fetal and neonatal outcomes of diabetic.25

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Fetal and Neonatal Outcomes of DiabeticPregnancies

Joanne Yang, BSc, Elizabeth A. Cummings, MD, Colleen OConnell, PhD, and Krista Jangaard, MD

OBJECTIVE: To estimate whether the incidences of ad-

verse fetal and neonatal outcomes in infants of motherswith preexisting types 1 and 2 diabetes 1) differ frominfants of nondiabetic mothers in Nova Scotia (NS); and2) have changed between 1988 and 2002.

METHODS: Population-based cohort study using the NSAtlee Perinatal Database, a well-validated source of stan-dardized clinical information.

RESULTS: A total of 516 infants of diabetic mothers and150,589 infants of nondiabetic mothers from singletonpregnancies were studied. Infants of diabetic mothershad significantly higher rates of perinatal mortality (17.4/1,000 compared with 5.9/1,000, relative risk [RR] 3.01,95% confidence interval [CI] 1.555.84), major congenitalanomaly (9.1% compared with 3.1%, RR 2.97, 95% CI2.253.90), and large for gestational age birth (LGA, morethan 90th percentile weight for gestational age) (45.2%compared with 12.6%, RR 3.59, 95% CI 3.263.95) thaninfants of nondiabetic mothers. In infants of diabeticmothers, there was no improvement in perinatal mortal-ity (23.4/1,000 in 19881995 compared with 11.5/1000 in

19962002, P .340), incidence of LGA (48.0% in 19881995 compared with 42.3% in 1996 2002, P .237), orrate of major congenital anomaly (8.2% in 1988 1995compared with 10.0% in 19962002, P .560). Diabetesremained an independent risk factor for LGA infants andmajor congenital anomaly after adjusting for possibleconfounders.

CONCLUSION: Rates of adverse neonatal outcomes are39 times greater in infants of diabetic mothers com-

pared with those of nondiabetic mothers. There were nosignificant improvements in rates of perinatal mortality,congenital anomaly, or LGA birth in infants of diabeticmothers in 19962002 compared with 198895.(Obstet Gynecol 2006;108:64450)

LEVEL OF EVIDENCE: II-2

T

he presence of diabetes before pregnancy is well

known to be a risk factor for adverse neonataloutcomes, including increased rates of perinatal mor-tality, congenital anomaly, and macrosomia.1 In 1989,the St. Vincent Declaration in Europe made it ahealthcare goal to improve outcomes of diabeticpregnancies such that the incidence of adverse out-comes approached those of the general population.2

Since 1989, care of diabetes in general and duringpregnancy has changed; however, population-basedstudies show that the goals of the St. Vincent Decla-ration have not been reached.314 However, in se-lected populations with intensive diabetes manage-

ment before conception and during pregnancy, suchas participants in the Diabetes Control and Compli-cations Trial (1996), rates of spontaneous abortionand congenital malformation have approached ratesin the nondiabetic population.15 Because good glyce-mic control is necessary in the very early stages ofpregnancy to reduce the incidence of congenitalanomalies, prepregnancy counseling has been foundto improve outcomes significantly.16 However, withthe exception of some reports from Scandinavia thatdid not find a significant increase in death rates ofinfants born to diabetic women,17,18 most population-

based studies of nonselected diabetic mothers haveshown little improvement in pregnancy outcomes.314

The published population-based data regarding out-come of diabetic pregnancy varies among reportingcenters in Europe, and no population-based NorthAmerican data are available.

We report here the results of a large population-based study of diabetic pregnancy outcomes based onNorth American data. The objectives of this cohort

From the Department of Pediatrics, Izaak Walton Killam Health Centre andDalhousie University, Halifax, Nova Scotia, Canada.

The authors thank the Dalhousie University Faculty of Medicine ResearchCommittee Summer Studentship Program and Izaak Walton Killam SummerStudent Research Program for providing funding for this project, and theReproductive Care Program of Nova Scotia for providing access to data from theNova Scotia Atlee Perinatal Database.

Corresponding author: Elizabeth A. Cummings, Department of Pediatrics, IWKHealth Centre, 5850/5980 University Ave, Halifax, NS Canada B3K 6R8;e-mail: [email protected].

