohol exposure (Michaelis and Michaelis, 1994). Ethanol can

also a d as a vasoconstridor. By increasing the umbilical artery resistance, 1

decreases the amount of oxygen that the fetus is receiving, and thus c m also

interfere mth proper cell prolifmtion Ieading to intrauterine growth retardation

(Penaud, 1 990; Michaelis and Michaelis, 1 994).

How alcohd induces the development of the unique facial features

associated with FAS is still not completely understood. As many of the ear

anomalies and other manidacial anomalies associatecl with FAS are due to

embryonic malformations of the first and second branchial arches, it is possible

that alcohol exposure during this critical period may induce such dysmorphic

features (Church and Gerkin, 1988). Others suggest that the some of the

Figure 2. Diagrammatic representation of the critical periods in human development The first shaded portion of the bar graphs represent highly sensitive periods during which major anomalies may inwr, while the latter portion represents stages less susceptible to teratogens, during which minor anomalies may result- (Modifed from: Moore and Perseud, 1993)

observed features may ocair seamdary to restrided brainl head growth (Autti-

Ramo et al, 1992). Other hypotheses suggest that the fetus wwld have to be

exposed to a certain threshold bbod alcohol level during the first trimester, or

that pre-pregnancy alcohol consumption by the maher would be required to

cause aaniofacil dysmorphology (Lanoque, 1992; Zajac and Abel, 1992).

Abel and Hamigan (1995) have developed a mode1 which brings much of

the research foaissing on the teratogenic M8Cfs of alcohol on the developing

fetus, as well as results of studies on matemal risk fadors, to explain why

alcohol does not act as an "equal oppoftunity" birVi defect They propose that

there are certain "pemissive factors" or sociobehavioural risk factors such as

culture and soci08conomic status (SES) mat the mother posseoses, which

interad with certain biological fadors, or 'provocative factors", such as blood

alcohol levels, or presence or lack of certain enzymes, which create an intemal

environment, which exacerbates the M e d s of alcohol on the fetus. niey

hypothesize that the permissive and provocative factors act toge01er to inuease

the action of matemalIfetal hypoxia, and ftee radical formation, which are

thought to be two of the biological mechanisms by which alcohol tefatogenesis

works (Abel and Hannigan, 1995).

1.6 FAS EpidemiQLoOy

Abel and Sokol(1987) estimated the world wide incidence af FAS to be

1.9 per 1 000 live births. This estimate was based on a survey of the literature

on prospective and retrospective stdies of FAS. They acknowiedged that this

estimate might be conservative due to difficulaes in ascertainment, such as

diffiailties with FAS diagnosis, and increased infant martaiity. They also noted

that the incidence rates were variable based on the study sites, with the highest

incidence being reported in mothers who wiere black or lndian and those who

had a low SES. In these populations, the estimated incidence of FAS was 2.6

per 1000 livebirths as compared to 0.6 per 1000 livebirths in sites where

mothers were predominantly white and of rniddle SES (Abel and Sokol, 1987).

In 1991, Abel and Sokol revised their previous estimate of the world wide

incidenœ of FAS, whidi was based on prospedively gathered data. This

revised estimate attempted to weed out the 'Yalse positives" that they believed

were included in their previous estimate by exduding "less controlled"

retrospective studies. In the revised study, Abel and Sokol (1991 ) attempted ta

control for the over-representation of certain racial groups who may be at higher

risk than others of having a child wiîh FAS. by basing their overall projections on

the proportion of each of aie ethnic subpopulations within the total population.

This was canied out so that the higher risk grwps w l d not inflate the overall

incidence estimate. Acrording to this new methodology, Abel and Sokol(1991)

identiied the incidence of FAS in the western world as being 0.33 per 1000

births, with a demographic breakdown of the incidenœ estimate being 0.29 per

1000 livebirths in whites versus 0.48 pef 1 OOO Iivebirths in blado. A third report

of the world wide incidenœ of FAS was detennined by Able in 1995, due to the

inueased availabilïty of proopective studies regarding FAS since the fast report-

The world wide incidenœ of FAS was now calailated at 0.97 per iûûû livebirths.

Abel noted great variability a FAS prevalence both between counûies and within

countries. For example he states that FAS was twenty times more prevalent in

the United States vems other European countries (1 -95 versus 0.08 per 1OOO ),

and that within the United States the observance of FAS was ten times higher in

women who were black and of lm SES compared with their Caucasian, rniddle

to upper class counterparts (2.29 versus 0.26 per 1000) (Abel, 1995). However

in both the 1991 and 1995 revised estimates, the authors acknowledge that

Native Americans were not induded in the study due to a lad< of prospectively

gatheted data for that population. This ascertainment bias probably leads to an

underestimate of the world wide incidenœ given that other studies have reported

the highest incideme and prevalence rates in the Aboriginal comrnunities

(Sandor et al, 1 981 ; May et al, 1983; Robinson et al, 1987; Burd and Moffatt,

1994). In fect Chavez et al (1988) found that FAS rates were seven times higher

in African Americans, and thirty times higher in Native Americans, Vian their

Caucasian axinterparts (Chavez et al, 1988). May et al (1 983) have al- shown

that rates can Vary greatly within a given race. For example, the Plains tribes in

the South Western United States showed FAS prevalence rates approximately

10 times higher than the Navajo and Pueblo tribes found in the same region

(19.5 per 1000. verses 2.5 and 2.7 per Io00 respeaively).

Detennining accurate estimates of the prevalence and incidence of FA€

(partial FAS) or ARBD in a population proves even mon, challenging than that

for FAS. The proMem is that, unlike FAS, FAUARBD does not have dearly

defined, widely sccepted aiteria on which to base a diagnosis. Consequently,

some children be labelled if the physicien is mare that they were exposed to

alcohol during the pregnancy, while others be diagnoseci as FAE when there

are associatecl anomalies or oaier "FAS" characteristics deteded in exposed

diildren who do not meet the full aiteria for FAS. That is why it is hoped that the

diagnositic criteria outlined by the InsüMe of Medicine will be univetsally

applied, and aie new category "partial FAS' will replace the oM catch phrase of

FA€. It is expected that FAEIARBD is much more frequent than FAS, w-th

estimates being 3 to 5 times more fiequent than FAS (Schorîing, 1993).

As was previously stated, epidemiological data on the prevalenœ and

incidence of FAS is lirnited, but even more scarce is good data on the

prevalenœ and incidence rates for Aboriginal peoples. However, most of the

available data suggest that Amencan Indians and Canadian Aboriginals are at

high ri* for FAS (Aase, 1 981 ; May et al, 1 983; Robinson et al, 1 987; Duimstra

et al, 1993). In fact in the hallmark article of Jones et al (1 973) originally

describing FAS, six of the eleven patients identified wïth FAS were of Native

Arnerican Mgin.

The highest reporteci prevalenœ rate of ÇAS is by Robinson et al (1987)

in a Native Indian community in British Columbia. In thk study, al1 Native

children in the community (between the ages of 1 and 18) urne eligible to

participate. Criteria for FAS diagnosis were based on the reawnmended criteria

of the Fetal Aîcohol Study Grwp of the Research S0c1~et.y on Alcohalism (Rosett,

1980) and diagnosis of FAS was made independent of knowledge of matemal

alcohol consumption during the pmgnancy. This study identified 22 affeded

children ( F A S M ) out of 116 studied, with a sex distribution in the affaded

children k i n g 13 male verses 9 female. Two thirds of the children identified as

FASIFAE were mentally retarâed, one of the hallmark characteristics of in utero

exposure to alcohol. The prevalence in this community was calwlated as 190

FAS children per 1 OOO births. Robinson et al (1 987) acknowledged that under-

diagnosis of FAS axild have ocairred due to the anairopomorphic

characteristics of the Native diildren wtiich made measurements of certain

landmaks (su& as palpehl fisswe size) dtffiwlt, and thus limited the

camparability of these measurements to standards which are typically based on

the 'Mite" population measuremmts (Robinson et al, 1987; Abel and Sokol,

1991).

A second published report on the prevalenœ of FAS has been conduded

by Sandor et al (1 981 ) in British Columbia. Out of a sample of 76 FAS affeded

children, 69 of the 76 were af Native origin, and the remaining 7 were

Caucasian. In this report the au- state that there was a 10.9 to 1 ratio of

FAS affectai children in Native children versus Caucasians in the study (Sandor

et al, 1981). Hawever, 1 is possible that the number cited in this study may be

an overestimate due to an ascertainment bias that exists within aie methodology

of the study (Bray and Anderson, 1989). Al176 FAS patients included in the

study were found in two Vancouver hospitals, where it is possible that there

migM be an overiepresentation of M8ded native drildren who had been

referred to these tettiary care units.

An unpublished report by Asante et al (1985) detennined the prevalence

of FAS in 36 communities in the Yukon and Northwest British Columbia. The

basis of ascertainment of the 586 subjeds between the ages of birth to 16 years

of age, was via referrals by community agencies who had identifieci the children

as k ing handicappd. This method of ascertainment could lead to a bias in the

estimate of prevalenœ in the study, leading to the reporting of infiated

prevalence figures among these Native populations (Bray and Anderson, 1 989;

Burd and Moffatt, 1994). The reported estimates of FASIFAE prevalence in

these populations were: 46 affected per 1000 Native children in aie Yukon, and

25 affected per 1Oûû Native children in NoraiWest British Cdumbia, as

cornparecl to the prevalence rate of 0.4 affected per 1ûûû non-Native diildren in

both regions (Asante et al, 1985).

One notable study of the prevalenœ of FAS in American Indians of the

Southwest was camed out by May et al in 1983. The basis of ascertainment for

this study was via refwals, and those screened were fim three distinctly

different Native populations, the Navajo, Pueblo and Plains culture tribes. This

study not only identrfied FASI FA€ as a problem of the Amencan lndians but

also exemplified that there can be a great deal of variation be-n the different

tribes, probably based on the varying -al practiœs and traditions of eadi of

the cultures. The highest prevalenœ rate was noted for the SoUtttWest Plains

Culture, with the prevalenœ rate king 19.5 FASFAE children per 1000 births.

The Navajo and Pueblo cultures had considerably Jower prevalenœ rates at 2.5

per 1000 births and 2.7 per 1Oûû births respctively (May et al, 1983). Also of

interest was the frequent finding of mothers who had given birth to two or more

"alcohol-damaged" children, with 85 FASFAE affeded children being bom to 65

mothers. May et al (1 983) suggest that the differences in the prevalence

betwwn the thme Native wltures is not solely due to a higher proportion of

drinkers in the Plains culture tribe, but rather due to differences in the social

regulatïons of eacb of the cultures. The Plains tribes encourage individuality

and do not adively discourage behaviours such as risk-taking, drinking, and

defiance. Conversely, both the Navajo and PU8blo tribes emphasize conforrnity

to group noms, and thus exercise tighter control on alcohol-abusing behaviours,

potentially explaining why lower prevalence mes are repated for these Wbes.

Based on the data presented in the previws section, it would appsar that

Aboriginal mothers have a substantially increased risk of having children who

are aff8Cfed with FAS. The question then remains, is this increase in incidence

and prevalence rates due to a -tic suscep0t)ility in Native peoples, or could

the reported increases actually have nothing to do with FAS itself, but be

arMads of various meÜKIC)OIogical bisses in the vanais M i e s ? Atthough one

cannot nile out an increased genetic susceptibilky in AborÏginals until there is

condusive data to suggest it, in many of oie studies th8t have been examineci it

is expeded Wet methodological biases account for much of the obaerved

increase in rates in this ethnic gmup. Table 2 provides a summary af sorne of

the availabfe literatuie ~omeming the rates of FAS and partial FAS .

In designing a study to examine aie prevalence of FAS in a community, it

is important that the individuals axiducting the dysmorphology examinations be

persars who are traineâ at diagnosing FASFAE and who use the widely

accepted minimal criteria for FAS diagnosis. As has been previously stated,

FAS cm be a difFiailt diagnosis to make and thus, if one daes not have

experience in diagnosing such cases, many cases could be missed leading to an

underestimateof the actual incïdenœ/prevale of FAS in a community.

Conversely, an overestimate of the prevalenœ of FAS could be made l a large

number of ethnic minorities are induded in aie study. This inaease rnay not be

due to an adual increase in the number of 8n8Cfed individuals, but rather due to

similar physical charaderistics of the populations to that of FAS patients. For

example, m e features which are normal for one ethnic group (such as the

naturally occum'ng epicanthal folds and short palpebral fissures in Native

Americans) may be considered anomalous when compared to the prevailing

Tabk 2. Summary of some of the availaMe data on the Prevalence and Incidence fates of FAS and Pahial FAS.

Wong (1983) unpuMished

' denotes ARBD (FAS and Parbial FAS), 'denotes NonNative After: lnstitute of Medicine (1 996)

white standard, thus leading to a greater likelihwâ of FAS diagnosis in

individuals of that parüwlar ethnic g m p (Abel and Sokol, 1991).

Also of importance in the dysmorphology examination is for the examiner

to be blind to information of matemal alcohol use, emally in Aboriginal

populations where them akeady exists a stereutypic belief conceming

inaeased levels of alcoholism. Thus, by blinding the diagnostician to knowledge

of alcohol exposure the bias is minimizeâ. This methodology was used in the

study by Robinson et al (1967), but was not employed in moet of the other

studies.

A third important consideration in the dysmorphology assessrnent is the

age gmup oiat b being studied. It has been stated that the ideal period of time

for FAS diagnosis is behneen infancy and puberty. It has been reported that it is

more difficult to diagnose infants with FAS, due to the fact that the hallmark

charaderistics of FAS are less discemible at this period of time. This wuld

potentially lead to a decteased estimate of prevalenœ rates being reported.

Diagnosis past puberty also presents problems as the identirying charaderistics

such as gr- deficiemy, and hypoplastic maxillary area beaime less distinct

in the FAS adolescent and adult, although cognitive and behavioural problems

do persist (Streissguth et al, 1 991 ).

Another source of potential bias in the epidemiological studies of FAS is

the method of ascertainment of the subjects. In order to obtain accurate

prevalence rates in a specifed region, it mnild be necessary to study evecy

family and chiM, which is timecwwuming, costly and impradical (Robinson et al,

1 987). hr general. community suveys, where al1 children in the community are

assessed, will provide a more refiable estimate of prevalence than those studies

which ascertain their subjects through variaus referral meüiods. Relying on

rderrals as the ascertainment criterion, incmases oie chance of bias in the

individuals seen. By this, we r&r to the fad that there will be a higher

proportion of affectecl individuals being seeri in the study, and thus lead to an

increase in the prevalence rates for that shidy.

Care must be taken when designing a community ascertainment study.

First, given that FAS has been associateci with increased morbidity and mortality

(Burd and W a t t , 1994). a substantial number of cases could be missed in the

community, due to the fad that some affectecl perrons are no longer living. In

order to compensate for this potential uider reporting of prevalence in the

community, al1 death records should be assessed to identify the true number of

afïeaed individuals in the community. Burd and W a t t (1 994) also point out

that, in some cases, community studies rnay also lead to a bias in the

prevalence of FAS within an ethnic gmup, partiailarly l a cammunity is surveyed

because FAS is thought to be a major health problem there- It is possible that

there may be a legitirnate i m s e in prevalence in the defined geographic area,

but caution should be used when generalizing f m the partidar area surveyed

to the entire ethnic group.

A final, but important source of bias in the estimate of prevalenœ rates, is

the failure to separate confounding variables, which may produœ characteristic

features similar to those oeen in FAS. For example, Bray and Anderson (1989)

criticized the Robinson et al (1987) study on the basis that they did nat separate

' out confounding variables, such as cigarette use in rnothers, Mich could also

account fw the obsewed growüi retardatim, or matemal use of other teratogenic

dnigs mich could cause similar âysmorphology and CNS dyshindion. Failure

to adjust for such confounders can lead to over-8stimates of the prevalence of

FAS in the specified population.

