the three types of biomedical research

46
Department of Epidemiology, Michigan State University NEW APPROACHES TO NEW APPROACHES TO STUDYING THE ORIGINS OF STUDYING THE ORIGINS OF CEREBRAL PALSY CEREBRAL PALSY Nigel Paneth MD MPH Nigel Paneth MD MPH Michigan State University Michigan State University http://www.epi.msu.edu/faculty/paneth.htm University of Wisconsin April 2, 2009

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Page 1: The three types of biomedical research

Department of Epidemiology, Michigan State University

NEW APPROACHES TO NEW APPROACHES TO STUDYING THE ORIGINS OF STUDYING THE ORIGINS OF

CEREBRAL PALSY CEREBRAL PALSY

Nigel Paneth MD MPHNigel Paneth MD MPHMichigan State UniversityMichigan State University

http://www.epi.msu.edu/faculty/paneth.htm

University of WisconsinApril 2, 2009

Page 2: The three types of biomedical research

Department of Epidemiology, Michigan State University

WHY STUDY CEREBRAL PALSY?WHY STUDY CEREBRAL PALSY?

CP is the commonest severe CP is the commonest severe neurodevelopmental disability in children, neurodevelopmental disability in children, with a prevalence of 1 per 500 school-age with a prevalence of 1 per 500 school-age children.children.

Lifetime direct costs for each annual CP Lifetime direct costs for each annual CP birth cohort are estimated at $11.5 B.birth cohort are estimated at $11.5 B.

CP prevalence has not declined since CP prevalence has not declined since population registries began counting in the population registries began counting in the 1950’s.1950’s.

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Department of Epidemiology, Michigan State University

AND YETAND YET

NIH has not a single funded R01 directly NIH has not a single funded R01 directly investigating the etiology of CP in humansinvestigating the etiology of CP in humans

The private foundation for CP research The private foundation for CP research (now called CP International) spends $1 M (now called CP International) spends $1 M per year on grants. By contrastper year on grants. By contrast– Cystic Fibrosis foundation - $100M per yearCystic Fibrosis foundation - $100M per year– Juvenile Diabetes foundation - $130 M per yearJuvenile Diabetes foundation - $130 M per year

Page 4: The three types of biomedical research

Department of Epidemiology, Michigan State University

Sigmund Freud was the leading European authorityon CP of the late 19th Century. He authored threeMonographs on CP in the 1890’s

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Department of Epidemiology, Michigan State University

William Osler wrote the only19th century monograph on CP published in the US

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Department of Epidemiology, Michigan State University

NEWEST DEFINITION NEWEST DEFINITION OF CEREBRAL PALSY OF CEREBRAL PALSY

““Cerebral palsy describes a group of disorders of Cerebral palsy describes a group of disorders of the development of movement and posture that the development of movement and posture that are attributed to non-progressive disturbances are attributed to non-progressive disturbances that occurred in the developing fetal or infant that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, often accompanied by disturbances of sensation, cognition, communication, perception and/or cognition, communication, perception and/or behavior, and/or by a seizure disorder.” behavior, and/or by a seizure disorder.”

Rosenbaum P et al: Dev Med Child Neurol 2005;47:572-4Rosenbaum P et al: Dev Med Child Neurol 2005;47:572-4

Page 7: The three types of biomedical research

Department of Epidemiology, Michigan State University

CP PREVALENCE IN 12 NATIONAL CP PREVALENCE IN 12 NATIONAL REGISTRIESREGISTRIES

1.63

2.021.94

2.02

1.87

2.08 2.08

2.33

2.23

2.12

1

1.2

1.4

1.6

1.8

2

2.2

2.4

1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000

CP/1,000

Linear(CP/1,000)

N of observations1950 - 1; 1955 - 3 1960 - 4; 1965 - 3 1970 - 6; 1975 - 51980 - 8; 1985 -141990 - 7; 1995 - 2