2006 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.ISSN: 0029-7844/06

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study were to 1) compare rates of perinatal mortality,congenital malformations, and growth disturbancesbetween women with pregestational diabetes andnondiabetic women and 2) determine whether therewas a change in incidence of these adverse outcomesbetween 1988 and 2002 in infants of diabetic mothers.

MATERIALS AND METHODS

A population-based cohort study design was used tocompare pregnancy outcomes in all nondiabeticmothers and mothers with pregestational diabetes inNova Scotia, Canada delivering between January 1,1988 and December 31, 2002. Outcomes in infants ofdiabetic mothers were examined in two epochs, 1988to 1995, and 1996 to 2002, to determine whetherchanges in diabetic pregnancy management in NovaScotia instituted in the mid 1990s translated to changein pregnancy outcomes.

The population of Nova Scotia is approximately900,000 and is predominantly white, with only 4% of

the population being visible minorities.19 Births inNova Scotia take place in 11 maternity units through-out the province, with approximately one half occur-ring at the Izaak Walton Killam Health Centre inHalifax, the only tertiary care center in the province.The prevalence of diabetes in the Nova Scotia adultpopulation was estimated to be 4.06% in 1995, indi-cating there were approximately 36,540 diabetic pa-tients in the province in that year (LeBlanc J. Theprevalence of diabetes mellitus in Nova Scotia: whatcan we learn from routinely collected health data?Diabetes Care in Nova Scotia: a newsletter of the

Diabetes Care Program of Nova Scotia. 1998;8:13).Changes in the organization of care of diabetes inpregnancy occurred in the mid 1990s including theestablishment of a multidisciplinary pregnancy anddiabetes clinic and the establishment of local guide-lines. In addition, general diabetes care was changingafter publication of the results of the Diabetes Controland Complications Trial in 1993.20 The Pregnancyand Diabetes Education Centre at the Izaak WaltonKillam Health Centre opened in 1995 and currentlyfollows approximately 40 pregnancies per year inwomen with preexisting diabetes from throughout the

province. Most women are not referred to the clinicuntil several weeks into the pregnancy and some arefully managed in their local centers. In 1993, theDiabetes Care Program of Nova Scotia, a provincialorganization that sets standards for diabetes care inthe province, published guidelines for management ofdiabetic pregnancy. These were disseminatedthroughout the province and an update was producedin 2000.21

Data were obtained from the Nova Scotia AtleePerinatal Database, which is located at the IzaakWalton Killam Health Centre and maintained andadministered by the Reproductive Care Program ofNova Scotia. Since 1988, the Nova Scotia AtleePerinatal Database has collected data on standardizedclinical forms used uniformly across the province.Information collected includes demographic vari-

ables, detailed clinical information on maternal med-ical conditions, labor and delivery events, and neona-tal outcomes for all pregnancies reaching 20 weeks ofgestation and 500 g at birth in Nova Scotia, Canada,and for most out of province deliveries among NovaScotia residents. It also includes follow-up informa-tion on death and cause of death in the first year oflife. Standardized data collection forms (which arealso used as clinical care tools) are used throughoutthe province. After discharge from hospital afterdelivery, data are abstracted from the medical recordsby health records personnel and entered in an Oracle

database (Oracle, Redwood Shores, CA). Data hasbeen shown to be reliable by validation studies.22 Anongoing data quality assurance program, which in-cludes periodic abstraction studies, shows that theinformation in the database is reliable.

Maternal and fetal characteristics extracted fromthe database include age, parity, diabetes by Whitesclassification,23 prepregnancy weight and weight gainduring pregnancy, smoking status at first perinatalvisit, chronic and pregnancy-induced hypertension(includes preeclampsia), gestational age and weight atbirth, and method of delivery. Diabetes status was

abstracted from the standardized antenatal recordcompleted at the first antenatal visit and thus docu-mented as present before pregnancy (Whites classesB, C, D, F, and R). Thus, women with insulin-dependent diabetes mellitus, noninsulin-dependentdiabetes mellitus requiring insulin before pregnancy,and noninsulin-dependent diabetes mellitus not re-quiring insulin before pregnancy were included. Preg-nancies complicated by gestational diabetes (Whitesclass A) were excluded from the analysis (n4,067).Infants whose gestational ages or birth weights wereunknown were excluded from the analysis. Only