Comrmnihr.

The general study from which this thesis stems was a collaborative effort

on the part of the researchers and the band cwncil. The researchers had

reœived a grant from the Canadian Pediatric Society Cornmittee on Indian and

Inuit Health to develop a simple suwey midi could be eventuall y self-

administemci by the mmunities themeIves to identify individuals with FAS, or

other ARBD. This survey was to ôe condudecl at minimal costs, and require

minimal specialist input. At the same time, the community concemed had

contaded one of the researchers, sfating Mat the school was having an

inueased number of behavioural problms, which they thought could be

attributabie to alcohol expure. Thus the team of investigators set forth to

develop such a survey, with a number of ob~ectives in mind. The primary

objectives of the overall study were :

(1) to develop a simple sunrey which caild be administered with

minimal cast and minimal specialist input;

(2) to cletmine the prevalence of FAS and partial FAS in one

Manitoba First Nations Community;

(3) to provide diagnostic and rehabilitative services to FASlparüal

FAS children in the community who had not previously b e n

diagnosed;

(4) to assist the community with the development of preventive and

rehabilitative pmgrams for FASlpartial FAS.

Secondary objectives for the overall study included:

(5) examination of the relative contribution of alcohol during

pregnancy compared with other sodoâernographic variables to

dificulties in sdiool performance and behaviour.

(6) to develop noms for craniOfwal rnoiphometric analysis in a group

of Aboriginal children of school age.

(7) to detemine whether facial dysmorphology in Abonginal children can

be reliably detemined from a photograph.

(8) to determine if parental report of school achievement on the

Achenbadi Child Behavian Cheddist is as reliable as teacher report on

the same test and a more cornplex educational test battery (Woodcock-

Johnson).

(9) to determine the correlation between educational, social and

behavioural findings with morphomebic analysis.

This research proposal was appmved by the University of Manitoba Fawlty

Cornmittee on the use of Human Subjeds in Researdi in July 1995.

This study is important not only from a developrnental point of view, but

also fiom an epidemiological standpoint To date, very few epidemiological

studies with regards to the rates of FAS, partial FAS, or Alcohohelated affects

(ARBD and ARND), have bwn condudeci in Canada. The M i e s that do exist

have been conducted in Nadinwestern B.C. (Robinson et al, 1987; Assante et al,

1985; Wong, 1 983), apart fmm one incidence study conduded in Saskatchewan

(Habbick et al, 1996). No study to date has attempted to examine the

magnitude of mis proMem within aie Manitoban population in general, or in

specific referenœ to the First Nation Communities within the province.

1.9 F- ofthe-

Data used for analysis in this thesis was coll8Cfed as part of the larger

Community FAS study. The aieais is intended to examine in detail the

epidemiology and âysmorphology assessment aspects of the larger study.

Prevalenœ rates m'Il be calwlated for this community and compared to

previously reported literature rates within Canada. It is expected that this

community is not unique with respect to its drinking habits, and thus it is

expeàed that the prevalence rates will fall min the previously reportecl ranges.

Examination of d y ~ m o ~ h o l ~ g y parameters, such as the maniafacial and

other morphametnc analyses, w*ll be conduded to determine if the physical

characteristics used to identify FAS or partial FAS in Caucasian populations, can

be applied to Abonginal pqulaüons. which are known to Vary from the

Caucasian population with respect to features such as the natural presenœ of

epicanthal folds. It is hypothesized that, in general, the cardinal features such

as growth retardation, tekanthus, and shoiterted palpebral fissures will be

important physical chamcterisW in identifying those afF8ded preMtally by

alcohol.

Thirdly, the thesis will conduct an in depth analysis af the morphometnc

data collected on the "Normal", segment of aie study population and ~ A l l attempt

to construct normal standard gr- curves for al1 morphometric parameters

collected, based on these data. It is expected mat the Native school-aged

population may differ *th respect to sire and maniofadal features, and that

cornparison of these children against nomial standard cunres which are primarïly

mstnided based on morphometnc data colledeci in Caucasian populations,

may lead to enwieous (either infiated or deflated) estimates of the true

prevalence of FAS and partial FAS in the cornmunity. In order to test such a

hypothesis, perœntile ranks for each of the morphometric data of the FAS and

partial FAS individuals will be compared when plotted against the previously

established Caucasian standards and the newly generated Native ones to

detemine if an increase in anomalies can be detected,

2uHmQd4

L-

The Manitoba First Nation Community in which this study was anduded

wishes to remain amymous to avoid stigmaüzation that may result from the

publication of the sensitive findings of this study. It can be said, however, that

the community studied is a rural comrnunity which identifies itself as having had

problems with alcalot. Further information concerning aie characterization of

the community tests with the author.

I n f o m Consent Colleçtim

A list of al1 children bom within the ten year study period which spanned

1981 to 1990 was obtained frwn Medical Services Branch (MSB), as well as a

death list of those bom within the cohort. According to MSB, 352 children were

listed on the band list as being bom maiin the spcified cohoR H was not

expected that al1 352 children would be on reserve, as some may have been

placed with CFS, been living Off-resefv8, attending Scnool in other neighbouring

towns, or have died. Examination of the cohort's death list indicated that 1 O

children in the whort had died as of late 1995, none of whorn had any evidence

of alcohol related biM def8ds. Secondly, a Iist of al1 children enrolled in the

1995 - 1996 sdioal year was obtained from the local school. The student

enrolment for the local school was 254, however, only 243 of the students fell

within the birth cohort and thus were eligible for study- Another exclusion

critmbn was that the child had to attend the local school. This excluded ctiildren

who did not attend the school regularly, and thcse who attended school df-

reserve. This provided the base fiom which ouf study population was

ascertained.

Researchers, in accordance with the band cauna'l's directives, hired and

trained two local aboriginal worlcem to aid in the coordination of this study. The

local coordinator was responsible for obtaining infonned consent from parents,

Legal Guardians or Child and Family Swiœs (CF S) (depending on the status of

the child), for the participation of their child in this local study. The job of the

local coordinator was four-fold. Rie fimt responsibility was to visit the homes of

children eligible for study participation based on the school Iist, and explain the

study to the parents. if the parents agmed to allaw their child to participate in

the Community FAS study, then the coordinator read and explained to the

parents the thme consent f m s to be signed (Appendix A), and witnessed the

signing of the foms. The first fonn was a g e m l consent, midi explained the

purpose of each aspect of the stuây, and the approximate length of time the

child would be required to spend with the researchers. This fom also stressed

the voluntary nature of the study and that the child or parents could withdraw at

anytime during the study without penalty to the chiM. Anonymity of photographs

and child's records urne also stressed. The second consent fom obtained

permission fmm the parents, to release pertinent information to the school, so

that appropriate measures cwld be set up to help aie child leam according to

his or her own sWal needs. The third consent fonn obtaind parental consent

to examine the chiWs birth mords to o b i n i~omiation such as growth

parameters (height, weight, and head circumferenœ), Apgar saxes, and to

check the Manitoba Nursing Oatabase sheet to confinn whether alcohol was

used during pregnancy.

The second part of the local coordinators' responsibilities included

conduding a Matemal Interview (appendix 6) wÏth the mother (if more than one

aiild was being registemd in the study, a Matemal lntenriew for each diild was

completed), and administering the Parent fomr of the Achenbadi Child

Behaviwr Checklist (CBCL) (Achenbadi, 1978; 1979; 1979b). The Teadier

form of the Achenbadi CBCL was completed by the local teadiers at the end of

the 1995 school year for all children attemling the local school.

The Matemal Interview itsetf consisted of questions regarding the status

of the child (natural, adopted, or foster). If the child was a foster child or

adopted, the parent was then asked whether alcahol was one of the reasons for

placement. Other questions included information regarding the nurnber of

people living in the house, source of income for the household, and the

eduwtion level and occupations of aie mother and head of the househdd. if the

child was a foster child or adopted, the intenriw wwld stop at this point, unless

the adoptive3Rbster parent was a dose relative to the mother, who might be able

to answer sorne of the other questions relating to pregnancy and family histories.

In mer cases. where the diild was eioier in a foster hane, or had been

adopted, and the natural mother was still on reserve, attempts were made to

contact the natural mother to complete the questionnaire.

The remainder of the interview conœmed itself with alcohol use, or other

drug use during pregnancy, questions regarding the birth of the diild and

postnatal life, numbers of children and stillbirthsl miscarriages had since the

bitth of this child, questions regarding mental retardation or birth def8ds in the

family, both immediate and extendeci, and questions with regards to

msanguinity of the parents.

The Matemal Interview provided the researchers with one retrospective,

seIf-report source of information reglcohol exposure during the pregnancy. In

the Matemat interview, a version of the TWW< (Russell, 1994) was used to

identw high risk drinknrg during the pregnancy. The mothem were asked to

recall the time that they were pregnant with the child in question, and answer the

questions induded in Table 3. The TWW< test is a combination of other self-

reporting saeening tests such es a modified version of the Michigan Alcaholism

Saeening Test (MAST) representing questions two, four, and five (Selzer.

1971 ), TdCE (Sokol et al, 1989) representing question one, and the CAGE

(Ewing, 1984) tepresenting question three. The TWEAK is mred on a seven

point scale. Questions relating to using alcohol as an eye-opener (question

three), amnesia (question four),and aie Cut dawn question (question five) each

score one point if a positive response is obtained. Two points are given if the

woman answers five or more on the toleranœ question (question one), and the

same point value is scored if a positive mspons8 is obtained for the worry

question (number Mm). A score of two or greater is considered to be indicative

of "risk drinking. According to Russell (la), aie TWW< test has been found

to have sensitivity and specificity levels of 91 % and 77% respectively, in

cornpaison to the same masures for the T-ACE (89% and 79%), and both have

been shown ta be more effective for saeening than the MAST and CAGE

questionnaires.

Two other sources of alcohol exposure information were also examined

as part of this M y . if the chiM was an adapted or foster child, the adoptive /

foster mother was quesîioned at the start of the matemal interview as to

whether, to their knowledge. alcohol was one of the reasons for the child's

placement (Matemal lntewiew Question number three part three). An affirmative

answer to this question was assumed to also mean that the diild had probably

been exposed prenatally to alcohol. The third source of information conceming

alcohol use during pregnancy came fmm examination of the Nursing Database

sheets in the childs birth records. This asped of alcohd history colledion will

be disaissed further in the following section.

Table 3. The THlEAK Questionnaire.

Question Score #

2 W Have dose friends or reialbs Wonnd or 2 corn pl- about your drinking in the past yeae _ ,

3 E Eye-opeinr= Do you somelimes take a drink in the 1 moming wheii you first get up?

4 A kmi.rir: Has a fiiend or frimily meniber ever told 1 p u aboutthhgs you said or did whiie p u were

dhking that you couid not rememûer?

After, Russell (1 994).

Consent was obtained from each parent or legal guardian to examine the

child's hospital records at theif hospital of birth. The majoflty of the children

were bom in 7 provincial hospitals, 4 within the city of Winnipeg, and 3 outside

of the city. In the rare instance when a child was bom wtside of the province,

hospital records could not be exarnined.

The purpose of examining the diiWs birth records was two-fold. The

primary purpose was to obtain information regarding alcohol use during the

pregnancy. This information was to be obtained via review of the Nursing Data

base sheet, a questionnaire which was developed for use in 1980. This sheet

asks the moaier questions mgarding ather pregnancies, health during the

pregnancy, and indudes one 'les / no8' question with regards to alcohol use

during the PreQmncy. ît has been found th& there is a quite high reliability

respect ta the cornpletion of this question and questioning the mother with

regards to the same question. Thus it was anticipated that thb review would

provide researchers with a rnethod of confinning the matemally repomd alcohol

use during pregnancy, as in many cases the mother must remember far back in

time to the pregnancy. However, the use of such fonns by each hospital was

voluntary. Many of the city hospitals had used the foms to document alcohol

exposure, but the rural hospitals, where the majority of children were k m , did

not use this fomi at all, or use of aie f m by the institutions was irregular.

Nuning, Physician, and Social Worker notes with regards to the birth and

postnatal life of tha child in hospital were also reviewd to see if any

documentation existed regarding alcohol use duing the pregnancy. Few

hospital charts cuntained information regarding alcohol abuse duing the

pregnancy, and correlations between the hospital repom and the matemal recall

could not be determined.

Secondly, the charts were reviewed ta identify any problems during

pregnamy, or post natal life (sudi as jaundiœ),apgar scores, and growth

parameters at birth. A copy of the hospital review forrn is appended as Appendk

Ali drîldren on whm we had conseni were examined by a

dysmorphologist 1 geneticist and his assistant, both of whom at the time of

assessrnent and categorization of the children were blind to the alcohol

ecposure histories, school pe rnanœ, and behavioural status of al1 children.

The Dymrphology assessrnent consisted of three parts examining 46 different

parameters, and took approximately 1 O minutes per child.

The first aspect of the assesment involved taking two photographs of

each child, a ftontal (full face) photograph, and a lateral view d the child. The

children were asked to place theif haïr behind their ears, so that the ears were

visible, and asked not to srnile, so that their faces would be in a natural position,

to allow the researdiers to perform sorne morphometric analyses of certain

craniofacial landmarks on the pidures (Bookstein, 1986; Clarren et al 1987;

Astley et al, 1 992; Astley and Clarren, 1 995; 1 996). The phdographs were

taken at a standard distance of 24 cm, using a Polaroid Spectra camera, with a

close-up Fi 12 lens. The use of colour Polaroid grid film, where one grid blodc

equalled 1 cm, was used to aid in the measurements of the facial landmarks to

be studied. The photographs also m e d as a method to test intembsenrer

reliability for FAS diagnosis. This aspect of the study will not be elaborated on

in this thesis, as it is the foais of a separate analysis.

The second aspect of the assesment involved the measurnent of

growth parameters such as height, weight, and head cimmference, as well as

several craniofacial landmarks such as i n w and outer canthal lengths,

palpebral fissure lengths, and philtrum length (se8 Figure 3). These

measurements were made diredly on the child using a physicians' measurïng

tape which was graded in millimetres. Each of aie measurements was then

plotted on a standard graph f a each parameter (based on Caucasian noms), to

detemine the chilcrs percentile rank for each parameter. One of the facial

landrnark measurements, the outer canthal, nasal, outer canthal (ONO) angle

(Hall et al. 1989) was made using the frantal photograph of the child. This

measurement allowed for a quantitative measure of the midfaœ region of the

child. A fine was drawn from the outer canthus of each eye to the base of the

columella (midline), the resultant angle (ONO) was then measuredÇ'E" in Figure

3), recorded, and the diild's perœntile rank was determined via plotting the

ON0 angle value on a standard graph. A ratio of palpebral fissure lengthlinner

canthal distance was calculated based on the measurements obtained in the

quantitative assessrnent of aaniofacial feahires. This ratio has b e n shuwn to

be a differentiating feature between "normal" and FAS individuals (Astley and

Clarren, 1 995; 1 996).

Figure 3. Diagrammatic representaüon of craniofacial landmarks rneasured as part of the Dysmorphology Assessrnent section of the Community FAS study.

A: Outer Canthal Distanœ 8: Inner Canthal Distance C: Palpebral Fissure Length D: Philtnim Length E: ON0 Angle

Diagram madified from: Olsen and Tuntiseranee (1 995).