Page 8: The three types of biomedical research

Department of Epidemiology, Michigan State University

FIVE BIOLOGICAL PROCESSES THAT HAVE FIVE BIOLOGICAL PROCESSES THAT HAVE BEEN EXAMINED EPIDEMIOLOGICALLY BEEN EXAMINED EPIDEMIOLOGICALLY

IN RELATION TO CPIN RELATION TO CP

1.1. Birth asphyxiaBirth asphyxia

2.2. Infection/inflammationInfection/inflammation

3.3. Ventilatory factorsVentilatory factors

4.4. Thyroid hormonesThyroid hormones

5.5. Magnesium sulfate in labor Magnesium sulfate in labor

Page 9: The three types of biomedical research

Department of Epidemiology, Michigan State University

THE OLD CONSENSUS ON BIRTH THE OLD CONSENSUS ON BIRTH ASPHYXIAASPHYXIA

Birth asphyxia isBirth asphyxia is the the major cause major cause of cerebral palsy, and contributes of cerebral palsy, and contributes in an important way to mental in an important way to mental retardation and other cognitive retardation and other cognitive and developmental problems.and developmental problems.

Careful monitoring, detection and Careful monitoring, detection and treatment of asphyxia in labor will treatment of asphyxia in labor will substantially reduce the morbidity substantially reduce the morbidity burden from birth asphyxia.burden from birth asphyxia.

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Department of Epidemiology, Michigan State University

PROBLEMS WITH THE OLD CONSENSUSPROBLEMS WITH THE OLD CONSENSUS

1.1. Evidence linking measures or proxies of Evidence linking measures or proxies of birth asphyxia to CP is weak, except in birth asphyxia to CP is weak, except in rare and extreme cases.rare and extreme cases.

2.2. In spite of nearly universal electronic In spite of nearly universal electronic fetal monitoring in labor, and a fetal monitoring in labor, and a seven-seven-fold rise in the cesarean section ratefold rise in the cesarean section rate in in the US since 1970, there is no evidence the US since 1970, there is no evidence of a decline in the prevalence of CP.of a decline in the prevalence of CP.

3.3. Other factors have emerged as Other factors have emerged as significant in the background of children significant in the background of children with CPwith CP

Page 11: The three types of biomedical research

Department of Epidemiology, Michigan State University

THE NATIONAL COLLABORATIVE THE NATIONAL COLLABORATIVE PERINATAL PROJECTPERINATAL PROJECT

Enrollment 1959-1966 at 12 major Enrollment 1959-1966 at 12 major medical centersmedical centers

> 55,000 Pregnancies enrolled, and > > 55,000 Pregnancies enrolled, and > 45,000 children followed to age 7.45,000 children followed to age 7.

PURPOSE: to study the relationship of PURPOSE: to study the relationship of pregnancy and labor events to CP. pregnancy and labor events to CP.

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Department of Epidemiology, Michigan State University

APGAR SCORES AND CEREBRAL APGAR SCORES AND CEREBRAL PALSY IN INFANTS PALSY IN INFANTS >> 2,500 G 2,500 G

0.2 1.54.7

16.7

36

57.1

0

10

20

30

40

50

60

1 MIN 7-10

1 MIN0-3

5 MIN

0-3

10MIN0-3

15MIN0-3

20MIN0-3

% WITH CP

Which columnproduced the mostChildren with CP?

Page 13: The three types of biomedical research

Department of Epidemiology, Michigan State University

CP RISK IN RELATION TO OB CP RISK IN RELATION TO OB COMPLICATIONS IN BABIES > 2,500 GCOMPLICATIONS IN BABIES > 2,500 G

CP RISKCP RISK NO OBSTETRIC COMPLICATIONS (49%)NO OBSTETRIC COMPLICATIONS (49%) 0.3%0.3%

COMMON COMPLICATIONS COMMON COMPLICATIONS – NUCHAL CORD (18%)NUCHAL CORD (18%) 0.3%0.3%– MECONIUM (25%)MECONIUM (25%) 0.4%0.4%– 22NDND STAGE STAGE >> 1 HOUR (10%) 1 HOUR (10%) 0.3%0.3%– MID OR HIGH FORCEPS (8%)MID OR HIGH FORCEPS (8%) 0.4%0.4%