singleton pregnancies were included.The primary neonatal outcomes of interest were

perinatal mortality, major congenital anomalies, mac-rosomia, and fetal growth restriction. Perinatal mor-tality was defined as death between 20 weeks ofgestation and day 7 after birth.24 Stillbirth was definedas death between 20 weeks of gestation and beforebirth.24 Infant mortality was defined as death afterbirth and before 1 year of age, these data being

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available for the population studied.24 Major congen-ital anomaly was defined in the database as one whichis any of the following: lethal, life-shortening, life-threatening, requires major surgery, or affecting in asignificant way the quality of life. Chromosomalabnormalities are included in this definition. Macro-somia was defined as birthweight more than the 90thpercentile (large for gestational age, LGA) and fetal

growth restriction as birthweight less than the 10thpercentile (small for gestational age, SGA) for Cana-dian infants.25 Ethics approval (#3012) for the studywas obtained from the Research Ethics Boards of theIzaak Walton Killam Health Centre and DalhousieUniversity, both in Halifax, Nova Scotia.

Data were analyzed using descriptive statistics asmeansstandard deviations unless otherwise speci-fied. Continuous variables were analyzed using Stu-dent t test, and categorical variables by means of 2

analysis, or Fisher exact test when appropriate. Rela-tive risk (RR) with 95% confidence intervals (CIs) and

attributable risk were calculated using standard meth-ods. Pvalues less than .05 were considered significant.Outcomes reaching statistical significance on univari-able analysis were entered into a backward condi-tional regression to obtain adjusted RR. For thestatistical analysis, SPSS for Windows 11.5 (SPSS Inc.,Chicago, IL) was used.

RESULTS

There were 516 singleton infants of mothers withpreexisting diabetes and 150,589 singleton infants ofnondiabetic mothers born between January 1988 and

December 2002. Characteristics of mothers and new-

borns are shown in Table 1. Women with preexistingdiabetes were on average older and heavier at concep-tion, and more likely to have chronic and pregnancy-induced hypertension compared with nondiabeticmothers. The majority of women had diabetes of WhitesClass B (53.7%) or C (31.4%). Fewer women haddiabetes of Whites class D (10.7%), F (1.2%), or R (3.1%).

Of the 516 diabetic pregnancies, there were 13

(2.5%) deaths in total. Five of the infants were still-born. Four deaths occurred between birth and 7 daysof age, three between 7 and 28 days, and one between28 days and 1 year of age (Table 2). Major congenitalanomaly was stated as the cause of five of the deaths(38.5%) among infants of diabetic mothers: one in theperinatal period, and the remainder by 1 year of age.

Perinatal mortality and infant mortality rates forinfants of diabetic mothers were significantly higherthan in the nondiabetic population (Table 3). Afterthe rate of perinatal mortality was adjusted for majorcongenital anomaly, preterm birth, and preexisting

maternal hypertension, maternal diabetes was not astatistically significant contributor to perinatal mortal-ity (P.760). The rate of premature birth (defined asbirth before 37 weeks gestation) was significantlyhigher in infants of diabetic mothers, with most ofthese being near-term births (between 34 and 36weeks) (Table 1).

There were 47 infants (9.1%) with one or moremajor congenital anomaly (Table 4). Of these, themajority of anomalies were cardiac. The most com-mon cardiac anomaly was ventricular septal defect.Musculoskeletal, central nervous system, and ear,

nose, and throat anomalies, as well as hypospadias

Table 1. Characteristics of Diabetic and Nondiabetic Women and Their Infants in Nova Scotia, 19882002

Characteristic

Diabetes(516 Infants

and Mothers)

Nondiabetes(150,589 Infants

and Mothers)

DiabetesCompared With

Nondiabetes P

Maternal age (y) 29.28 (5.10) 27.83 (5.40) .001Nulliparous 235 (45.5) 66,934 (45.5) 1.02 (0.931.13) .650Chronic hypertension 32 (6.2) 1,312 (0.9) 7.12 (5.0710.00) .001Pregnancy induced hypertension 142 (27.5) 13,645 (9.1) 3.04 (2.643.50) .001