Th8 third aspect of the assessrnent invohred qualitative observation of

several other features of the children. Some of the features included: the slant

of the palpehl fissures, formatian of the philtrum (normal vs smooth) and

palate (normal, cleft, or high-arehed), appearance of the eyes, ears, and chin,

finger anomalies, contractures, hean anomalies and othen listed in Appendü D.

At the end of each assement the dysmorphologist was asked to

categorize the child in one of four categories based on the dysmorphology of the

diild alone. The four categories induded: "nomial", FAS, partial FAS, and

dysmorphic, where the fast category induded children who do not appear

normal, kit it is expected that the d ~ ~ c e s observed are due to familial

variants, or due to reasons other than alcohol exposure. Classification as FAS

and partial FAS were baseâ on the diagnostic criteria set forth by the lnstitute of

Medicine (1 996) (see Table 7 ).

A battery of psychoeducational tests were uülized to obtain information on

how the child was functioning on the cognitive and behavioural levels. These

tests were administered at aie schod by a retired teamer, who had received

training on how to administer each of the tests, and was blind to the alcohol

exposure status of Bach child. This part of the study generally spanned forty-five

minutes to one hour in length. Given that this thesis m'Il not f m s on the

educational aspect of this study, the following provides a bdef overview of the

instniments uülized by the researchers in the m a l study:

(1 ) Woodcodc Johnson Cognitive Battery (Woodcock and Johnson,

lm)

Two subtests of this battery were used: the Memory for Names test

which tests long terni reûieval in the children, and the Analysis-

Synthesis test, whidi test fluid reasoning skills in the children.

(2) Beery Test of Visual Motor lntegration (Beery, 1982)

This test was conduded in the standard way in which the diild is asked

to re-draw a pattern mat they are shawn, as well as a nonstandard

method, whereby the pattern was s h m to aie child, helshe was asked ta

wait five seconds and then re-drawn the fom from memory.

(3) Test of Visual Attention (T.O.V.A@)

This test involved using a self-scon'ng amiputer program to test the

visual attention levels of each child.

(4) Wechsler Intelligence Scales

m e digit-span subtest was used to test memory.

(5) Canadian Test of Basic Skills (CTBS) and Canadian Achievernent

Test Scores.

The school provided the researchers with the scores of the CTBS

(for aKwe in K - grade 2), and CAT (grade 38). 60th test academic

achievement

At the time d the Dysmorphdogy a ~ ~ ~ ~ ~ m e n f . aie dysmorphologist was

asked to examine oie childs growth parameters, morp-c percentiles, and

general appearanœ. and dassify the child i n t ~ one of the fou categories. This

diagnostic classification by aie dysmorphologist was based solely on

dysmorphology, as the dysmorphologist and his assistant were both blind to

alcohol erposure histories as well as the behavioural and psychoeducational

assessment results. After al1 data collection was completed, the research team

reviewed the research charts and data from those children with suspectecl FAS

or suspectecl partial FAS. This review included the Dysmorphology assessment

results, matemal intenriew results which inciuded a recall assessment on alcohol

exposure during the pregnancy, hospital chart review results, as well as the

results of the Adienbach child behaviwr died<list (both parent and teacher),

and psychoducational battery results. Based on the review of the cham, some

of the children were then redassifed, basd on diagnostic criteria used to

identify the FAS and partial FAS children. Children were considered FAS, if they

had been classifieci as such by the dysrorphologist. had a positive or

undetermined alcohol exposure, and usually had behavioural andlor educational

diffiwlties. Classification as to Partial FAS proved more diffiwk as there are not

as strict guidelines for its diagnosis. However, in this study, children were

classified as partial FAS if they had been classified as such by the

dysmorphoiogist, had a confirmed alcohoi exposure. and had behaviourai andior

eduaitional difficulties. Children who wero not exposeâ to alcohol prenatally but

were originally dassified as FAS or partial FAS based on dysmorphology alone

were entered in a separate caegory, "Dysrorphic 2". Mer the new diagnostic

categories were established, researchers then contacted the parents of these

alcohol aff8Cfed children via a letter, OffMg to meet and disaiss aie childs

findings with the parents. Counselling, referrals to appropriate agencies and

assistance in coping with the &i#s resufts wem Onwd to the parents dunng

this meeting. The meetings were in general a half hour in length.

Native normal curves were created through the mathematical

manipulation of the morphometric data collected in the "Normal" diagnostic

category, as per methods describecl in pieexisting literature (Lucas and Pryor,

1935; Laestadius et al, 1969; Feingold and Bossert, 1974; Jones et al, 1978;

Fuchs et al, 1980; Merlob et al, 1984) . The category was divided by sex and

each category was then divided into one year divisions frorn age five to ffteen.

Two-tailed student t-tests were perfonned on the male and female categories to

detemine if the results could be poded for the sexes, or whether separate

wwes must be aeated for each sex for each partiailar rnorphometnc parameter

measured in this study. For each age categogory, the number of individuals were

noted, as were the range of rneasued values. Means and standard deviations

were calwlated for each age goup. N m a l curres for the morphometric data

were constructed, by calculating and plottiftg the rnean for each age group, plus

and minus one and two standard deviations f i the mean. fhus, on the actual

genefated m e , the standard devimons and m a n mwld represert the second,

sixteenth, fflieth, eighty-fourth, and ninety-eighth percentiles respedively,

assuming that 68% of al1 observations lie within the boundary p 2 o, and

approximately 95.4% are bound by p 2 2 0 (Jekel et al, 1996). Previously

established nonnative wwes ueated based on Caucasian populations have

been added as a shaded area behind the Native nmative graphs, to allow for

cornparisons between the hnro graphs. Morphometric data from the FAS and

partial FAS categories were then plotted on the new Native normal wnres, to

allow for cornparison of aff8ded individuals against their own pers. Differences

between percentile ranks on the Caucasiai arves, and the native wrves were

noted.

Dysmorphology parameters were compared in the following analyses:

exposure versus no exposure to alcohol; amiparisons betwwn graded levels of

alcohol exposure; and comparisms between the diagnostic catmes using

univariate analysis. With respect to the graded levels of prenatal alcohol

exposure, three categories were cteated: no exposure, low exposure, and high

exposure. The high prenatal alcohol exposure category included those

individuals Who wem adopted or wen, in foster are, and for whom it was k n m

that alcohol was a prirnary reason for placement. This categofy al- indudeci

those ehildren whose moalrers had scored 2 2 on the T\NEAK test. Low

prenatal alcdrol exposure was defined as evidenœ of exposure, but failure to

meet the indusion aiteria of the high expowre group. Differences behwn

groups were wnsidered to be statistically signifiant at aie p s 0.01 level, and

considerd to be af barderlin8 statisücal significanœ for the range 0.01 s p s

0.05. The statistical significanœ level of p 60.01 was chosen due to multiple

cornparisons which were made in the analyses.

In aeating the Native nomal m e s , statistically difrent means between

the males and females were deteaed using a hno tailed Student t-test at the p s

0.01 level. If this level was noted between the means of the two groups

("normal" males versus 'homal" females) on a given parameter (such as heigM,

weight, etc) then graphs were created for each sex. if the diflrnnce betwwn

the means was not cocisidered statistically different, the data between the two

sexes were pooled to create the cuwes.

Cornparison of the median lines on the normal Naive curves, to those

extrapolated from the nomal Caucasian counierparts were tested for statistically

significant differenœs using a paired Student t-test, with statistical significanœ

being measured at the p s 0.01 level. Statistical tests weie perfonned using the

SAS (Statisücal Analysis System) package (Release 6-08, 1 989; SAS

Institute, lnc. ).

58

Out of 243 possible candidates for participation in the study, 207

consents wsre collecteci, with only 7 refusals to participate in the study

doaimented by the local coordinators (3% rehrsal rate). Twentynine individuals

were not cOnfacfed by aie coordinator for reasons uiknawn. In accordance with

the exdusion criteria, another 29 individuals for whom consent was cdleded,

w r e not eligible for analysis due to birth dates falling wtside of the specified

cohort, absenteeism from SCIIool on assessrnent dates, or due to moving off-

reserve prior to assessment. Thus the final sample sire for this study was 178

individuals, whidi corresponds to a 73% ascertainment rate.

. idemiologv R e s a

3.1.1 Aîtohd Exporum

As can be seen in Table 4,46% of the study sample had been exposed to

alwhol in utero. This number can be stratifieâ by graded level of expsure, in

which case 30% af aie sample had ben exposd to high levels of alcohol, while

the remaining 16% were wnsidered low exposures.

Analysis of the number of children prenatally exposed to alcohol per year

of the cohort indicate that the exposure rates observed in th8 early venus the

later 1980s were 44% (32/73) and 42% (441105) respedively (Table 5).

table 4 m Akûhol Exposure Data.

Number of children Exposed Exposure Rate ( N= 165)

Total number of children expased to Alcohol 76 46% pmnatally

Total number 49 30% (high exposum)

TaMe 5. Break down of the Bitth cohort, illustrating exposure levels per year of birth, and numbers of FAS / Partial FAS cases pet year of birth.

Year of Birth Number bom P r P a r

Number with positive alcahol exposures per par born

Exposure Percentages per p a r of birth

Number with ARBD per year of birth (FAS+partial FAS)

2

3

3.1.2 Diagnostic Classification cabgovies

Table 6 sumrrtarizes the number of children per diagnostic classification

category. Prior to complet8 chart review, the Dysmorphologist, blind to alcohol

exposure, was asked to categwue each child into one of the four categories

listed, based on dysrnorphdogy alone (Dx). At the end of the data collection

phase of the study, full charts were revieuued for each child, and blinding to

alcohol exposure was now abandoned. At this point in time, based on

behavioural, educational, alcohol exposure information, and the âysmorpho~ogy

assessment, a new diagnosis was given to each child based on al1 results

obtained in the study (NDx). In the case of the FAS diildren, two were removed

fiom the FAS gmup ta the Dysmrphic 2 group based on no evidence of prenatal

al cohol exposure. lndividuals were included in the new category-Dysmorphic 2

if they had been excluded frorn the FAS and Partial FAS categories due to la&

of alcohol exposure, but did not appear phenotypically "normal". It is thought

that children in this category have abnormalities which are due to a normal

familial variation or causes other #an prenatal alcohd exposure. Even though

the exposure numbers illustrate that only 9 were exposed, the NDx column

indicates that 11 children were assesseâ as being FAS. This is due to the fact

that exposure data was not available for the remaining hm children, yet they met

al1 other diagnostic aitm-a for indusion in this category as expressed by the new

diagnostic classification guidelines of the lnstitute of Medicine (1 998). Similarly

on1 y 8/13 previousl y classifieci partial FAS children had positive alcohol

exposures. Five d i i ldm were thus redassified as Dysmorphic 2 based on the

fact that aiey did not appear "normal" phenotypically, but their abnomalities

wuld not be accounted for by prenatal alcohol expure. One other child was

removed from this gmup and added to the Dysmorphic 2 classification even

though she had been expsed prenatally to alcohol. On initial observation the

dysmorphologist thought she may have some but, not many of the features

associated with FAS, such as telecanthus. However, the majority of the

morphometric data did rot f t this initial impression, as well, she was fundionhg

nonnally in school, and was not assesseci by teachers or parents as having

behavioural problems. Thus, upon MI chart review it was decided that she did

not exhibit enough charaderistic for adequate indusion in the partial FAS

category, despite her positive history of alcohol expure. Wth respect to the

Dysmorphic dassification, 911 9 wwe exposed to alcohol in utero.

Finally, Soi133 (38%) of the "Nomal" classification group had evidenœ of

positive alcohol exposure in utero. This gaip provides a unique gmup to study

as 1 allows one to look at the potential leaming and behavioural eff-s of

alcohol exposure on the child who does not manifest physical charaderistics of

such exposure. That is, the alcohol may afkct the child behaviourally and

cognitively, wiatout observance of the classic FAS phenotype. It wwld be

important for the school to identify these children, sinœ, like their partial FAS

counterparts, they may be the ones who do not receive additional resource

ducational help.

Examination of the perœntage of FAS and partial FAS children barn per

year of the study p8fïod (Table 5 and Figure 4) also reaffinns the alcohol

exposure data, in that a significant deaease is nOt o b ~ e ~ e d between the early

and late 1980s [Il % (W3) versus 9.5% (1 01.1 Os)]. The y e n of highest alcohol

expasure rates, also correspond diredly with üie years in which the highest

nurnbers d FAS and pacüal FAS children wefe bom. For exampie, in 1982, a

67% exposure rate wes documenteci with airee FASI partial FAS children bom,

mile in 1987, a 62% exposure rate was observed with the number of FASl

partial FAS children bom equalling four (Figure 4).

Based on the intonnation presented in Table 4 and Table 6, it is possible

to calailate the risk of FAS fmm pregnancies characterized by high levels of

alcohol exposure. Based on these calculations it appears that 16.3% (8149) of

the high exposures resulted in FAS. This figure increases to 30.6% (1 5/49) if we

include high exposure rates for FAS and Partial FAS combined. These numben

are based on a sample sire of 165, as thirteen exposures were unknown.

Table 6. Breakdomi of study sample by diagnostic classification categories based on the dysmorphology assessment ody (Dx) and based on full &art review (NDx).

FAS 1 13

8 (2 reclâssified fram

FAS category, 6 reclassitied from

Partial FAS category)

133

Y

Partial FAS 13

Figure 4. Graphic representation of the number of births pet year of the whort, number of exposures to alcahol per year and number of children bom with FAS or Partial FAS per year of the cohort.

3.1.3 Pmvalence

Prevalence rates of FAS and Partial FAS can be calculateci for this

partiwlar community, based on the previous data. Ail calwlations m'Il be based

on the new diagnostic cabgories, after full diart review (NDx), as this category

takes into account al1 relevant data required in making an FAS diagnosis:

dysmorphology, exposure histories, behavioural, and psychoeducational testing .

A range of prevalenœ rates can be detemined based on which

population size is used as the denominator of the calculation (Table 7 and

Figure 5). A minimum prevalenœ rate is derived using the MSB cohort size of

352 children. Intermediate figures repressnt prevalence calculations using the

school list population, of 243 childm bon M i n the speciried cohort. In

calculating both the minimum and intemrediate figure, it is assumed that only the

diildren enroled in the study are aKwe aneded wÏth FAS or partial FAS, and that

no other aff8Cfed children would be found in the proportions of the populations

not studied (49% and 27%, fespectively). The maximum figure is calailateci

based on the assumption that the study sample is a random sample of the

school-aged population in this mmunity and thus the âenominator for the

calculation is the study sample size of 178 children. As noted in Table 7 and

digrammatically depided in Figure 5, the range for FAS in this community is

between 31 - 62 cases per 1000 children, partial FAS ranges from 20 - 39 cases

per 1 OOO children, and the combined figure for all foms of alcohol related birVi

defeds ranges from 51 - 1 O1 cases per 1000 children.

Table 7. Range of Prevalenœ (per 1000 children) for FAS, Partial FAS, and Combined ARBD in this study community.

Figure 5. Graphic representation of the passible range of prevalence rates of FAS, partial FAS, and combined FAS and Partial FAS in the study Community (per 1000 children).

c Examination af me dysmorphology assessrnent results by any level of

prenatal exposure to alwhol (Table 8), illustrate that the only parameters that

appea to differ statistically between aie exposed group and the non-exposed

group inciude: height (p=O.O169), weight (p=0.0019) and head cirarmference

(p<0.0001) percentile values, as detamineci by use d the Caucasian nomal

standard graphs. The new diagnostic categories based on full chart review are

afso significantly different with respect to the exposecl and non-exposed groups

(p<0.0001). Accordingto Student t-test analysis, the erposed group was shorter

(mean percentile rank 58 exposed versus 68 non%xposed), weighed less (62

versus 76). and had smaller head circumferences (58 verws 77) than their

unexposed countetparts. Other dysrorphology parameters that did not meet

criteria of statistical significanœ at the p=0.01 level, but would be considered

borderline significant (0.05~p20.01) when examined with respect to alcohol

exposure include brachycfactyiy (p=0.059), diagnosis based on dysmorphology

alone (p = 0.02) and palpebral fissure length percentiles (p=0.037). With

respect to brachydactyly, th8 expased individuals showed a 4% rate of

brachydactyly versus no cases oôsewed in the wiexposed individuala

Palpebral fissure length perœntiles were l o m ~ for the exposeci group in

cornparison to the unexposed g m p (mean percentib rank 38 versus 47).