LESS COMMON COMPLICATIONSLESS COMMON COMPLICATIONS– CORD PROLAPSE CORD PROLAPSE 0.4%0.4%– PLACENTA PREVIAPLACENTA PREVIA 0.6%0.6%– BREECH POSITION BREECH POSITION 1. 0%1. 0%– ABRUPTIO PLACENTAEABRUPTIO PLACENTAE 1.9%1.9%

Page 14: The three types of biomedical research

Department of Epidemiology, Michigan State University

““ASPHYXIA” AND CP IN THE ASPHYXIA” AND CP IN THE NCPP STUDYNCPP STUDY

23 CHILDRENWITH OTHER REASONS FOR CP

12 < 2KG, 14 NON-CNS ANOM ALY1 M ICROCEPHALY, 7 PRENATAL RISK

17 CHILDREN"PURE" ASPHYXIAL DAM AGE

<10% OF ALL CP1 PER 2,700 BIRTHS

40 CHILDRENWITH ANY ASPHYXIA INDICATOR

149 CHILDRENWITH NO ASPHYXIA INDICATOR

189 CHILDRENWITH CP

45, 449CHILDREN

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INFECTION AND INFECTION AND INFLAMMATIONINFLAMMATION

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Department of Epidemiology, Michigan State University

META-ANALYSIS FINDINGSMETA-ANALYSIS FINDINGSFOR CHORIOAMNIONITIS AND CPFOR CHORIOAMNIONITIS AND CP

Preterm infants Preterm infants pooled OR = pooled OR = 1.91.9

Term infants Term infants pooled OR = 4.6pooled OR = 4.6

Wu et al Ment Retard Dev Disabil Res Rev. 2002;8:25-9.

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Department of Epidemiology, Michigan State University

CYTOKINESCYTOKINES

Several studies have shown associations Several studies have shown associations between cytokine levels and later CPbetween cytokine levels and later CP

The cytokines include The cytokines include IL-18,IL-6, IL-1β, IL-IL-18,IL-6, IL-1β, IL-8, TNF-α and metalloproteinase-88, TNF-α and metalloproteinase-8

The cytokines have been measured in The cytokines have been measured in cord cord blood, neonatal blood and amniotic fluid blood, neonatal blood and amniotic fluid

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Department of Epidemiology, Michigan State University

THE WAY IN WHICH VENTILATION IS THE WAY IN WHICH VENTILATION IS MANAGED IN PREMATURE INFANTS MANAGED IN PREMATURE INFANTS

MAY AFFECT THE CP RATEMAY AFFECT THE CP RATE

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Department of Epidemiology, Michigan State University

FOUR VENTILATORY RISK FACTORS IN INFANTS < 2 kgFOUR VENTILATORY RISK FACTORS IN INFANTS < 2 kg[Collins et al Pediatric Research 2001; 50:712-719][Collins et al Pediatric Research 2001; 50:712-719]

Mechanical ventilation Mechanical ventilation (MV)(MV) Requiring mechanical ventilatory assistanceRequiring mechanical ventilatory assistance

Prolonged ventilation Prolonged ventilation (P)(P) Duration of ventilation longer than expected for Duration of ventilation longer than expected for

GAGA

Hypocapnia Hypocapnia (C)(C)

Lowest quintile of cumulative PCOLowest quintile of cumulative PCO22 levels levels

Hyperoxia Hyperoxia (O)(O)

Highest quintile of cumulative POHighest quintile of cumulative PO22 levels levels

Page 20: The three types of biomedical research

Department of Epidemiology, Michigan State University

QUINTILES OF HYPOCAPNIA AND ODDS RATIO QUINTILES OF HYPOCAPNIA AND ODDS RATIO FOR DISABLING CP IN NBH STUDYFOR DISABLING CP IN NBH STUDY

1 1.1

2 2.1

5.3

0

1

2

3

4

5

6

Quintiles of PCO2

Q1 - HIGHQ2Q3Q4Q5 - LOW

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Department of Epidemiology, Michigan State University