Prepregnancy weight (kg) 73.95 (

19.07) 65.30 (

14.46)

.001Weight gain during pregnancy (kg) 14.11 (7.26) 14.59 (6.14) .180Maternal smoking 137 (27.3) 42,318 (29.0) 0.94 (0.821.09) .440Gestational age (wk) 37.29 (2.11) 39.35 (1.92) .001Preterm birth 143 (27.7) 7909 (5.2) 5.28 (4.586.08) .001Birth weight (g) 3,534.60 (749.84) 3,461.56 (580.81) .030Small for gestational age 26 (5.0) 15,140 (10.0) 0.50 (0.340.73) .001Large for gestational age 233 (45.2) 18,932 (12.6) 3.59 (3.263.95) .001Adjusted large for gestational age* 5.36 (4.376.56) .001

Data are mean (standard deviation), n (%), or relative risk (95% confidence interval) unless otherwise specified.* Large for gestational age was adjusted for prepregnancy weight and weight gain during pregnancy and expressed as an odds ratio.

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24.6 to 48.0 per thousand reported in other popula-tion-based studies published in the last 10 years.5,6

The RR of death in the perinatal period in NovaScotia infants of diabetic mothers is also at the lowerend of the range of 2.55.4 previously reported. Thereasons for this are unclear; most previous studies arefrom Scandinavia, the United Kingdom, or Western

Europe, where there is access to a similar system ofsocialized medicine; however, it is possible that theethnic homogeneity of the Nova Scotia population isa factor. The only study reporting a lower RR at 2.5included only infants of mothers with noninsulin-dependent diabetes mellitus and may thus reflect aless severely affected population.6 After adjusting formajor congenital anomaly, maternal hypertension,and preterm birth, maternal diabetes was no longer a

significant factor in perinatal mortality. This suggeststhat these three factors are important contributors tothe excess mortality in infants of diabetic mothers andmust be targeted to reduce perinatal mortality. Con-genital anomalies are known to be related to poormaternal glycemic control in the early weeks ofpregnancy, the period of organogenesis.26 Therefore,

if improvements in congenital anomaly rates are tooccur, efforts to ensure that women are referred tospecialized diabetes in pregnancy clinics for precon-ceptional counseling and early pregnancy care mustbe targeted.16 In our center, most women are referredto the clinic when they are already several weeks intotheir pregnancy. For these women, targeting tightglycemic control and management of hypertensionduring the child bearing years is important. Further

Table 4. Major Congenital Anomalies in Infants Born of Mothers With and Without Diabetes, 19882002

Type of Congenital AnomalyIDM

(n 516)Non-IDM

(n 150,589)IDM Compared With

non-IDM P

Total 47 (9.1) 4,625 (3.1) 2.97 (2.253.90) .001Adjusted total* 3.10 (2.284.22)* .001Cardiac 25 (4.8) 1,147 (0.8) 6.36 (4.329.36) .001

Dextrocardia 2 (0.4) 31 (0.0) 18.83 (4.5278.47) .010

Patent ductus arteriosis 4 (0.8) 135 (0.1) 8.65 (3.2123.29) .010Ventricular septal defect 10 (1.9) 511 (0.3) 5.71 (3.0710.61) .001

Musculoskeletal 14 (2.7) 1,609 (1.1) 2.54 (1.514.27) .001Caudal regression 3 (0.6) 4 (0.0) 218.88 (49.11975.55) .001

Central nervous system 7 (1.4) 275 (0.2) 7.43 (3.5415.65) .001Spina bifida 1 (0.2) 17 (0.0) 17.17 (2.29128.76) .060

Ear, nose, and throat 5 (1.0) 368 (0.2) 3.97 (1.659.54) .010Genitourinary 3 (0.6) 659 (0.4) 1.33 (0.434.12) .500

Hypospadias complex 6 (1.2) 626 (0.4) 2.80 (1.266.22) .020

IDM, infants born of mothers with diabetes mellitus.Data are n (%) or relative risk (95% confidence interval) unless otherwise specified.* Major congenital anomaly was adjusted for maternal smoking and age and expressed as an odds ratio.