Data analyzed with respect to graded alcohol exposures (high, low, and

no alcohol exposure) using the Wilaixon signed rank sums test, indicate that the

71

same dysmorpholagy parameters significantly difbr statistically behween the

groupe (Table 9). These pammetem indude: height (p=û.W33), wigM

(p = 0.0001 ), and head cirarrnference percentiles (p = 0.0001 ), diagnosis based

on dysmorphology alwie (p=O.W3), as well as the new diagnosis based on

dysmorphology and mplete chart reviw (p<0.0001). According to the mean

percentile ranks, individuals mai high levels of alcahol exposure wbre shorter

(high = 52. low =68 and no exposure = 68), ligMer (high = 55, low =75, no

exposufe = 76), and had smaller head cirwmferences (high =52, lw = 69, no

exposurer 77). One dysmorphology parameter which was only wnsidered to be

of borddine statistical significame with respect to alcohol exposure, but which

reaches statistical significance when alahol exposure is graded, is the

palpebral fissure length percentiles (pt0.0017). Individuals who were exposed

to high levels of alcohol in utero exhibit the shortest palpebral fissure lengths

(mean percentile rank high = 32, lm = 49, no exposure = 47). Hcwever, it is

not the low exposure gmup who rank second with respect to short palpebral

fissures, bot rather the non-expsed group. As was o b m e d with the alcohol

exposure analysis, boai rnidfaœ and brachydadyly were considered to be of

borderline statistical significance (p = 0.023 and p = 0.041 respedively), when

analyzed with respect to greded alcohol exposure.

A description of the statistically signifiant results of the cornparison of

dysmorphology assessrnent parameters versus diagnostic categories based on

dysmorphology alone is provided in Table 10. The Wilcoxon signed rank sums

Tabb 8. Resuk of Chi Square and Student t-test anatysis of DlpmorpCiology Parameters in Expfgwd versrcs Ntmamwd Indmduafs. Ii I I 1 1 "

Chi Sq P value Not Value

Brachydactyty 3.578 0.059 4%' 0%'

New Diagnosis (afbr full chart 20.617 0.0001

t values P value Mean Percentile Rank r

HeigM Percentile 1 2.4138 0.0169 58 68

Weig ht Percentile 3-1 526 0.0019 62 76

1 Head Circumference Rrcentile 4.3019 . c 0.0001 58 77

II paipebr-a 38 L 47

denotes percentage of inâiuïâuais affecfed

Table 9. Resutts of Chi Square and Wilcoxon Sums Rank anaîysïs of Dysmorphology Parameters

Table 10. Cornparison of Dysmorphology Parameters by Diagnostic Categories based on the resuls of aie dy[u11orPhoIogy assessment alone, and the '

proportion of individuals mth abnomal f88fCJres per category (qualitative data), or mean percentile rank per category (quantitative data).

M W P W W ")rkmiir Pr(id FAS WIJ~ FAS

, a-m

Heiatlt Parcsntnt

WhigM rdurlmaruwnsnt 1

WeipM-Percanak

1 H e a d C - a - (ml

Head Cinwmlbranca P e m d h

OuterCarntidDmmeadm

MmlPacamleRrJr

27.751

9.6894

31.6U9

15.656

24.880

7.7342

66

40.

74

54-

72

8.6.

46

37'

50

53'

48

8.5.

0.0001

0.021 4

O.ooO1

0.0013

0.0001

0.0518

64

34'

75

54.

79

8.7'

22

29' 1

24

51.

25

8.1

test was used to test for signifiant differenœs betwwn the four diagnostic

categories baseâ on dysmorphology alme ("Normal", Dysmorphic (reasons

other than possible alcohol exposure), FAS, and Partial FAS). This analysis

revealed the significant dysmorphology parameters as being those which are

used to make the FAS diagnosis. Poar Cupid's bow formation was noted to be

statistically different between the groups (p=û.W2), with 12% of the v v m a l "

group (1 5/129) versus 50% (6H 2) of the FAS , and 33% (411 2) of the partial FAS

group king afkted (infonnrttion was not available for one FAS and one partial

FAS individuats). m in upper lip (p=0.011) was observed in 16% (21/1 31) of the

"normal" category in cornparison to levels of 42% (S12) and 506 (W72) in the

FAS and Partial FAS categories respectively. Reœssed midface, as judged by

diagnostician's impression, was also found to be significantly different

statistically between the groups (p<O.0001), 2% (3/124) of the "nomal" group

exhibited the Wall versus 36%(4/11) and 10% (1 MO) in the FAS and partial ÇAS

groups. With respect ta grawth parameters the following parameters al1 differed

significantly behneen the diagnostic categories: height perœntiles ( p=O.000 1 ),

weight psnentiles ( p= 0.0001 ), haad circumference crctual rneaswement

(p=O.W13), es well as percentiles (p= 0.0001 ), outer canthal distance

percentiles (p= 0.0002), palpebral fissure length, adual measufement

(p=0.0001) as well as percentiles (p=0.0001), and the ratio of palpebral fissure

length to inner canthal distance (p= 0.0006). In general, it was those individuals

with FAS, followed by those with partial FAS, who were shorter, lighter, had

srnaller head sires, had shorter outer canthal distances, shorter palpetml

fissure Imgths and smeller palpekal fissure length vefsus inner canthal

distance ratios (Table 10).

When the dysmorphology data k analyzed with regards to the n w

diagmstic wtmes ("Normal", Dysmorphic (not e-ed to be related to

alcohol exposure), Partial FAS, and FAS), using the Wilcoxon test, the results

previously mpated do rot change. That is, the dysmorphology parameters that

appear to be statistically sgiircant based on the analysis using the original

diagnostic catmes besed on dysmwphoIogy assessrnent results, are the

same parameters that appear significant in this analysis (Table 11). Similarly,

analysis of the mean percentile rank scores reveals that the FAS individuals are

the smallest, have shorter palpebral fissure lengths and shorter outer canthal

distances. In general it is the Partial FAS gmup who rank second lawest, as

might be expeded due to the presenœ of alwhd in this group as well.(Table

11).

Within the "Normal" diagnostic category, 38% had been exposed to

alcohol in utero. Cornparisans of aie exposed versus the non-erpased "nomial"

groups showed no statistically significant differenœs detected on any

morphometnc parameter at the p = 0.01 level. Howwer, height, weight, and

head circumference percentiles, appear to be borderline statistically significant,

for both total exposure and graded exposure levels for the normal category

(Table 12). Examination of the mean permtik rank scares indicete mat the

exposed group (and high exposure group, with respect to the graded alcohol

exposure analysis), are slightly (but not significantly) smaller than aie low

exposure and no exposure grwps (Table 13).

Table 11. Results of the analysis of the dysmorphology parameters by new diagnostic categories based on dysmorphology assessrnent and full chart review, and the proportion of affected individuals per category (qualitative data) or mean percentile rank scoreg per category (quantitative data).

Chia Pnkih Nam b- pww FAS 4 W- FAS

Ratio of Palpakil fi#uta kngthtolnnarcwhal A

Table 12. Cornparison of exposed and non-8xposed , as well as the amparison of graded level of alcohol exposure subgmups m i n the "Normalt' Diagnostic Category, with resped to borderline statisücally significant rnorphometric

Table 13. Mean percentile tank scores corresponding to the bordedine statistically significant (0.01 s ~ ~ 0 . 0 5 ) morphometnc parameters idenitified during analysis of the parameters by exposure versus no expsure, and graded levels of alcohol exposure in the "Normal" diagnostic category.

m0-d No Hiih Low None -re

Height Percentile 63 71 57 71 71

Weight Percentile 1 70 1 n 1 65 1 77 1 n Head Circumference 67 70 63 72 76 Percentile

Morphometric data from the "Normal" diagnostic category were used to

generate the normal Native cuwes. The normal category was fnst separated

and analyzed by sex Student t-tests were perfomied for each of the ten

morphometric parameters to determine if the data wuld be pooled between the

sexes for analysis, or whether the means between the males and fernales were

suniciently different, in which case two graphs would have to be generated for

each measured parameter, one for each sen The resuits of the hnro-tailed

student t-test analysis are listed in Table 14. As can be seen from the table. Vie

only morphometnc parameter that did not difFer significantly between the sexes,

and thus allowed for a pooled data gmph to &e created was the ON0 angle.

Graphs for each sex were construded for esch of the follmmng

parameters: height, weight, head circurnferenœ, palpekal fissure length.

philtrum length, imier canaial distance, outer canthal distance, hand length, and

palm length. The ON0 angle graph was creatd using pooled male and female

normal data. The graphs and mir conesponding tables are presented in

Appendix E.

Each graph is wmprised of two important areas. The shaded area

represents the range of measurement falling between the third and ninety-

seventh percentiles (except in the case of the head cirwmferenœ gnphs, in

which the shaded area ranges from the second to ninety-eighth percentile) from

the normal wrves previwsly desaibed in the literature, which are based

Table 14. Student t-test (No-tailed) fesults for comparing the means between the two sexes for each of aie morphometric parameters studied.

-

Fmmk

Var N Mean Var

25723 59 134-651 230-10

299.37 59 36.120 254.05

1 A1 1 59 52-77 5.527

primarily on Caucasian populations (NeIlhaus, 1968; Laestadius, 1969; Feingold

and Bo&, 1974; Thomas, 1981; Hall et al, 1 989). The second important

aspect to each graph is the sefies of f i e lines which represent the second,

sixteenth, fiftieth, eighty-fourth, and ninety4ghth percentile bounâaries for the

Native normal curves derived from the morphometric data collected in the

Normal categwy of this school-aged population. In the cases of palpebral

fissure lengths, philtrum lengths, inner canthal and outer canthal distances,

palm and hand lengths. the same shaded area appears in both newly generated

male and female Native graphs. This is due to the fact that, sex differenœs

were not observed in the previously reporteci literature and aius data between

the sexes could be paoled (Feingold and Bossert, 1974; Thomas, 1987, Hall et

al. 1989).

Paired Student t-tests were perfomed on the rnedian lines of the

previously reported growth m e s derived from Caucasian morphometric data,

and the newly generated Native normal curves, to detemine if in fact there was

a significant differenœ behneen the two elhnic gmps with respect to growth

parameters. Data used for the statistical cornparison of the medians is listed in

Appendix F. The resufts of the paired shident t-tests (Table 15) illustrate that

there were statistically signifiant difbrenœs (p 0.01) between the Caucasian

and the Native normal wwes for aie follhng parameters for both sexes: height.

weight, head cimmferenœ, hand Iength, inner canthal distance, outer canthal

distance, and ON0 angles. Females shawed bordedine statistical differences

(0.01 s p 50.05) for philtrum length and palm length with respect to compatison

between the Native and Caucasian medians. No statistical differenœs were

noted in eithw sex for palpebral fissure length, or for philtrum and palm lengths

in males. 6asd on the resuits pmsmted in Table 15 and M Figures 6 - 24

(found in Appendix E), it can be said that the "normal" schod-aged population

studied in this community are taller, lmavk, have larger head circumferences,

bigger hands (more pmcisely longer fingers), and have more wi-dely spaced eyes

as detemiimd by ina-eased inner and outer canthal distances than h i r

Caucasian counterparts.

Given that statistical difFerenœs were found between the Caucasian

noms and aiose generated in this study for the school aged Native population,

cornparisons of the morphometric data of the FAS (9 individuals) and partial FAS

( 6 individuals) group wra conducted using the newly generated wwes to

detemine if any dinerences would kt observecl with respect to percentile ranks

falling in the "abnomal ranges". Two individuals in the FAS group and one from

the partial FAS group were exduded from this aspect of study, due to the fad

that their age was greater than 14 years of age, and could n a be accommodated

on the newly generated Native normal graphs. Tables 16 - 19 present the

percentile rank results obtained when each of the morphometric parameter

measurements were compared on boai the Caucasian standard normal wrves,

and the newly gmerated Native ones. In the majority of cases, a m a s 8 in

percentile rank was noted when the morphornetric data were plotted on the

Native curves, as opposed to the previously established Caucasian wrves.

TaMe 20 provides a summary of the nurnber of FAS and Partial FAS individuals

whose pereentile ranks fell into the "abnomal zone" with respea to growai

retardation, telecanthus, shortened palpebral fissure size, inaeased philtrum,

hand and palm lengths when plotted on the Native versus Caucasian ames.

For example, 8 FAS individuals and 2 Partial FAS individuals were considered

growth retarded with respect to height (less than the tenth pemntile) on the

Native wrves, in camparison to 4 and 1 individual respedively, based on

Caucasian percentiles. Examination of other parameters showed that when

morphometric data was plotteâ on the Native wwes : 4 additional FAS diildren

were growth retardeci with respect to weigM (less than the tenth percentile), two

additional cases (aie FAS and one partial FAS) wwe miaocephalic (less than

the third percentile), and fine more children (2 FAS and 3 partial FAS) exhibitecl

extremely shortened palpebral fissures (less Vian the second percentile), than

when plotted on the Caucasian standards. Wth respect to philtrum lengths.

plotting raw data on the Native wrves lead to increases in the perœntile rank of

many of the individuals (619 FAS and 5s Partial FAS) as compared with their

previous ranks based on the Caucasian standards. The plotting of inner canthal

distances on the Native versus Caucasian standards decreased the nurnber of

telecanaiic cases (imer canaial distance above the ninety-eighth percentile)

observed (one FAS and one Partial FAS case were removeô). In many cases

plotting on the Native ame m a s e d the inner canthal perœntile rank for that

child (7/9 FAS, 516 Partial FAS ). This general trend of, deaeasing percentile

ranks whm Native data were plotted on the Native versus Caucasian curves,

was also obsenred for outer canaial distance percentiles(8/9 FAS, 4 6 Partial

FAS), palm (919 FAS, SE6 Partial FAS) and hand lengths (7s FAS, 6t6 Partial

FAS) for both FAS and partial FAS individuals. ON0 angles did not seem to be

M6cted uniramily in either direction when comparing the Caucasian percentile

ranks to the Native ones.

Table 15. Results of the Paired SMent t-test comparing the medians of the Nomal Caucasian growth curves to that of the new generafed Normal Native growîh m e s (for each sex).

P value P value (Males) (Fernales)

Weiaht

. Head Circumference

1, Hand L e m

0.0005

0.0001

Palm Length

0.002

0.0004

0.0042 0.0021

0-1 345 0.0236

Table 16. Cornparison of Height, Weight and Head Circumferenœ of FAS and Partial FAS Individuals, between Caucasian and Native Nonnal Standard Cuntes.

Nat ! m e 9688

2 50.5

2 48.5

36 482

16 48.4

Partial Fetal Alcohol Syndrome Growth Parameters, Caucasian Percentiles, and Naüve Pera I I t I 1 1 I 1 I 1

Table 17. Cornparison d lnner Canthal Distance, Outer Canthal Distance, and Palpebral Fissure Lengüi of FAS and Partial FAS Individuals, between Caucasian and Native Normal Standard Cuwes.