ODDS RATIOS FOR DISABLING CP BY ODDS RATIOS FOR DISABLING CP BY VENTILATORY RISK FACTORS:VENTILATORY RISK FACTORS:

children with up to two risk factorschildren with up to two risk factors

1

2.72

4.2

7.1

0

1

2

3

4

5

6

7

8

no riskMV onlyMV + OMV + CMV + P

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Department of Epidemiology, Michigan State University

ODDS RATIOS FOR DISABLING CP BY ODDS RATIOS FOR DISABLING CP BY VENTILATORY RISK FACTORS:VENTILATORY RISK FACTORS:Children with up to four risk factorsChildren with up to four risk factors

0

10

20

30

40

50

60

no risk factorsMV onlyMV + OMV + C MV + PMV + COMV + CPMV + OPMV + COP

Page 23: The three types of biomedical research

THYROID THYROID HORMONESHORMONES

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Department of Epidemiology, Michigan State University

THYROID HORMONE AND THE THYROID HORMONE AND THE PREMATURE INFANTPREMATURE INFANT

When neonatal thyroid screening began in the When neonatal thyroid screening began in the

1970’s, premature infants frequently failed the 1970’s, premature infants frequently failed the

screen because of low total Tscreen because of low total T44. .

Because TSH was not elevated, and TBecause TSH was not elevated, and T44 eventually eventually

normalized, prematures with low levels of Tnormalized, prematures with low levels of T44 were were

not viewed with concern.not viewed with concern.

There is evidence however that “transient There is evidence however that “transient

hypothyroxinemia of prematurity” (THOP) may hypothyroxinemia of prematurity” (THOP) may

not be benign. not be benign.

Page 25: The three types of biomedical research

Department of Epidemiology, Michigan State University

EFFECTS OF NEONATAL EFFECTS OF NEONATAL THYROIDECTOMY IN THE RATTHYROIDECTOMY IN THE RAT

Decreased levels of growth factors, brain Decreased levels of growth factors, brain protein and RNA synthesisprotein and RNA synthesis

Less synaptogenesisLess synaptogenesis Reduction in enzymes necessary for nerve Reduction in enzymes necessary for nerve

terminal developmentterminal development Alterations in assembly of microtubule proteinsAlterations in assembly of microtubule proteins Delayed synthesis of myelin precursorsDelayed synthesis of myelin precursors Diminished synthesis of enzymes required for Diminished synthesis of enzymes required for

myelin synthesismyelin synthesis

Page 26: The three types of biomedical research

Department of Epidemiology, Michigan State University

THREE LARGE STUDIES OF NEONATAL THYROID THREE LARGE STUDIES OF NEONATAL THYROID LEVELS IN PREMATURES ALL FOUND WORSE LEVELS IN PREMATURES ALL FOUND WORSE

NEURODEVELOPMENT IN THOP BABIESNEURODEVELOPMENT IN THOP BABIES

EnglandEngland

• Lucas et al Lucas et al Arch Dis ChildArch Dis Child 1988;63:1201-6 1988;63:1201-6• Lucas et al Lucas et al BMJBMJ 1996;312:1133-4 1996;312:1133-4

HollandHolland• Meijer et al Meijer et al Arch Dis ChildArch Dis Child 1992; 67:944-7 1992; 67:944-7• Den Ouden et al Den Ouden et al Pediatric Res Pediatric Res 1996; 39:142-51996; 39:142-5

USA USA • Reuss et al Reuss et al New Eng J MedNew Eng J Med 1996;334:821-7 1996;334:821-7

Page 27: The three types of biomedical research

Department of Epidemiology, Michigan State University

THOP AND CEREBRAL PALSY BY GESTATIONAL AGE THOP AND CEREBRAL PALSY BY GESTATIONAL AGE

(T (T44 > 2.6 SD BELOW POPULATION MEAN) > 2.6 SD BELOW POPULATION MEAN)