Table 5. Comparison of Rates of Major Outcomes in Two Eras, 19881995 compared with 19962002 inInfants of Diabetic and Nondiabetic Mothers

19881995* 19962002

19981995Compared With

19962002 P

Perinatal mortalityIDM 23.4/1,000 (6) 11.5/1,000 (3) 2.03 (0.518.03) .340Non-IDM 6.6/1,000 (586) 4.8/1,000 (297) 1.38 (1.201.59) .001

Major congenital anomalyIDM 8.2 (21) 10.0 (26) 0.82 (0.471.42) .560Non-IDM 3.0 (2,687) 3.1 (1,938) 0.97 (0.921.03) .350

Large for gestational ageIDM 48.0 (123) 42.3 (110) 1.14 (0.951.37) .237Non-IDM 11.2 (9,891) 14.6 (9,041) 0.77 (0.750.79) .001

IDM, infants born of mothers with diabetes mellitus.Data are n/1,000 (n), % (n), or relative risk (95% confidence interval).* n256 IDM and 88,510 non-IDM n260 IDM and 62,079 non-IDM

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study to determine factors associated with pretermbirth in women with diabetes is warranted.

The rate of congenital anomaly in infants ofdiabetic mothers in Nova Scotia at 91 per 1,000 issimilar to many recently reported population-basedstudies that range from 83 to 99 per 1,000.3,57,10

However, two reports from Scandinavia9,13 and onefrom Scotland4 including only infants of women with

insulin-dependent diabetes mellitus, have foundlower rates of anomalies, ranging from 39 to 60 per1,000. This wide variation in congenital anomaly ratesmay be due in part to differing definitions of majorcongenital anomaly and to differences in detectionand pregnancy termination rates. Because we did nothave access to data concerning pregnancies resultingin termination or pregnancies ending before 20 weeksof gestation or before the infant weight had reached500 g, it is likely that our study underestimates therates of congenital anomaly in our population, espe-cially in the more recent years when improved detec-

tion methods may have led to a greater number ofearly terminations. These data were available in someother population-based studies, even those reportinglower anomaly rates.4,13 Therefore, our population hasa relatively high rate of congenital anomaly comparedwith other recent reports, and the reasons for thismust be sought.

We report a very high rate of LGA infants atalmost one half (45.2%) of all births to diabeticwomen. It is difficult to compare our numbers withthose of studies including only women with insulin-dependent diabetes mellitus who are more likely to

have low birth weight babies; however, this rate ofLGA is high even compared with the 28% found byDunne et al6 in women with noninsulin-dependentdiabetes mellitus, but similar to a recent report fromScotland.4 Infants of diabetic mothers in our popula-tion also had higher rates of complications associatedwith LGA, including shoulder dystocia, fractures, andbrachial plexus injury compared with other infants.The rate of cesarean delivery in our population ofdiabetic women was also high at 49.0%; however, wefound that nonmacrosomic infants were just as likelyas macrosomic infants to be born by cesarean birth

(P.251).Despite improvements in the organization of

management of diabetic pregnancy care in NovaScotia, this population-based study revealed trendstoward, but statistically insignificant improvements inperinatal mortality and LGA rates for infants ofdiabetic mothers between 1988 and 2002 and nochange in rates of congenital anomalies. The reasonfor the lack of improvement is unclear. The popula-

tion of women with diabetes experiencing pregnancymay have changed during this time, because there hasbeen an increase in obesity in pregnancy,27 perhapsleading to more noninsulin-dependent diabetes mel-litus among the latter group. It is also possible that thenumber of deaths was too small to show a statisticallysignificant difference in mortality over time, becausethere were only nine perinatal deaths among infants

of diabetic mothers in the entire 15-year period.During this same period, perinatal mortality ratesdecreased significantly in nondiabetic women.