--Lem (cm)

I

Table 18. Cornparison of Philûum, Palm and Hand Lengths of FAS and Partial FAS Individuals, between Caucasian and Native Normal Standard Cuwes.

P r l i i l F u A l c d d s y n 9 a r i i . M a p h a r w b i c - , c r u r r ' u ~ , a n d ~ ~

070 68/12 m 1 -7 5s 10 8.5 IS 50 15-2 . 75 50

ûû? 89112 f 1 S - 45 55 7.8 25 7 14.3 35 16

1 28 62/12 f 1 .S 40 56 --- 7.5 15 10 15 75 35

2û6 89112 f 1.4 56 46 9 80 45 16 95 50

123 10 m 1.9 55 87 10 90 90 16 75 45 la12

180 11 f 1 -5 50 10.5 +97 84 18.7 a 7 84

Table 19. Cornparison of ON0 angles of FAS and Partial FAS Individuals, between Caucasian and Native Normal Standard Curves.

Table 2û. Cornpaison of the number of Individuals with "Abnomal" Percentile Ranks between ÇAS and Partial FAS data plotted on Caucasian versus Native Normal Gmwth Curves,

Number of FAS a d Parhl FAS Number of FAS and Partial individuals based on Caucasian FAS individuals based on

Cunres Native Cunres

Height belmu 10 th percentile 4 FAS, 1 Parüal FAS 8 FAS, 2 Partial FAS I

Weight below 10 th percentile 3 FM, 2 Partiel FAS 7 FAS, 2 Partial FAS

Head Circumbrence below 3rd 3 FM, 2 Parhl FAS 4 FAS, 3 Partial FAS percentiie

lnner Canthal Distance above 2 FAS, 1 Partial FAS 1 FAS, O Partial FAS 98ai percentile

Palpebral F é r e length below 5 FAS, O Parlial FAS 7 FAS, 3 Partial FAS 2nd percentile

Hand lemgth below 10th 2 FAS, O Partial FAS 7 FAS, O Partial FAS petcentile

Palrn length htow the 1ûth O FAS, O Partial FAS 6 FAS, 1 Partial FAS

4.1.1 Alcohol Abuse

Data collected in this study indicate that the overall rate of alcohol abuse

during PreQnancy in the study sample born in the years 1981 to 1990 was 46%.

Even more alanning is the fad th& 30% had been exposed to high levels of

alcohol prenatally, as assessed by an affinnaüve answer to the question

regarding alcohol as a reason for placement in the case of foster 1 adopted

children, or scores of two or more on aie TWW( test (Russell and Bigler, 1979).

These reportecl exposure rates are high when compared to other exposure rates

reporteci in the literatum. In a report by Dufour et al (1994) whidi surveyed the

drinkicg histories and kndeâge of the flsks of heavy drinking during pregnancy

in a group of women in the United States ranging in age from 18 ta 44, the rate

of risk drinking in this group of women of childbearing age was cited as 10% in

1990, where risk drinknig was considered to be msumptim of, on average,

more than one drink per day. Similarly, Serdula et al (1 991 ) reported on the

trends of alcahol conwmption in a grwp of pregnant women during the years

198s to 19û8. This sample of wornen (1 71 2) ranged in age from 18 to 45, and

represented 21 states in the U.S. Accordhg to this study, the rate of alcohol

exposure declined within this four year study perioû from 32% in 1985 to 20% in

1988, although no significant decreases were noted in the lower age bracket,

that is pregnant women under the age of 25 (Serdula et al, 1991 ). Wth respect

to levels of heavy drinking (on average two or more dnnks daily), only 0.6% of

pregnant women were noted to lm bavy dainken, and 2.8% were classifieci as

binge drinkers (consuming five or more dn'nks on one occasion). Striessguth et

al (1 983) noted a 42% rate of alcohol exposure at the first prenatal vise for a

sample of pregnant women in Seattle dun'ng the years 1980 to 1981. Little et al

(1 989) cite a heavy akohol eqmsure rate of 1.4% in a gmup of primarily

indigent wanen who attended prenatal clinics in Dallas, Texas, in 1987. Thus

from the data presented with respect to the Manitoba study, it appears that the

rates of alcohol exposure are rnuch higher in this community îhan îhose rates

found in ment reports on alcohol use in pregnant women. Particularly alarming

is the rate for high levels of alcohol exposure during pregnancy. Unlike the

study by Serdula et al (1 991 ), the rate of alcahol abuse in this community does

not seem to be deaeasing over time. Cornparisons of aie alcohol exposure rate

in those children born within the first half of the birth cohort versus the latter half

indicate that the rate of expowre appam to be consistent (44% versus 42%).

In one of the first reports of FAS, Jones et al (1974) stated that based on

the evaluatim of 23 childm whage rothers had histories of alcoholism, the risk

of FAS among heavy drinkers was 32%. Sokol et al (1 980)) in a prospective

cahort study, also computed a risk estimate for FAS among wamen who akised

alcohol heavily during pregnancy. Their rate of 2.5% was considerably lower

than that reporta by Jones et al (1974). In Abel's update on the incidence of

FAS (1995), which reviewed hnrenty-nine world wide prospedive studies, the rate

of FAS among heavy drinkers, as defined by consumption of two or more drinks

per day a five to s u drinks per occasion, was cita as being 4.3%. Data

presented in this thesis mxild indicate figures much higher than the most reamt

rate quoted by Abel. In aiis shidy, the rate of FAS ammg high alcohol

exposures (as detined in the previous section) was 16.3% (8149). if we include

the number of partial FAS children who had been expos8d to high levels of

alcohol prenatally, the rate of having a child visibly M8ded by alcohol imases

to 30.6% (1 5/49). How8ver. it is possible, given aie mtmpedive setf-reporting

method of alcohol exposure ascertainment used in this study that, the number of

heavy dnnkers may be an underestimate of the tnie figure. if we assume that al1

women ascertained in the stuây drank heavily during their pregnancies then, the

rate FAS per heavy drinker wwld dmp to 6.2% (1 1 M 78), or 10.1 %(181178) if

Partial FAS cases are included. However, these decreased rates are still higher

than those reported in the Iitmture. Thus alwhol abuse among women in this

community is a significant problem that has not decreased wiai time. This is

unfortunate as it is apparently leading to inwasing prevalence of FAS and

partial FAS afïeded individuals in the community at levels much higher than

those reporteci in the literature.

Why would such a discrepancy adse between the reported rates of

dnnking among women? One reason inflated rates may be observed is due to

the population under study. It has been stated that wmen who tend to engage

in long terni (aimughout pregnancy) risk drinking tend to be characterized as

k ing rninorities, who are of lawer educational levels and lower SES (Sokol et al,

lm; Day et al, 1993) Binge drinking patterns which lead to higher peak blood

alcohol levels, and tend to the fehis more adversely than constant

drinkiftg, seem to be infiuenced by age and cultue (May at el. 1983; Abel and

Hannigan, 1 995; Gladstone et al, 1 997). For example, Afncan and Native

Americans tend to participate in binge drniking more o f t a than their Caucasian

caunterparts (Abel and Hannigan, 1995). Thus if these ethnic groups are not

represented in a study, it is possible that the rate of drinking w l d be

underestimated. May et al (1983) noted drinking patterns and FAS prevalenœ

can also Vary greatly within an eainic group. In a study of three South-Western

Amerindian tribes in the United States (Plains, Pueblo, and Navajo), May et al

(1 983) illustrated almost a ten fold diimnœ in the prevalence of FAS between

the tribes with the highest levels k ing noted for the Plains tribe (1 9.5 per 7000)

versus the Navajo and PueMo cultures (2.5 and 2.7 per 1000 respectively).

Previous studies have also illustrated that drinking patterns were highest in the

Plains culture (50 - 55%) versus the Pueblo and Navajo tribes (1 3923%)

(Whitaker, 1962; Whitaker, 1982, Levy and Kunitz, 1974).

It is adviowledged that caution must be used when comparing rates of

drinking or heavy drinking among women. It is possible that due to fears of

stigmatization or pnishrnent women may underrsport the levels of alcohol

consumption duflng pregnancy. If this is ocarrring, then we would expect the

numbers citeci in the literature to be underestirnates of the true level of drinking

in women. Also, many studies use different definitions for heavy alcbhol

cansumption. Some may repart alcohd consumption by daily intake, which as

Abel (1995) has stated, is not very accurate. as many people tend to dnnk on

occasion, instead of daily. Some studies may define heavy alcohol consumption

by binge dtinking. mus when comparing reparted rates of heavy alcohol

exposue, one must be aware thet different definitions of heavy alcohd intake

are used in each study and, for that reason, cornparison of these rates between

studies may not a h y s be appropriate.

4.1.2 Ptevaience of FA$ and Partial FAS

Although epidemiologicel data conceming alcohol related birth defects

and FAS in general are limited, the numbers in the Iiterature illustrate one thing,

that the prevalence of FAS varies not only between dfierent countries and

ethnic groups, but within them as well (Abel and Sokol, 1987; Abel and Sokol,

1991 ; Abel, 1995; May et al, 1983). Estimates of FAS have ranged from a world

wide incidence of 1.9 per 1,000 live births in 1987 (Abel and Sokol, 1987), to a

revised estimate of 0.33 cases of FAS per 1000 Iive births in 1991 (Abel and

Sokol, 1991 ), to an updated figure of 0.97 per 1000 births in the general

obsteûïc population as of 1995 (Abel, 1995). The first of these -dies by Abel

and Sokol was based on review of 19 prospective and retrospedive worldwide

studies, M i le the second two estimates wsre based solely on prospective

studies. FAS incidence was twenty ümes higher in the U.S.A. than in Europe

(1 -95 versus 0.08 per 1000). and within the United States itself a ten time higher

rate is obsenred in areas comprised of low SES individuals uf African American

or Native Arnerican background, as compared to middlelupper SES Caucasian

backgrand areas (2.29 vs 026 per 1000) (Abel, 1995).

Relating to ethnic specific FAS epidemiology, are the studies amceming

FAS in Amerindian and Canadian Aboriginal populations. Data on these

particular ethnic groups are even more limited. Abd states that Native Amencan

populations mwe not induded in the 1995 incidence estimate, due to the la& of

availability of prospective data on such cornrnunities. However, studies in

Canada, partiailady on the West Coast. have indicated that FAS is a major

problem affecting subgmups of the Canadian Aboriginal population. Wong

(1 983) in an unpublished study report FAS rates ten fold higher among the

Native versus nonNative population of British Columbia during the years 1973 - 1980 (4.7 versus 0.4 per 1000). H i l e the highest reportecl prevalenœ rates for

FAS are those reported by Robinson et al (1987) at levels of 190 cases per 1000

Iivebirths, almost a 200 fold increase over the 1 995 worldwide estimate. In mis

Manitoban study, the prevalenœ figures do not reach the same magnitude as

Robinson et al's (1987). However, they are extmmly high in cornparison to the

worldwide rates. The absolute minimum prevalenœ figure calculated using the

MSB population sue as 352 individuals, and assuming that no other cases of

FAS would be found in the 49% af the population rot studied, leads to a

prevalence rate 32 fold higher than the world estimate (31 per 1 ûûû children). if

one l a s at the most likely estimate of prevalenœ for this study, where it is

assumed that the shrdy sample is a random sampling of the population, then the

prevalenœ figure increases to 62 cases per 1000 driîdren (64 fold higher than

the world estimate).

This stuây cites the rate of FAS affeded individuals to be 6.2% (1 111 78)

of the stuây population. anâ the rate of partial FAS individuals to be 3.9%

(7/178). Therefore it can be said that alcohol has adversely M8Cfed at least

10.1 % (1 81 178) of the school aged population of this community. This number

is not unique, and alaiaigh not quite as high, is in the same order of magnitude

as other previwsly reporta rates in Canadian M g i n a l populations in British

Columbia (18.5 %, Robinson et al, 1987) and the Yukon (42.5%, Asante et al,

1 985).

Although the figures are high, they may still be an underestimate of the

true prevalence rates in the commwiity. Fadm such as refusal to participate in

the study, absence from school on the dysmorphology assessrnent days, and

transient movement on and off r e m e , may have caused researdiers to "miss"

some cases. Even if ascertained, given the nature by which the diagnosis is

detemiineb-primarily a quaalative opiniw+thm may be some individuals who

have been misdassifieâ. It was intended mat, by having only one individual

experienced with FAS diagnosis assesses the children that this bias and biases

with respect to dmrent criteria being used to detemine FAS diagnosis cwld be

avoided. A third bias noted in many studies is the stereotypical belief that

Natives are at increased risk for heavy drinking which may lead to the labelling

of more children. Kndedge of the alcobI exposures status prior to the

dysmorphology assesment of a Native drild rnay also lead to over diagnosis. It

was hoped that, by blinding each investigator to the exposure histories of the

children and eliminating cases with positive dysmorphology where exposure

could not be doaimenfd, biases stetnming fran the stigmatization œntering on

the stereotypical belief of higher alwhol abuse rates in Natives, would be

minirnized.

In exarnining the dysmorphology results based on diagnostic classification

(both based on dysmorphology alone, and based on full chart review), it is not

surprising that growth parameters such as decreased height, weight, and head

circumference, and certain craniofacial landmarks-shortened palpebral fissure

lengths, poorly forrned Cupid's bow, thin upper lip, mœssed midfaœ, and the

ratio of the palpebral fissure length to the inner canthal d i s t a n ~ r e all

statistically significant, as these are the prirnary items incorporated by the

Dysmorphologist, when making the diagnosis of FAS. M a t is interesting is the

identification of significant differences mai respect to many of the previously

listed items when one divides the study population not by diagnostic categories,

but t'ather by positive or negative alcahol eicposue histories, or by graded

prenatal alcahol exposure. It is when items appear to be significantly different

behNesn the different exposure groups that validation is given to the items used

for diagnosis, as items tnily reflecting the d b c t s of alcohol an aie developing

fetus. In this study, aie growth retardation categones, rnidfaœ hypoplasia. and

palpetmil fissure lmgths were of primary importance.

Many sbidies have ewamined in- the diflenmt growth parameters

(height, weight and head cimmferenœ) (NeIlhaus, 1968; Merlob et al, 1984;

Hall et al, 1989) and amiofadal landmarks adated mth FAS diagnosis

(short palpebral fissure length and microopthahnia, widely spaω eyes, long

smooth philtnim, thin upper lip, long reœss8d midface, short uptumed nose,

flattened nasal bridge) (Hyme. 1929; Laestadius et al, 1969; Jones et al, 1978;

Fuchs et al, 1980; Merlob et al, 1984; Clarren et al, 1987; Olsen et al, 1995;

Astley and Clarren, 1996; Johnson et al, 1996) in populations of both affecteci

and unM8Cted individuals, to detemine alwhol's effed on each of the features.

Studies have consislently ilhrstmted growth tetadation as a hallmark

feature of FAS, or in general alcohol exposure (Hanson et al, 1976; Little et al,

1 977; Mills et al, 1 984; Lairoque, 1 992; Day et al, 1 994 ). Studies by Little

(1 977), Mills et al (1 984) and Day et al (1 994), report that weight (at birth and

wrrent ) after correction for confounding variables (such as matemal cigarette

smoking, SES, etc.) is decreased significantly with heavy alcohol consumption

during pregnancy. Day et al (1994) suggest that weight is aff8Cfed by alcohol

exposure during one or al1 of the trimesfers, with the higbst deficits noted for

exposure during the third trimester. Similady, animal mode1 studies have also

doaimented such growth retardation in mice (Middaugh et al, 1988; Middaugh

and Boggan, 1991 ). Day et al (1 994) also note alcohol exposure significantl y

affects height (prirnarify during the firsf and third trimester), head ciraimference

(second and aiird trimester), and redUCBC1 palpebral fissue sire (first and third

trimesler). For thid trimester exposures. the reduced palpebral fissure she is

prabebly mediated by smaller head CifcumfereMse, Mile e-ures during the

first trimester alone are mediated by direct teratogenic action d alcohol on the

developing eyes (Dey et al. 1994).