0%

5%

10%

15%

20%

25%

30%

35%

22-27weeks

28-29weeks

30-31weeks

32-33weeks

From Reuss et al NEJM 1996;334:821

HT presentHT absent

Page 28: The three types of biomedical research

Department of Epidemiology, Michigan State University

THOP AND BAYLEY SCORES BY GESTATIONAL AGETHOP AND BAYLEY SCORES BY GESTATIONAL AGE (T (T44 > 2.6 SD BELOW POPULATION MEAN) > 2.6 SD BELOW POPULATION MEAN)

50

60

70

80

90

100

110

22-27weeks

28-29weeks

30-31weeks

32-33weeks

From Reuss et al NEJM 1996;334:821-7

HT presentHT absent

Page 29: The three types of biomedical research

Department of Epidemiology, Michigan State University

STEPWISE ADJUSTMENTS IN ASSSESSING STEPWISE ADJUSTMENTS IN ASSSESSING EFFFECTS OF THOP ON NEURODEVELOPMENT EFFFECTS OF THOP ON NEURODEVELOPMENT

ODDS RATIO FOR ODDS RATIO FOR CPCP

MDI SCORE MDI SCORE DIFFERENCESDIFFERENCES

UnadjustedUnadjusted 17.617.6 17.517.5

Adjusted for Adjusted for gestational agegestational age

10.810.8 15.415.4

Adjusted for GA and Adjusted for GA and 15 other variables15 other variables

3.53.5 9.99.9

Adjusted for GA and Adjusted for GA and 21 other variables21 other variables

4.44.4 6.86.8

From Reuss et al NEJM 1996;334:821-7

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Department of Epidemiology, Michigan State University

THESE RESULTS LED TO THE THOP 1 TRIALTHESE RESULTS LED TO THE THOP 1 TRIAL

Goal: Find dosage and administration method to Goal: Find dosage and administration method to maintain optimum thyroid hormone and TSH maintain optimum thyroid hormone and TSH patternpattern

Conducted in NY, Madrid and AmsterdamConducted in NY, Madrid and Amsterdam Six-arm study (N = 24 in each group)Six-arm study (N = 24 in each group)

– Placebo, IodinePlacebo, Iodine– Bolus TBolus T4: 4: 4 4 μμg vs 8 g vs 8 μμgg– Continuous TContinuous T4: 4: 4 4 μμg vs 8 g vs 8 μμgg

Continuous 4 Continuous 4 μμg raises Tg raises T4 4 acceptably with least acceptably with least suppression of TSHsuppression of TSH

12-hospital Phase 3 trial has been submitted to 12-hospital Phase 3 trial has been submitted to NIH, but will be underpowered for CP NIH, but will be underpowered for CP

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Department of Epidemiology, Michigan State University

Odds Ratios relating Magnesium and CP: seven studies

00.10.20.30.40.50.60.70.80.9

Page 32: The three types of biomedical research

Department of Epidemiology, Michigan State University

Two case control studies in very premature infants1 OR = 0.11 p <.05. Schendel 19962 OR = 0.15 p < .05. Nelson 1996

One cohort study in premature infants OR = 0.63 NS. Paneth 1997

Three randomized trials in premature labor1. RR = 0.83 NS (< 30 weeks) Crowther 2003

[mortality OR = 0.83, NS]1. RR = 0.63 NS (< 33 weeks) Marret 2008

[mortality OR = 0.79, NS]1. RR = 0.55 p < .05 (24-31 weeks) Rouse 2008

[mortality OR = 1.12, NS]

One randomized trial in pre-eclampsia. Magpie 2007 RR = 0.51 NS [mortality OR = 1.12, NS]

MAGNESIUM IN LABOR MIGHT PROTECT AGAINST CP

Page 33: The three types of biomedical research

Department of Epidemiology, Michigan State University

• CASE-CONTROL STUDIESCASE-CONTROL STUDIES

• Schendel al: JAMA 1996;276:1805-10.Schendel al: JAMA 1996;276:1805-10.

• Nelson et al: Pediatrics. 1996;97:780-2Nelson et al: Pediatrics. 1996;97:780-2

• COHORT STUDYCOHORT STUDY

• Paneth N et al: Paneth N et al: Pediatrics 1997;97:723.Pediatrics 1997;97:723.