The strengths of this study include the largenumber of births, the population-based design, withthe availability of complete data regarding outcomeson all births to women with and without diabetes inthe same period, and the high quality of the data inthe Nova Scotia Atlee Perinatal Database. The qualityof the Nova Scotia Atlee Perinatal Database wasdemonstrated when it was used to validate stillbirthand live birth infant death files by Statistics Canada.22

In this validation study, data from Statistics Canadawere shown to be 92% to 99% complete for stillbirthsand infant deaths respectively when evaluated againstthe Nova Scotia Atlee Perinatal Database. Our cur-rent study has a few limitations. The data availabledid not allow differentiation between type 1 and type2 diabetes, but because diabetes was classified usingWhites Classification, gestational diabetes was easilyexcluded. Clinical information regarding glycemiccontrol and attendance at a specialized diabetes clinicduring pregnancy was not available. Finally, thedatabase does not contain information regarding ter-

minations or pregnancy losses before 20 weeks gesta-tion or 500 g fetal weight. Despite these limitations,this study does provide valuable information in that itrepresents one of only a few Canadian studies on thesubject, and is the first population-based study inNorth America to report neonatal outcomes in preg-nancies in women with type 1 and type 2 diabetes.

Putting the findings of this study together, we seea very high rate of LGA, preterm birth, and cesareandelivery, and a relatively high rate of congenitalanomalies compared with other reports of outcomesof diabetic pregnancy. All of these outcomes may be

related to suboptimal glycemic control during preg-nancy. The study spans a period of change in theorganization of diabetes care, and it was hypothesizedthat outcomes would improve over time. We, how-ever, failed to demonstrate a significant improvementin the major outcomes studied. This points out theimportance of reliably documenting outcomes of di-abetic pregnancy in populations and avoiding theassumption that changes in care will automatically

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translate into changes in outcomes. Careful examina-tion of maternal hemoglobin A1c (preconception andduring pregnancy) and attendance or nonattendanceat the diabetes and pregnancy clinic is an essentialnext step in understanding the reasons for the persis-tence of increased rates of adverse outcomes of dia-betic pregnancy in Nova Scotia.

REFERENCES1. Walkinshaw SA. Pregnancy in women with pre-existing dia-

betes: management issues. Semin Fetal Neonatal Med 2005;10:30715.

2. Diabetes care and research in Europe: the Saint Vincentdeclaration. Diabet Med 1990;7:360.

3. Platt MJ, Stanisstreet M, Casson IF, Howard CV, WalkinshawS, Pennycook S, et al. St. Vincents Declaration 10 years on:outcomes of diabetic pregnancies. Diabet Med 2002;19:21620.

4. Penney GC, Mair G, Pearson, DW, Scottish Diabetes inPregnancy Group. Outcomes of pregnancies in women withtype 1 diabetes in Scotland: a national population-based study.BJOG 2003;110:31518.

5. Hawthorne G, Robson S, Ryall EA, Sen D, Roberts SH, WardPlatt MP. Prospective population based study of outcome ofpregnancy in diabetic women: results of the Northern DiabeticPregnancy Audit, 1994. BMJ 1997;315:27981.

6. Dunne F, Brydon P, Smith K, Gee H. Pregnancy in womenwith Type 2 diabetes: 12 years outcome data 1990 2002.Diabet Med 2003;20:7438.

7. Casson IF, Clarke CA, Howard CV, McKendrick O, Penny-cook S, Pharoah PO, et al. Outcomes of pregnancy in insulindependent diabetic women: results of a five year populationcohort study. BMJ 1997;315:2758.

8. Vaarasmaki MS, Hartikainen A, Anttila M, Pramila S, KoivistoM. Factors predicting peri- and neonatal outcome in diabeticpregnancy. Early Hum Dev 2000;59:6170.

9. Nielsen GL, Nielsen PH. Outcome of 328 pregnancies in 205

women with insulin-dependent diabetes mellitus in the countyof Northern Jutland from 1976 to 1990. Eur J Obstet GynecolReprod Biol 1993;50:338.

10. Evers IM, de Valk, HW, Visser GH. Risk of complications ofpregnancy in women with type 1 diabetes: nationwide pro-spective study in the Netherlands. BMJ 2004;328:915.

11. Sharpe PB, Chan A, Haan EA, Hiller JE. Maternal diabetesand congenital anomalies in South Australia 1986 2000: apopulation-based cohort study. Birth Defects Res A Clin MolTeratol 2005;73:60511.