In our study. growth retardation as doaimenteci by height and weight

belw the tenth pemntile, and by head ciraimfmœs below the third

percentile was also shown to be significantly different between those prenatally

exposed to alcahol versus the unexposed segment of aie schoolaged

population under dudy. Our figures for the proportion of FAS individuals

expressing the characteristic hallmark fieatures are similar to those previously

reported in the literature. For example. in a study by Hanson et al (1976) in the

United States, 97% of their FAS patients exhibM postnatal growth retardation,

whiie 93% were miaocephalic. Robinson et al (1987) in a stuây of FAS in one

Canadian Aboriginal population in British Columbia noted growth retardation in

91 % of FAS individuals and 91 % rate of miaocephaly in these afkted subjects.

Our Manitoba study of FAS in a Native community cites growth retardation

figures of 44% for heigM, 33% for weight. and 33% for miaocephaly when the

data is plotted against the Caucasian standards. On the surface the sample in

this study does not seem to exhibit the same level of growth retardation as the

previously reported data suggests. There are two possible explanations: (1 ) that

our numerator is small in comprison to those previously reported, as this study

only has one mrth and ane half of the FAS patients reportecl in aie two

previously mentioned studies respecüvely (Hanson et al, 1976, Robinson et al,

1987); and (2) this particular population does not confonn 10 Caucasian standard

gr& airves. The Caucasian and Native school-ageâ populations dHer

signifieantiy with respect to mir growth parameters. If cornparisons are made

based on percentile ranking against the n o m for this Native population, the

growth retardation rates for FAS ind~duals in this stuôy mxild be 89% for

height, 78% for weight, and 44% for microc~phaly. These figures are similar to

the previously established levels.

The present study is also rerniniscent of previously reported literature

desaibing charaderistic facial feakres that are associateci with alwhol

exposure in uteio, and used in the diagnosis of FAS. Some d these features

indude: miQOOPMh8lmia andla short palpebral fissures, hypertelorhm, long,

poorl y developed philtnim, epicanthal folds, midface hypoplasia, flattened nasal

bridge, and a short uptumed nose (Jones and Smith, 1973; Hanson et al, 1976;

Clarren and Smith, 1978). Features which were found to be signifcantly

difrent belween the exposeci (graded) and unexposeci grwps in this study

were: palpebral fissure Iength. reœssed midlace, and kachydactyly.

Craniofacial landmarks which were amsidered significantly different between the

diagnostic categories included: poor aipicYs bow formation, aiin upper lip,

recesseâ mi- (based on the dysmorphologist!~ impression, not basd on the

ON0 angle measurement), palpebnl fissure length, and the ratio of palpebral

fissure length to inner canthal distance. Data presented in this thesis state the

rates of observance of these chamteristic FAS craniofacial landmarks in the

FAS diagnostic categofy as being: 50J6 pow Cupid' s bow fomiatïon, 42% thin

upper Iip, and 36% recessed midface. Philtnim formation was not msidered

significantly d i f fmt between the different diagnostic categodes. These figures

are somewhat lower than the previously reported rates in FAS individuals. 65%

for midfaœ hypoplasia in the Hanson et al (1 976) report, and 91 % poor philtnim

formation in the Robinson et al study (1 987). With respect to shortened

palpebral fissure length, cornparisons against the Caucasian noms provides a

rate of occurrence amongst FAS individuals in this study to be 56%, while

cornparison against the Native ames provides a rate of 78% in the FAS cases.

The latter estimate is considered to be more in-line with the previously reported

rates of 92% and 86% by Hanson et al (1976) and Robinson et al (1987)

respectively. However. observed differenœs b e W n the reported rates of

many of these characteristic aaniofacial features may be an artifad of the

qualitative or descriptive nature of assessrnent for such features. Thus the

observed diffemats may be a refledim of the "eye of the beholder" and not a

true quantitative differenœ. The palpebral fissure IengtMnner canthal distance

ratio for o u FAS diagnostic category wes 0.74. which falls in the middle of aie

reported range by Astley and Clarren (1995) of 6082% for FAS individuals.

Reasons why FAS established craniofacial features such as philtnim

length, hypertelorism, and epicanthus do not appear to be statistically different

behnieen the diagnostic categodes axild be due to the f k î that these items may

be M a e d by ethnicity. In the Manitoba study, fhe subjeds w e of a single

ethnic background and were not compared against an outside control gmp,

whose ethnicity would be varied. However, in the original study of FAS by Jones

and Smith (1 973), eleven FAS patients were identifid, six of which were of

Native Arnetican origin. Thus it is perhaps possible that features such as

epicanthal folds could have b e n considerd indicative of FAS due to the fa&

that they appeared in this partiwlar ethnic group, who represented roughly 50%

of the study sample, and not due to its unconditional occurrence in al1 FAS

patients irrespective of race. it is for these reasons that Striessguth et al (1 988)

wams against cornparisan made on ethnic-specific noms, which are not specific

to the ethnic group understudy.

c Many reports in the Iiterature have made note of the potential biases of

camparing Native or other eainic gmup morphornetric data against normal

growth m e s primarily generated by data collscted in Caucasian populations

(Robinson et al, 1967; Streissguth et al. 1988; Bray and Anderson, 1989; Abel

and Sokol, 1991 ; Abel, 1995). These conœms have been brought to light by the

fad that there appear to be distinct differences *th respect to certain features

and growth parameters behnieen the gmps- For example, Afiican Ametican

children tend to have lawer birth weights than Caucasians in the United States

(Feinleib, 1 989), and it is postulated that this may cause African American

children to be at higher risk for FAS diagnosis based on the tral of demasecl

birthveight as compared to the Caucasian noms. Striessguth et al (1 988) note

that no growth charts specific to Natives have been generated and that given the

obsenred difFerenœs behneen the birVnneigMs of American Americans and

Caucasians, it is possible that there could be substantial d R m œ s be-n

growth parameters both at birth and postnatally for Natives and Caucasians.

Fuchs et al (1 980) have also examid &nic d i n e m s with respect to

one craniotacial feature: palpebral fissure size. Statistically significant

differenœs wwe noted when palpehl fissure sires were compared benNeen

groups of African Americans, Hispanics and Caucasians. Both the African

American and Hispanic populations had significantly larger palpebral fissure

sizes than their Caucasian counterparts (Fuchs et al, lm). Tennes and

Blackard (1980) illusttated that epicanthal folds are more m o n among

Natives Americans, African Americans and Hispanics. In the study of FAS

among a group of Canadian Aboriginals by Robinson et al (1987), it is sWed

mat "the presence of epicanthic folds and other anthropomorphic features of

native lndians limited the cwnparability of these measures to standards reported

from other research". Other docurnented differences between the "norms" in

one ethnic group versus another include: depressed nasal bridges and

retroverted ears (common in Afncan Americans) (Tennes and Blackard, 1980;

Ornotade, l99O), and the antimongoIoid slant cornmon in some Native

Arnericans (Abel and Sokol, 1991).

Given that there are signifiant dinerenœs between ethnic groups with

respect to gmw&h parameters and certain craniofaaal features, it is less useful to

compare them against Caucasian normal standards. Unfortunately, the

Caucasians are the only group for Mich standard morpbometfic data has been

analyzed to generate many of the standard growth curves noted in the literature.

Thus. l one wants to compare a gnnip d diildren against noms, these are the

only ones readily available with which to compare the collected data. This can

be problematic, especially in the case of Native Arnericans "because certain

features ttiat are normal for their airm reference gmup are atypical for whites",

such as shortened palpebral fissure size and epicanthal folds (Abel and Sokol,

1991 ). Thus a Native American child may be at inaeased risk of being

diagnosed as FAS, due to their subsequent "[evaluation] against a background

of Caucasians" (Abel, 1995). Abel (1 995) as well as Striessguth et al (1 988)

caution that, if appropriate race-standardired n o m are not used, FAS rates in

these cammunities may be inflated, rot due to an aclual increase in the number

of affeded individuals, but due to the impression of an inmease of WWed

individuals, based on misattribution of m e of the features used for the

diagnosis of FAS as being due to al- exposure, and not due to nonnal

ethnic variation. However, it is also possible that the Native population may difter

in the opposite direcüon from the Caucasian standards. leading potentially to

missed diagnoses in the ethnic graip.

The present study of FAS in a First Nations Community in Manitoba, is to

ouf kndedge, the first of its kind to actually doaiment statistically signifiant

differenœs between the "nomaf" component of the Native school-age

population studied, and the previously report& standard wrves based on

Caucasian data. This study has confirmed suspicions that the two populations

d#er significantly, and thus enforce wamings against the use of normal wrves

not specific for the ethnic grwp under study. Data presented indicate that the

school-aged population under study are taller, heavier, have larger head

cirairnferences, longer fingers, and more widely spaced eyes than the

Caucasians used in the literature standard wrves.

Data collected as part of the "Normal" diagnostic category, were used to

generate the Native noms, based on the fact that al1 individuals induded in this

category do not exhibit growth retardation, characteristic facial features of FAS,

or other 'Lbnonnalities". ft is ûue h ~ v e r , that the "Normal" category does

wntain a number af individuals who have be8n exposed to akohol. It is

passible Mat indusian of aiese individuals in the analysis for Native nom

development . ma y con taminate the normal CU rves generated. Hanrever,

statistical analysis camparing al1 rnarphometfic data between the alcohol

exposed "normal" group versus the nonexposed "normal" group do not support

this concem, as no statistically signifiant difference was obsewed for any of the

adual morphometric measurements btween these two groups. Thus, since the

exposed ''normal" individuals appear phenotypically normal, and do not differ

sbtistically fmm their umxposed counterparts, theif moiphometric data has

been included for the development of the Norrnative Native arves.

Given that the Native population wider shidy was l a w , on average, than

what is reported in the Caucasian based literature, sorne FAS or Partial FAS

children could be misdassified, due to failure to meet aiteria such as growth

parameters below the tenth percentile when compared to the Caucasian

standards. In order to test this hypothesis, comparisons of the FAS and Partial

FAS individuals against the standard curves generated using normal peer data

were conducted. In general, when companng against a group of their pers the

perœntile ranks of these individuals decreased. Iweased number of

individuals with 81dassic8a FAS traits were obsewed. Some of these features

included heights and weights below the tenth percentile, head cirwrnferences

belaw the third picentile, and shortened palpebral fissure length (less than the

second percentile).

Thus the data presented in the Nonnative Data section of this thesis are

important as they provide empirical evidence to support previous wamings

against interiacial nom comparisons. Even though these data are, we believe,

the first of its kïnd to descriôe gmwth and craniofacial rnorphometric standards in

a group of Aboriginal school-aged children, caution shaukl be u s d wiai

respect to genenlidng ôeyond the .top of these data. Although this was a

populaüon-based study, aie numbers used to generate the curves are small, and

thus a larger sample wwld be mquired to Mher support the trends noted here.

Also. as it is true behnieen broad ethnic groups, it is probable that the growth

parameters reported hem, may dïer greatly with respect to different Aboriginal

groups, and thus it would not be m a t e to comgaib ail Natives wnrt

theme standard.. Given that there is much inter-tribal variation with respect to

morphometric parameters, the idea of creaüng one single set of Nonnal Native

cunres, is most likely impossible to attain. Also, even if Native standard wwes

were developed for each tribe, the probfem Ulen becomes ensuring that the

proper "tribal wwe" is used in the appropriate population. tf one applies a

"tribal cufve'' to the morphometric panmeters of a different tribe it is expeded

that the same Mect would be observed as comparing them on a Caucasian or

any other ethnic group wrve, that is the potential misclassification of children,

which in tum infiate or defiate the true prevalence of FAS for th& partiailar tribe.

For these reasons, it wwld be impradical and impossible to achieve a single

Native standard wrve for the morphometric parameters described in this thesis.

This study, however, does provide a stafting point for a relatively neglected area

of research. the desaiption of normal native morphometric parameters.

c Abel (1 995) has stated that "FAS is not an equal opportunity birth d8f8d".

This appears to be true. Both data pfesented in this report as well as numemus

other reports indicate that Native Arnericans and Canadian Aboriginals seem to

be at increased risk af having a child with FAS. Suggestions as to why Wis may

be so have varieci. One hypothesized reason is that Native Americans and

Canadian Aboriginals may have a -c susceptïbility for FAS, that is they may

be lacking certain enzymes which help deai alcohol fmm the mothets system

More 1 traverses the placenta and r e m s the developing fetus. Sorne of the

enzymes hypothesized in this mode1 indude: alcohol dehydrogenase (ADH), the

enzyme respansible for metabolizing alcohol to acetaldehyde, and the presence

of the inactive fonn of aldehyde dehydrogenase (ALDH22), which leads to

accumulations of acetatdehyde in the mothets system. However, no scientific

evidence exists to suggest that there is a predisposition for ceratin isofons of

ADH to be specific to Natives, nor has the sci8ntific community found cases of

ALDHZT in any ethnic gmup other than Asians (Bosron et al, 1980; Bosron et

al, 1983; F austman et al, 1992; Ooedde et al, 1992; Cooper, 1993). Thus

genetic predisposition based on these genes seems an unlikely mode1 to

account for the higher frequencies of FAS in these populations.

A second hypothesis has been that problem drinking is more common in

the Native Ametfan and Canadian Aboriginal populations compared with the

Caucasian population. This idea also does not ring tnie, as the Centers for

Disease COnffO1 (CDC) dxmed in its 1988 sunrey, it is wwnen who are white,

more educated, of a higher incorne level, married and smoke that are more likely

to drink duinig pregnancy (CDC, 1995). Day et al (1993) alao note that

abstention rates are higher for women of Aftican American, Native American and

Native Canadian descent, yet, rates of heavy drinking during pregnancy are

higher for Aboriginal and African American gmups than for the Caucasian (Day

et al, 1 993; InsaMe of Medicine, 1 996). Hawever, in many of these studies,

race has been confounded by low SES, which is thougM to be the primary

reason FAS is observed at higher rates in these comrnunities rather than any

genetic predisposition (Abel, 1 995; Abel and Hannigan, 1 995).

Abel and Hannigan have put forth a plausible model for FAS susceptibility

which takes into account many of the preexisting data derivecl from the

numerous animal mode1 studies, and matemal risk factor studies found in the

literature. They propose that, in the presenœ of alcohol, there are two factors,

permissive fadm and provocative factors that intBCaCf to put the fetus at risk for

FAS. Permissive factors are defined as "predisposing behavioural, social, or

environmenbal charaderistics that produce certain biological conditions, [that] ...

in conjundion with heavy drinking inuease fetal vulnerability to alcohol's

teratogenic M8dsm0 (Abel and Hannigan, 1995). Provocative factors are "

biological conditions resulting from the permissive fadws which create the

intemal milieu responsibk for the increased fetal vulnerability to alcohol at the

cellular level" (Abel and Hannigan, 1 995). Permissive feors include: alcohol

intake patterns, faœ/socioecmomic status, wlnire/eainiaty, and smoking. They

propose that certain cultures have diffmnt patterns of alcahol intake. For

example, Caucasian women are more likely to drink at a constant level during

the week, while Native American m e n tend to drink in episodic bouts (binging

consumption of 5 or more drinks on one occasion) (May et al, 1983; May et al

1 989). It is those wmen who consume alcdiol in binge fashion that have

higher peak blood alcohol levels(BAL). than do w~nen who consume alcahol

steadily over time (Pierce and West, 1986; Bonthius et al, 1988; Sampson et al,

1 9û9; Striessguth et al, 1 989; Striessguth et al, 1 994). Thus by this theory, it is

the higher peak BAL (provocative fador) which puts Native children at higher

risk for FAS, due to the cultural pattern adated with alcdiol consumption

(permissive factor).