• TRIALS TRIALS

• Crowther CA et al: JAMA 2003;290:2669-76Crowther CA et al: JAMA 2003;290:2669-76

• Marret et al:. Gynecol Obstet Fertil 2008; 36:278-Marret et al:. Gynecol Obstet Fertil 2008; 36:278-88.88.

• Rouse et al: N Engl J Med. 2008;28;359:895-905.Rouse et al: N Engl J Med. 2008;28;359:895-905.

• Magpie Trial Follow-Up Study Collaborative Magpie Trial Follow-Up Study Collaborative Group: BJOG. 2007; 114:289-99Group: BJOG. 2007; 114:289-99

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NEW MOLECULAR APPROACHES NEW MOLECULAR APPROACHES TO CP ETIOLOGYTO CP ETIOLOGY

USE OF NEONATAL BLOOD SPOTS USE OF NEONATAL BLOOD SPOTS ARCHIVED BY STATE OF MICHIGANARCHIVED BY STATE OF MICHIGAN

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Department of Epidemiology, Michigan State University

BLOOD SPOTS AVAILABLEBLOOD SPOTS AVAILABLE

85 randomly selected MI blood spots 85 randomly selected MI blood spots from 1996 – 2004from 1996 – 2004

Blood spots from 15 children with CP, Blood spots from 15 children with CP, including from two sets of twins including from two sets of twins discordant for CP. discordant for CP.

Freshly prepared blood spots from Freshly prepared blood spots from adults in a different study adults in a different study

Page 36: The three types of biomedical research

Department of Epidemiology, Michigan State University

MICROARRAY FINDINGSMICROARRAY FINDINGS

Fresh blood from adultsFresh blood from adults– Buffy coatBuffy coat 9,223 genes 9,223 genes – Whole bloodWhole blood 8,404 8,404

genesgenes– Filter paper spotFilter paper spot 7,067 genes7,067 genes

Newborn spotsNewborn spots– 1998 archived spot1998 archived spot 3,017 genes3,017 genes– 2000 archived spot2000 archived spot 3,211 genes3,211 genes– 2003 archived spot 2003 archived spot 3,644 genes3,644 genes– 2004 archived spot2004 archived spot 4,067 genes4,067 genes

Page 37: The three types of biomedical research

Department of Epidemiology, Michigan State University

Gene expression in archived newborn blood spots: Reliability in three runs and N of genes detected

Sample Year Average Correlation Standard Deviation Average N of genes

1998 .947 .017 3,017

2000 .894 .067 3,211

2003 . .887 .047 3,624

2004 .888 .048 4,067

All years .904 .042 3,480

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Department of Epidemiology, Michigan State University

QUANTITATIVE PCR FINDINGSQUANTITATIVE PCR FINDINGS[Julia Busik, MSU Dep’t of Physiology][Julia Busik, MSU Dep’t of Physiology]

mRNA mRNA retrievedretrieved

Required cycles of Required cycles of amplificationamplification

20042004 41 ng41 ng 22.922.9

20002000 55 ng55 ng 23.323.3

19971997 40 ng40 ng 27.827.8

Page 39: The three types of biomedical research

Department of Epidemiology, Michigan State University

Amplification plots and dissociation curves for triplicate analysis of 3 housekeeping genes and 2

inflammatory genes in 12 newborn spots produced 1998- 2004

Housekeeping genesCYC = cyclophyllinMRPL 11 =

mitochondrialribosomal proteinribosomal protein L 11HK1 = Hexokinase 1

Inflammatory genesITGAX = alpha X

integrinNFKB-1 = nuclear factor

kappa B-1

Page 40: The three types of biomedical research

SUMMARY OF THIS WORKSUMMARY OF THIS WORK Haak PT, Busik JV, Kort AJ, Haak PT, Busik JV, Kort AJ,

Tikhonenko M, Paneth N, Resau JH: Tikhonenko M, Paneth N, Resau JH:

Archived unfrozen neonatal blood Archived unfrozen neonatal blood spots are amenable to microarray spots are amenable to microarray

gene expression analysis. gene expression analysis.