12. von Kries R, Kimmerle R, Schmidt JE, Hachmeister A, BohmO, Wolf HG. Pregnancy outcomes in mothers with pregesta-tional diabetes: a population-based study in North Rhine(Germany) from 1988 to 1993. Eur J Pediatr 1997;156:9637.

13. Jensen DM, Damm P, Moelsted-Pedersen L, Ovesen P, West-ergaard JG, Moeller M, et al. Outcomes in type 1 diabeticpregnancies: a nationwide, population-based study. DiabetesCare 2004;27:281923.

14. Silva Idos S, Higgins C, Swerdlow AJ, Laing SP, Slater SD,Pearson DW, et al. Birthweight and other pregnancy outcomesin a cohort of women with pre-gestational insulin-treateddiabetes mellitus, Scotland, 1979 95. Diabet Med 2005;22:4407.

15. Pregnancy outcomes in the Diabetes Control and Complica-tions Trial. Am J Obstet Gynecol 1996;174:134353.

16. McElvy SS, Miodovnik M, Rosenn B, Khoury JC, Siddiqi T,Dignan PS, et al. A focused preconceptional and early preg-nancy program in women with type 1 diabetes reduces peri-

natal mortality and malformation rates to general populationlevels. J Matern Fetal Med 2000;9:1420.

17. Cnattingius S, Berne C, Nordstrom ML. Pregnancy outcomeand infant mortality in diabetic patients in Sweden. DiabetMed 1994;11:696700.

18. Nordstrom L, Spetz E, Wallstrom K, Walinder O. Metaboliccontrol and pregnancy outcome among women with insulin-dependent diabetes mellitus. A twelve-year follow-up in thecountry of Jamtland, Sweden. Acta Obstet Gynecol Scand1998;77:2849.

19. Statistics Canada. ProfileNova Scotia (2001). Available at: http://w w w 1 2 . s tatc an . c a/en g l i s h /p r of i l 0 1 /C P 0 1 /D etai l s /Page.cfm?LangE&Geo1PR&Code112&Geo2-Pr&Code201&DataCount&SearchTextNova%20Scotia&SearchTypeBegins&SearchPR01&B1All&GeoLevel&GeoCode12. Retrieved July 17, 2004.

20. The Diabetes Control and Complications Trial ResearchGroup. The effect of intensive treatment of diabetes on thedevelopment and progression of long-term complications ininsulin-dependent diabetes mellitus. The Diabetes Control andComplications Trial Research Group. N Engl J Med 1993;329:97786.

21. Diabetes Care Program of Nova Scotia. In: Dunbar M, Fegu-son L, editors. The pregnancy & diabetes management guide-lines. 1st ed. Halifax (Nova Scotia): Nova Scotia Department ofHealth; 1993.

22. Fair M,CyrM, Allen AC, Wen SW, Guyon G, MacDonald RC, etal. Validation study for a record linkage of births and infant deathsin Canada (Statistics Canada, Catalogue 84F0013XIE) 1999. Avail-

able at: http://www.statcan.ca/english/research/84F0013XIE/84F0013XIE1992001.pdf. Retrieved June 8, 2006.

23. White P. Classification of obstetric diabetes. Am J ObstetGynecol 1978;130:22830.

24. Statistics Canada. Health Indicators December 2000. Avail-able at: http://www.statcan.ca/english/freepub/82-221-XIE/defin.htm. Retrieved May 2, 2006.

25. Kramer MS, Platt RW, Wen SW, Joseph KS, Allen A, Abra-hamowicz M, et al. A new improved population-based Cana-dian reference for birth weight for gestational age. Pediatrics2001;108:E35.

26. Kitzmiller JL, Gavin LA, Gin GD, Jovanovic-Peterson L, MainEK, Zigrang WD. Preconception care of diabetes: glycemiccontrol prevents congenital anomalies. JAMA 1991;265:7316.

27. Robinson HE, OConnell CM, Joseph KS, McLeod NL.Maternal outcomes in pregnancies complicated by obesity.Obstet Gynecol 2005;106:135764.

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