Similarly, as was stated before, it is SES rather than ethnicity that seems

to predispose t m r d s development of FAS. Low SES (permissive factor) is

proposed to lead to poor nutrition, increased exposure to other toxins in the

environment (such as leaâ), cause increased psychological stress, be

associated with higher parity, and increased smoking, al1 of which can act to

exacerbate aie tmtogenic M8ds of alcohol (Abel and Hannigan, 1995). They

propose that it is the biological changes (placental dysfunction, endocrine

changes in the mother, and other biochemical and physiological changes) that

result due to those conditions induced by low SES, which ultimately increase the

susœptibility of the fetus to the damaging Meds of alahol. Hypoxia is thougM

to be the primary factor induced by aie interadion af the permissive and

provocative factors. It initiates a cascade of cellular events leading to cel!

damage, inappropriate diffimnüatiation, prolifi3ratian, migration andlor regulation

of cell growth as well as, frae radical oxidative stress, which disrupts cellular

integrity (Abel and Hannigan, 1 995). Therefore, although alcohol is a necessary

factor for the development of FAS, it h not sufficient as there are a whofe host of

oaier factors which also must contribute ta the temtogenic eff8cts of alcohol on

the developing fetus (Abel and Hannigan, 1995).

Based on this mode1 it is clear that Aboriginal women may be at increased

risk for many of the permissive factors which tend to focus more around low SES

than ethnicity. It is probably these factors related to poverty and culture, in

combination with episodic, binge alcohol consumption which puts Aboriginal

diildren at increased risk for FAS.

The research presented in this thesis is important for a nmber of

reasons. Firstly, data collecteci and premted in the dysmorphology

assessment sedion of the thesis support many previously established reports on

the phenotypic features of individuals with FAS. These data also identify and

support concems about using aaniofacial charaderistics for diagnostic

purposes whidi are nmat for one ethnic gmp, but abnormal when compared

against Caucasian standards, or any other non-specific data. For example,

Afncan American children naturally have palpebral fissure lengths which differ

from Caucasian noms (Fuchs et al, lm), Mile epicanthal folds are considered

normal in the Native population. Thus aiere may be an inuwsed number of

FAS diagnoses in these communities when these features are considerad of

prime importance in the diagnostic gestalt. The data presented strongly

support the need for the creation of eainic specific noms, and perhaps the

development of ethnic neutral diagnostic aïteria for FAS in order to prevent

underestimation or ovefestimation of FAS due to natural ethnic diversity with

respect to craniofacial features and growth parameters. However, the idea of

king able to create one standard set of Native noms, is as impossible as

creating one set of morphometric noms for the entire human race. Just as each

ethnic grwp varies with respect to morphometnc data, so do the various

Aboriginal groups.

Finally, the presentation of the data contained in the Normative Cumes

section of this thesis provides ernpiric evidence supporting wamings such as

those made by Stiessguth et al (1988) conœming the inappropriate

cornparisons of one ethnic group against noms developed for a second race.

Data presented in this stuc& support aie hypothesis that growth patterns

between Natives and Caucasians differ significantly. Thus it is not appropriate

to compare Natives against Caucasian m s as it will inflate or M a t e the

actual FAS prevalenœ reported, based on which parameter is being examined.

4.6 Fu- Re8earch T-

The research describeci in h is thesis has broken gmund for a number of

spin df studies. It has suggested aie need to develop race neutral diagnostic

criteria for FAS diagnosis, such that normal ethnic variants wïll not be identified

as an abnormality, and thus incfease a childs chance of being diagnosed with

FAS. To further this approach, studies into other normal Native sdiool-aged

populations would be important, to further the work initiated in the Normative

wwes sedion of the thesis. lt is acknowledgd that the curves were generated

using a srnall number of individuals, fumer study into this area, could eventually

allow for the creation of reliable Native ames for mis puticular Native ethnic

group whidr cwld be used to allow for camparison of the growth of the Native

children against their peers, rather than against Caucasians.

Thirdly, the epidemiology section of the thesis has unequivocally

identified this community as having a problern with FAS. The question now

becomes, what can be done to fix this problem? Givm that the rate of alcdrol

exposure does not seem to be decreasing, it is possible that the situation could

becorne worse in the community before it gets better. One way to improve the

situation hem, is to facilitate prevention of FAS, through intensive alcohol

awareness ducation efforts aimed at the youth, in partiwlar the young women.

It is these individuals who have perhaps through observation of their mothers,

aunts and other female relatives, acquired their drinking patterns, one of which

is drinking during pmgnancy. It will become important now to stop this cycle, so

that a second generation of Meded childen can be prevented. Pemaps this

type of education can be integrated as part of an ongoing couse within the

s c h d s wmiwlum, similar to sex educaüq w drug awareness course, or it

could fall under the responsibility of local health workers as a series of special

seminars within the community.

With respect to the individuals already a W e d by prenatal alcohol

exposure, it is important that they be identifid. KnowIeâge of oie FAS or Partial

FAS status of a child would allow the school to apply for extra hinding needed in

order to support the sWal education pograms that will be necessary to

develop in order to educate the FASI partial FAS individual at their appropriate

level.

Many responsibilities such as control over health care and education

have b e n transferred to some Native cornmunities as part of a Native self-

govemment movement in the past few years. Thus it is now important for the

communïties to identify and develop solutions or ducahive efforts to help

prevent the problem.

APPENDICES

Appendix A Consent foms used in the FAS Community Study on one First Nations Community in Manitoba.

Fetal Alcohol Syndrome 1 Fetal Alcohol ERact Community Study Consent Fom

Researchen from the University of Manitoba. with approval and support of the Band Counul, will be coriduding a stwly in the comrnunity over the summer and fall of 1995- The purpose of this study b to as- a l school ageâ children in the comrnunity bom between the yean t9811990 to detemine if rchod diflicultiss and behaviouml pmblems in childmn can be adatd with events in the pmgnancy, such as emsure to alcohol or dmgs befom bnth. By condUdlUdlng this rtudy ws hope to aquirs a M e r understanding of the 8- of early alcohol exposure on academic (school), behavioural, and s e l pr fmanœ. as d l as its d lWs on the child's physical cha~sd~stics- This study will help identify the prevalence of Fetal Alcohol Syndrome within the community and help i d e m the spacial m d s of îhese drildren-

The study will involve an interview with mothers in their homes conœming family histories, pregnancy histories. alcohdldfug use, and a rating of the chilci's behaviour, which mll take approximately 45 minutes to one hour to amplete. A rating of the child's behaviour by his/her teachq and an asseument of the childs academic (schod) abilities on a standard test by a trained person at the school wi l also be condududed. A partial physical examination of the chi# wil k done by 0i. Chudky. This will take plaœ at the schoof. Dr. Chudiey will take a pidure of the child's face as part of the examination. The picture will be kept in the child's confidential fik and will not be made public in any way. Dr. Chudley will examine the chiid's head, nsdr. chsst, badr, abdomen, hands and feet, and will also assess the child's height and weight. The examination should take approxirnatety 15 minutes and will involve minimal diScOmfORScOmfOR It indude blood drawing, X-rays, or any other painful tests. Fdlwing the study a written statement will be provided to p u outliniq the msults of the study.

All infornation obtained as part of this study will be treated with abdute confidantiality and anonyrnity Ml be pmsewed. If abnonnaliw am found the results of your child's asseamnt will be disarssd with you by one of the dodon. and if mquimd, with your permission, referrals to the appropriate agencies will be provided. If the results of this study an, pubîished no individuals will be idenMM. nor piducw used. Your paRicipation in this study is voluntary and you may withdraw your child from the study at any time without jeopardizing his(hsr p m m t of Mure medical cars or ducation.

If you a g m to participate and enroll your child in the above study please sign below. We thank you for your coo-on.

I understand the purpose and nature of the Fetal Alcohol Syndrome 1 Fetal AIcohol Effect Community Study as explained to me by 3

and I agree to participate and enroll in the study.

Signature of Parent I Legal Guardian Date

In the event that this study reveals that your diild has FASIFAE or other academic difficulties or physical ebnormali. this inforniath oould be used by the school to help set up sm*al programs aimed to help your child with their difficulües, Thus in the case that an abnonnaMy is founâ in your cMd we are asJcing your pamiimiori to inform the schooI of this information, so that they can bator hdp your child. This information will be used strictly for academic purposes only.

- If you agreo wiîh the above staternent and would Iike us to infom the school if an abnormality is detected in your child pieam s$n below. I understand and agme to have 's indMdual aammemt resuîts disciosed to the schwl in the evmt mat an abnomali is detected through the Fetaf Alcohol Syndrome / Fetal Alcohol Ened Community Study.

Signature of Pamnt / Legal Guardian

If you Dû NOT a g m with the abow staternent and DO NOT wish us to infonn the school if an abriormalïty is detected in your child please sign belw- I understand the above statemnt, but 00 NOt give permission for

's individual assessment results to be disclosed to the school in the event that an abnomality is detected through the Fetal Alcohol Syndrome / Fetal Alcohol Effect Community Study.

Signature of Parant 1 Legal Guardian

Fetal AIcohol Syndrome / Fetal Alcohol Efféct Community Study Hospital Records Consent

One of the criteria used to diagnose FAS is gmwth defiaency in children. Part of the physical examin8üon that Dr. Chudky will perfomi on your drild will involve taking their height, wigM and their head circumfemnœ. We would Iike to be able to compare mir levels of growth, with their grOWfh su^ at bkth, to determine if cMldren exposexi to alcohol befbm biM d n w to remah rmell for Wr aga h ofder to do this we requin your permission to examine your child's medical files at the hospital whem they wre ban. All infonnafion obtaind f m your child's file will be icept confidential and anonymity will be preserved.

if you agm to let Dr. Chudley, Dr. M o W and their ~ s ~ ~ ~ l * a t e s have acœt to your child's medii l records at thsir birth hospital for the p u r p o ~ of colMng the pnviously mentioned irrfomation to be used in the FAS/FAE Community Study please sign below.

Thank you for your cmpeo r i .

1, , understand the above statement and give permission for Dr. Chudiey, Dr. M M and h * r a-ates to have access to

's medical files at hospital to obtain information for the purpose of the Fetal Alcohol Syndrome / Fetal Alcohol E f f d Community Study. I acknowfedge that all infornation obtained fmm the file will be trwated with absolute Confjdentiality and that anonyrnity will be preserved.

Signature of Parent/ Legal Guardian Date

Appendix B. Matemal Interview form used in the FAS study of one Manitoba First Nations Community.

Petal Alcohol Syndroie / F e t a l Aïwhol Effect Cairinurity study

coiimiity Kducation and Aïcohol Survey Haterna1 Questionnaire

1. Student Identification

2 . Student first name

3. 1s a Natural child Foster child Adopted

IF Foster or Adopted how long has she/he been in th i s home? Years Months Do you know whether alcohol was one of the reasons for placement? Yes No Have you ever been told that she/he might have Fetal alcohol Syndrome or Fetal Alcohol Effects? Yes No D o e s he/she originally come from this community

or from another community? (specify)

4. How many years of school did you finish yourself?

5. In the past 12 months, have there been any major stresses in your household such as divorce, separation, household move, house fire, deaths of a close relative etc, which might have affected your childrents school performance? If yes, please specify

6, What is the main source of income in your house? Salaries from work Unemployment insurance Social assistance or welfare

7 . Hou many people usually live in your house? -- 8. How many children live in your house (including grandchileen and children of friends or relatives)?

9 . Hou many bedrooms do you have?

10. How much schooling does the head of the household have? - - (years)

11. If father or mother are employed please give the occupation of each.

Occupation of father occupation of mother

N o t e to the interviever IF this is a foster or adopteà child, the interview ends here and the parents are assisted in filling out the CBCL. Efowever, in soie circu~stances, uhere the natural 10th- is no longer available and the foster or adoptive parent is a relative of the naturaï mther, the remainder of the questions may be answred by the foster/adoptive wther.

Thinking back to the time when you were pregnant w i t h

a. HOW

b. Did

c. Did d. How

many liveborn children did you have before -

you have any miscarriages before ? O 1 2 3 4 5 or more

you have any problem getting pregnant? Yes No m u c h weight did you gain during the pregnancy?

-- e. Did you have any serious accidents while pregnant? No- f. Did you take any prescribed drugs while pregnant? Yes- No-

IF YES, specify g. During which month did you first feel the baby move? h. Was delivered early? On time? Late? i. Did you smoke while you were pregnant? Yes No

IF YES, How many cigarettes per day? j. Did you drink any alcohol? Yes No

When? IF YES

About how many drinks per week on average (Including ber, wine and liquor)

At that tirne, about how many drinks could you hold without falling asleep or passing out?

Did close friends or relatives ever worry or conplain about your drinking during the time you were pregnant? Y e s No

Did you sometimes take a drink i n the morning when you first got up? Y e s NO

Did friends or family ever tell you about things you did or said when drinking that you could not remember? Yes No-

Did you ever think that you needed to cut doun on your drinking during the tirne you were pregnant? Y e s No

km Did you take any of the following drugs while you were pregnant?

marijuana Yes No LSD or acid Y e s No Cocaine Y e s NO- Talwin and Ritallin (T+Rgs) Y e s No Other street drugs Y e s No specif y How much?

When?

1. Did you sniff while pregnant with ? IF YES, what? When? How often?

What hospital was born in?

m. When was born did $/ne? Breath right away Y ~ S NO

Cry right away es NO Need Oxygen es NO Did you have a caesarian section or a vaginal

birth ? Did s/he corne head first? Yes No Was S/he a twin or triplet? Yes No Did s/he have any major problems after birth (eg

breathing problems, seizures, jaundice, feeding -

difficulties) Yes No IF YES specify

Did you breast feed ? Yes No If yes, how many months? -

Was diff icult to feed? Yes No Did have colic? Yes No

Were any malformations noted a t birth Yes N o IF YES specify

H o w many liveborn babies have you had since ?

r. H o w many stillborn babies have you had? se How many miscarriages have you had since ?

O 1 2 3 4 5 or more t. Have any of your chilâren (Live or stillborn) had any birth defects? IF YES, specify u. H a v e any of your brothers or sisters had children who were stillborn? Yes No v. H a v e any of your brothers or sisters had children with birth defects? Yes No IF YES, specify type

W. Do any of your brothers or sisters have children who have developmental delay or mental retardation Yes No IF YES, please specify who and what type

x . Do you have any brothers or sisters who have mental retardation? Yes No . IF YES, do you know the cause?

y. On the natural fatheros side are there any children with mental retardation among his brothers and sisters? Yes No IF YES, specify and if cause is known specify

2. Does the natural father have any nephews or nieces who

1 26

have mental retardation or developmental delay? Yes No

aa. Are you and the childrs father related as cousins (blood relatives)? Yes No

Now 1 am goinq t o ask you to answer a questionnaire about your child's behaviour. It will take about half an hour and 1 vil1 help you understand the questions if you need assistance. This questionnaire is used al1 over the world and if gives a very good idea of hou a child is behaving in cornparison to other children of the same aqe.

Appendix C. Hospital Records Review Fom used to collect data from each child's hospital records at their hospital of birth.