NeonatologyNeonatology 2009;95:210-216. 2009;95:210-216.

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Department of Epidemiology, Michigan State University

MDCH Newborn Screening

21.5 Year Storage at MDCHMSU

RNA

Microarray qPCR Mycoplasma Virus

DNA

Unused

Amplification Plots

-1975

8025

18025

28025

38025

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

Cycles

Fluo

resc

ence

(dR)

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Department of Epidemiology, Michigan State University

LABORATORIES INVOLVEDLABORATORIES INVOLVED

Gene expressionGene expression– MicroarrayMicroarray – Van Andel Research Institute, – Van Andel Research Institute,

Grand Rapids, MI. T-32 fellows in perinatal Grand Rapids, MI. T-32 fellows in perinatal epidemiology - Pete Haak, Eric Kort MD; also epidemiology - Pete Haak, Eric Kort MD; also James Resau PhD, Kyle Furge PhDJames Resau PhD, Kyle Furge PhD

– qPCRqPCR – Julia Busik PhD, Physiology, MSU – Julia Busik PhD, Physiology, MSU Microbial DNAMicrobial DNA

– CMVCMV – Mark Schleiss MD, Pediatrics, U – Mark Schleiss MD, Pediatrics, U MinnesotaMinnesota

– MycoplasmaMycoplasma – Sainan Wei PhD, Rachel Fisher – Sainan Wei PhD, Rachel Fisher MB BCh, PhD, Pediatrics, MSUMB BCh, PhD, Pediatrics, MSU

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Department of Epidemiology, Michigan State University

SUMMARY OF CP EPIDEMIOLOGYSUMMARY OF CP EPIDEMIOLOGY

Found in about 1 in 500 school childrenFound in about 1 in 500 school children 40-fold higher risk in infants < 1,500 g40-fold higher risk in infants < 1,500 g CP has been increasing due to increased VLBW CP has been increasing due to increased VLBW

survival. This may now be levelling off or even survival. This may now be levelling off or even decliningdeclining

Not as closely linked to “birth asphyxia” as we Not as closely linked to “birth asphyxia” as we thoughtthought

Increasing evidence for a role of antepartum Increasing evidence for a role of antepartum infection, hormonal problems, ventilatory infection, hormonal problems, ventilatory management, especially in premature infantsmanagement, especially in premature infants

Archived newborn blood spots may be a useful Archived newborn blood spots may be a useful resource for understanding CPresource for understanding CP

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NIH- FUNDED T-32 TRAINING NIH- FUNDED T-32 TRAINING PROGRAM IN PERINATAL PROGRAM IN PERINATAL

EPIDEMIOLOGY AT MICHIGAN EPIDEMIOLOGY AT MICHIGAN STATE UNIVERSITYSTATE UNIVERSITY

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Department of Epidemiology, Michigan State University

TRAINING IN PERINATAL EPIDEMIOLOGY AT MSUTRAINING IN PERINATAL EPIDEMIOLOGY AT MSU

Program funded by NICHD in May 2005Program funded by NICHD in May 2005

The only T-32 training program in the nation The only T-32 training program in the nation focused solely on perinatal epidemiologyfocused solely on perinatal epidemiology

Support restricted by NIH rules to US Support restricted by NIH rules to US citizens/green card holderscitizens/green card holders

We have We have twotwo post-doctoral positions per year post-doctoral positions per year

Support is for two yearsSupport is for two years

Accepting applications for 2009-10 pending Accepting applications for 2009-10 pending refunding of program. refunding of program.

If interested, email cv, letter of interest to If interested, email cv, letter of interest to [email protected]@msu.edu

Page 46: The three types of biomedical research

THANKS FOR LISTENINGTHANKS FOR LISTENING

I’M HAPPY TO TAKE QUESTIONSI’M HAPPY TO TAKE QUESTIONS

(This presentation is posted at (This presentation is posted at http://

www.epi.msu.edu/faculty/paneth.htm

)