the three types of biomedical research
TRANSCRIPT
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
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.
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
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
Department of Epidemiology, Michigan State University
William Osler wrote the only19th century monograph on CP published in the US
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
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
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
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.
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
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.
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?
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%
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
INFECTION AND INFECTION AND INFLAMMATIONINFLAMMATION
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.
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
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
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
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
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
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
THYROID THYROID HORMONESHORMONES
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.
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
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
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
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
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
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
Department of Epidemiology, Michigan State University
Odds Ratios relating Magnesium and CP: seven studies
00.10.20.30.40.50.60.70.80.9
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
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
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
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
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
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
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
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
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.
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)
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
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
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
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
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
)