FAS Communiîy Saidy Hospitrl Recods R- Fom

Nuning üatabase: Date of Compîelian (1 1) Was alcohol used in pregnancy ? (O=no, 1 =yes)

When (trimester)? 1st 2nd 3rd All Frequency? Binge Occasional HeaVY Quantitatnre and Q u a l i i Infbrmation :

(1 2) Did the moaier smoke cigarettes during pregnancy? (Olno, l=yes) When (trimester)? 1st 2nd 3rd Al1 - How much (ügamtb per day)? Quantitative and Qualiitive Information:

- - - - - - - -

(1 3) Were drugs used R pregnancy ? (O=no,l =yes) Quantitative and Qualiitive Information :

-- - - - -

ûtbr Chart Revkw: (14) Nurshg Notes (re alcahol or drugs):

(1 5) Phyçician Comments (re alcohol or drugs) :

. - - -

(16) Social Work Notes (re alcohol or d m ) :

Appendix D. Physical Examination fom used during the Dysmorphology Assessment aspect of the Community FAS study.

ID #: DOB EXAM DATE :

Head- - 4. Shap : (O = Normal, 1 = Abnormal) 5. Whorl : (0,1,2,3 = Abnomul) 6. Eye Size : ( O = Nomual, 1 = Abnomul) 7. ICD : ( % 1 8. OCD: ( '5 9. Epicanthus : (O = No, 1 = Yes) 10. Sbrbismus : (O = No, 1 = Yes) 11. Ptosis : (O = No, 1 = Yes) Palpebrai Fissures:

12. Slant : (O=Horitontal, l=Up, BDown)

15. Philbum l e m : ( SI 10. Cupids bow : (OINormaI, I=Abnormal) 17.Upper lip: (û=Nom#l, 1=Thin, 24Ieft) 18. Patate: (OtNomul, 1=High Arched, 24ef t ) 19. MiMace: (OcNomiiil. l=Abnonnd) 20. Nose: (O=Normd, I=$hort, ZoUptumed,

jgkt Naocil fkiâge, 4=0thec)

24. Fingers: (û=Nomirl, l=Abnoniul) 25. CIinod.ctyly: (û= No, 1= Yes) 26. Brachydactyly: (Oe No, 1= Y=) n. oistaï Hypoplasia : (03 NO, I= Y-) 28. Polydactyiy: (O=No, l=Yem) 29.ûemaWgIyphics : (0INonnil, 1= AkKnnul) 30. Single Cmse: (@No, 1=Yfm) 31. Distal Tdradii: (03N0, 1= Yes) 32.Other Hand Anomalies: (@No, l=Yes) 33. Joints: (OINormal, 13Con(mtum) 34. PaIm Length: ( % 35. Hnd Length: ( % Mer-- 36. Neck: 37. Haidine: 38. Chest ! back: 39. Scoliosis: 40. Pectlm: 41. Heart Anom.: 42. Heart M u m c 43. Skin: 44. Hemangioma: 45. Hirsute: 46.Other Anomalies:

DX: (CkNomul. l=Dy.morphic, *FASI 3=Paftial FAS)

Appendix E. Normal Native cuwes (Figures 6 - 24) and their corresponding data tables (Tables 21 -39 ).

Figure 6. Normal Native Male Height Curve, derived from data colledeci on 74 Normal males (ages 5 - 15). The Shaded area represents the Caucasian standard graph for height (Hall et al, 1989).

Normal HeigM Graph Males

Figure 7. Normal Native Female Height Curve, derived from data collecteci on 59 Normal females (ages 5 -1 5). The Shaded area represents the Caucasian standard graph for height (Hall et al, 1989).

-2 WI. +16Wk +mwk -84 %île +mw+e -5 W k (C) + w nik (C)

Figure 8. Normal Native Male Weight Curve, derived from data colleded on 74 Normal males (ages 5 - 15). The Shaded area represents the Caucasian standard graph for weigM (Referenœ).

Normal Weight Gmph Males

- -

4 - 2 Wle + $6 %le +m Wle *W%Ue +m%ita -6We (C) +as W b (C)

Figure 9. Normal Native Fernale Weight Curve, deriveci from data collected on 59 Normal fernales (ages 5 -1 5). The Shaded area represents the Caucasian standard graph for weight (Referma).

Nomal Weight Gmph Females

Figure 10. Normal Native Male Head Circumference Curve, derived from data collecteci on 74 Nonnal males (ages 5 - 15). The Shaded area represents the Caucasian standard graph for head circumference (Nellhaus, 1968).

Normal Head Circumferenœ Graph Males

Figure 11. Normal Native Fernale Head Circumferenœ Cuve, derived from data wllected on 59 Normal females (ages 5 -15). The Shaded area represents the Caucasian standard graph for head circumference (Nellhaus, 1968)

Nomal Head Cirwmfbmncs Gnph Fernales

Figure 12. Normal Native Male Palpebral Fissure Length Curve, derived from data collected on 74 Normal males (age 5 - 15). The Shaded area represents the Caucasian standard graph for palpebral fissure length (pooled sex data) (Thomas et al, 1987).

Normal Palpebrial Fissure Length Gmph Males

Figure 13. Normal Native Female Palpebral Fissure Length Curve, derived from data colleded on 59 Nonnal fernales (age 5 - 15). The Shaded area represents the Caucasian standard graph for palpebral fissure length (pooled sex data) (Thomas et al, 1987).

Figure 14. Normal Native Male Philtrum Lengh Curve, derived from data collected on 74 Normal males (age 5 - 15). The Shaded area represents the Caucasian standard graph for philtrum length (pooled sex data) (Feingold and Bossert, 1 974).

Normal P h i h m bngth Gmph Males

-2 Wle 4 1 6 W k +m W h -81jCik

+m W k -3 W k (C) -00 W k (C) +or W h (C)

Figure 15. Normal Native Fernale Philtrum Length Curve, derived from data wllected on 59 Normal females (age 5 - 15). The Shaded area represents the Caucasian standard graph for philtnm length (pooled sex data) (Feingold and Bossert. 1974).

Notmal Philbum Length Gmph kal les

Figure 16. Normal Native Male lnner Canthal Distance Curve, derived from data collected on 74 Normal males (age 5 - 15). The Shaded area represents the Caucasian standard graph for inner canthal distance (pooled sex data) (Feingold and Bossert, 7 974).

Nomal lnner Canthal Distance Graph Males

Figure 17. Normal Native Female lnner Canthal Distance Curve, derived from data collecteci on 59 Normal females (age 5 - 15). The Shaded area represents the Caucasian standard graph for inner canthal distance (poded sex data) (Feingold and Bossert, 1974).

Normal lnner Canthal Distance Gmph Fernales

Figure 18. Nomial Native Male Outer Canthal Distance Curve, derived from data collecteci on 74 Normal males (age 5 - 15). The Shaded area represents the Caucasian standard graph for outer canthal distance (pooled sex data) (Feingold and Bossert, 1974).

Normal Outér Canthai Distance Gmph Males

Figure 19. Normal Native Fernale Outer Canthal Distance Cuwe, derived from data colleded on 59 N m a l females (age 5 - 15). The Shaded area represents the Caucasian standard graph for outer canthal distance (pooled sex data) (Feingold and Bossert, 1974).

Normal 0-r Canthal Distance Gmph Fernales

-2 %Ne -16Yiîe -ûô W k +84Wk *mwIe -3 W b (C) +Ql W h (C)

Figure 20. Normal Native Male Hand Length Curve, derived from data collecteci on 74 Normal males (age 5 - 15). The Shaded area represents the Caucasian standard graph for hand length (pooled sex data) (Feingold and Bossert, 1974).

Normal Hand Length Gmph Males

Figure 21. Normal Native Female Hand Length Cuwe, derived from data collected on 59 Normal females (age 5 - 15). The Shaûeâ area represents the Caucasian standard graph for hand length (pooled sex data) (Feingold and Bossert, 1974).

Nomal Hand Lmgth Gmph Females

Figure 22. Normal Native Male Palm Length Cuwe, deriveci from data collecteci on 74 Normal males (age 5 - 15). The Shaded area represents the Caucasian standard graph for palm length (pooled sex data) (Feingold and Bossert, 1974).

Normal Palm Length Gnph Males

Figure 23. Normal Native Fernale Palm Length Curve, derived from data collected on 59 Nomal females (age 5 - 15). The Shaded area represents the Caucasian standard graph for palm length (pooled sex data) (Feingold and Bossert, 1974).

Figure 24. Normal Native ON0 Angle Curve, defived from data collected on 133 Normal children (pooled sex data) (age 5 - 15). The Shaded area reptesents the Caucasian standard graph for ON0 angles (pooled sex data) (Hall et al,, 1989).

Nomal ON0 Angle Graph Males and ~emales

Com bined

Table 21 . Nonnal Male Height Data - m-

m Range (un) Mean Standard N (cm) Deviat ion

5 110-122 1 15.97 5-12 6

6 114.6 - 119.5 1 17.05 3-46 2

7 125.3 - 135.2 131 -35 3-97 8

8 124 - 141 129-38 5-55 9

9 130.4 - 148 1 39.68 7.1 3 8

10 131 - 153 144.63 6-4 10

11 142 - 155.4 147.39 3.99 10

12 146 - 164.5 156.3 5.63 10

13 156.2 - 165-1 160.28 3.83 4

Table 22. Normal Female Height Data.

Standard Deviation

1 16.21 3-96

Table 23- Normal Male WeigM Data

AW Range (kg) Mean (kg) Standard N Deviat ion

5 20-40 25-07 7.67 6

6 23-5 - 25.2 24.35 1 -20 2

7 27. 1 - 56.3 37.7 9-77 8

8 23-8 - 35-5 27.62 4.03 9

9 26-6 - S6.7 39-58 10.66 8

10 27-5 - 75.2 44-4 13.05 10

11 35.5 - 53 42-59 5.32 10

12 39 - 81 -5 54-79 14.85 10

13 44.1 - 65.6 55-38 9.92 4

14 52.3 - 87 74-62 12-51 6

Table 24. Normal Female Weight Data

A W Range (kg) Mean (kg) Standard N Deviation

5 17.8 - 25.2 21 -63 2.34 9

6 20 - 33.5 24.96 3.55 12

Table 25. Normal Male Head Circumferenœ Data

AW R ~ w Mean Standard N Deviation

L

Table 26. Normal Female Head Circurnferenœ Data. l

Age 1 Range 1 Mean 1 Standard 1 N 1 1 1 Deviation 1

Table 27. Normal Male Palpebral fissure Iength

Me Range Mean Standard N Deviation

5 2.5 - 2.8 2.62 0,133 6

6 2.5 2.5 O 2 1

Table 28. Normal Fernale Palpebral fissure length

A W Range Mean Standard N Deviation

5 2.5 - 2.7 2.52 0.067 9

6 2-3 - 2.6 2-49 0,067 12

Table 29. Normal Male lnner Canthal Distance

Range Mean Standard ûeviation

Table 30. Normal Female lnner Canthal Distance

Table 31. Normal Male Outer Canthal Distance

Table 32. Normal Female Outer Canthal Distanœ

Age Range Mean Standard N Deviation

Table 33- Normal Male Philtnm Length

&P Range Mean Standard N Deviation

5 1-4-2 1 -58 0.240 6

Table 34. Normal Fernale Philtrum Length

Age Range Mean Standard N Deviation

5 1 - 1.7 1 -41 0.247 9

Table 35. Normal Male Palm Length

Table 36. Normal Female Palm Length

Standard ûeviation

0-61 9

Age Range Mean Standard N Deviation

5 7 - 8.5 7.56 0.51 3 9

6 7.5 - 8.4 7-85 0.288 12

7 7.2 - 9.1 8.1 0.559 11

8 8 - 10.5 8.76 1 -00 5

9 8.3 - 10.1 9.27 0.907 3

10 8.2 - 10.5 9.28 0.973 5

11 8.8 - 10-5 9.88 0.81 O 4

12 9.5 - 10.2 9.8 0.361 3

13 9.5 - 10 9.83 0.236 4

Table 37. Nonnal Male Hand Length

&P Range Mean Standard ûeviation

5 11.7 - 13.8 12.78 0.91 5

6 12.5 - 13.2 12.85 0.495

7 13.5 - 16 14.66 0.807

Table 38. Nonnal Fernale Hand Length

Deviation

Table 39. Normal ON0 Angles (male and fernale combineci results)

&P MW Mean Standard N ûeviation

5 87- 103 94-53 4.84 15

6 85-98 91 .O? 3.20 14

7 85 - 105 92-47 4.96 19

8 81 -100 91 -64 4-86 14

9 m -97 90-36 3.88 11

10 87 - 96 89.93 2.91 15

11 83 - 94 90.21 3.79 14

12 82 - 94 88.1 5 3.48 13

13 78-98 90.81 6.22 8

14 82 - 93 87-88 4.09 8

15 90-98 . 94 5.66 2 -

Appendix F. Data used to compare the medians of the Caucasian curves versus the newly generated Native Curves.

HeigM - Males WeigM - Males Hed Citcumference (cm) 1 Males (cm)

Caucasian N a h Caucasian Native Caucasian Native

5 110 1 15.07 10 25.07 51 2 52.9

6 116 1 1 7.05 20.5 24.35 51.5 53.95

Me Height - Females Weight - Fernales Head Circumbrence (cm) Fernales (cm)

Caucasian Native Caucasian Native Caucasian Nabive

S 108.5 11611 18 21 -63 50.5 50.98

6 1 14.5 123.99 19.5 24.96 50-7 51 -46 I

M e Palpehl Fissure Lengü~ Qalpekal f i i r e Lem Phüaum Lem -Males (cm) -Fernales (cm) Males (cm)

Caucasian Native CauuWan Nalive Caucasbn N a m

5 2-63 2.62 2.63 2.52 1 -4 1.58

6 2.65 2.5 2.65 2.49 1 AS 1 .SS

7 2.67 2.7 2.67 2.55 1 .S 1.56

8 2.68 2.61 2-08 2.66 1 -55 1 .69

9 2.60 2-05 2.69 2.67 1.6 1.54

10 2-7 2.76 2-7 2.64 1 -65 1.42 1

11 2-71 2-79 2.71 2-7 1.65 1.59

&@ Ptrilbum Length - Fernales Hand Lem - Males Harid Cength - (cm) - (cm) Fernales (cm)

Caucasian N a h Caucasien Nathe Caucasian Native

Me Palm Length Palm Lemgth ON0 angle -Males (cm) - Fernales (cm) Males + Fernales

(degrees)

Caucasian Nalïue Caucasian Nalnre CauewPinn Nativ8

5 7.25 7.43 7.25 7.56 9s 94.53

6 7.5 7.4 7.5 7.85 94.5 91 .O7

7 7.8 8.1 8 7.8 8-1 94 92-47

8 8-1 822 8-1 8.76 93 91 -61

9 8.5 8-73 8.5 927 92 90.36

10 8.75 9.22 8.75 928 91.5 89.93

11 9.1 928 9.1 9.88 91 90.21

12 9.5 10.21 9.5 9.8

13 9-75 10 9-75 9.83 r

Me Inner Canthal DisCance lnner Canlhal DMance Outer Canthal Oistance Mele (cm) Fernale (cm) Male (cm)

Caucasian Nath Caucasian NatNe Caucasian Nalive

S 2.75 3-1 5 2.75 3.03 7-75 8.33

6 2.8 3.1 2.8 3.07 7.8 7.95

7 2.85 3.3 2-85 3.05 8.0 8.69

8 2.9 321 2.9 3.1 8 8.1 5 8.47

9 3.0 3.23 3.0 3A 8.îS 8.58

10 3.05 3.34 3.05 3.36 8.35 8.92

11 3.1 3-45 3.1 323 8.45 9.05

12 3.1 5 3.42 3.1 5 3.65 8.55 9.02

13 3.1 5 328 3.1 5 3-18 8.65 8.8

-

Fernale (cm) f

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