1. Perinatal/Pediatric Epidemiology at EBOH Brief history Current “catalog” of faculty & research areas Selected methodological contributions Impact

2. History Barry Pless arrived in 1975 – Chronic disease in children – Child injury Joined by Larson in 1976 and Kramer in 1978 Moffatt, Dougherty, Ducharme, Duffy (MCH) in 1980s Ciampi (1985), then Platt (1996) recruited in biostats Many pediatrician-epidemiologists at MCH since 2000 Kaufman, Basso, Naimi, and Yang in last few years

3. Current Faculty in Perinatal Epi Robert Platt Jay Kaufman Olga Basso Ashley Naimi Michael Kramer

4. Current Faculty in Pediatric Epi Beth Foster Mike Zappitelli Caroline Quach Jesse Papenburg Evelyn Constantin Patricia Li Meranda Nakhla Maryam Oskoui Patricia Fontela Moshe Ben-Shoshan Michael Kramer Robert Platt

5. Paradox: Intersecting Perinatal Mortality Curves First described by Yerushalmy in smokers vs nonsmokers (AJOG 1964) Low birth weight (LBW) ↑ in smokers Neonatal mortality ↓ in LBW births to smokers Reverse true for births >2500 g Cited by tobacco companies for decades Observed for all risk factors for LBW or preterm

6. 282930313233343536373839404142+ Gestational age (weeks) 1 10 100 1000 Perinatal deaths / 1,000 total births WhitesBlacks Crossover for Perinatal Mortality U.S. Blacks vs Whites, 1997

7. What ’ s the Appropriate Denominator? For total stillbirths, can use total births But for GA-specific stillbirth risk, total births at that GA is inappropriate – Conditions on birth at that GA – Reflects proportion of births born dead at that GA, not the risk of stillbirth at that GA – All fetuses at that GA are at risk for stillbirth – Argument made in 1987 (Yudkin et al, Lancet)

8. GA-Specific Stillbirth Rate Gestational age (weeks) 10 20 30 42 Livebirth1 Livebirth3 Livebirth2 Livebirth4 Livebirth5 Livebirth9 Livebirth6 Livebirth7 Livebirth8 Stillbirth1 100 per 1,000 fetuses at risk 500 per 1,000 total births

9. Appropriate Denominator: No Stillbirth Crossover

10. Fetuses at Risk and Neonatal Mortality Fetuses at a given GA are at risk of live birth within the next week All live births at risk of neonatal death All fetuses are at risk of neonatal death within the next week (Joseph et al 2003)

11. Fetuses at Risk: No Neonatal Mortality Crossover

12. The Preterm Birth Epidemic Canada, 1981-2010

13. U.S. Trends in Preterm Birth Non-Hispanic Whites and Blacks, 1981-2012

14. A Socially Contagious Disease Singleton Preterm Birth, U.S., 2009

15. Changes in PTB vs Induction U.S. States, 2002-04 vs 1992-94 r=+0.50 (+0.26, +0.68)

16. Potential for bias due to confounding and reverse causality: doubt about neurocognitive and growth/obesity benefits Best way to minimize bias: RCT But randomization to breast- vs artificial feeding is infeasible and may be unethical Initial feeding choice made before birth; prenatal interventions are difficult and expensive Solution: RCT of intervention to promote BF exclusivity and duration, with analysis by intention to treat Overlap of BF behaviours requires very large sample size Studying Child Health Benefits of Breastfeeding

17. PROBIT PROmotion of Breastfeeding Intervention Trial A Cluster-Randomized Trial in the Republic of Belarus

18. Design Intervention based on WHO/UNICEF Baby-Friendly Hospital Initiative RCT using cluster randomization Clusters randomized: 31 maternity hospitals and one affiliated polyclinic per hospital 17,046 healthy BF newborns >37 weeks and >2500 g enrolled during postpartum stay Sample size based on primary outcome: 10% reduction in risk of GI infection during infancy Births occurred June 1996 to December 1997

19. Baby-Friendly Hospital Initiative Have a written BF policy Train staff to implement policy Inform mothers about BF benefits Help mothers begin BF within 30 min of birth Show mothers how to BF and maintain BF Give healthy newborns breast milk only Practice rooming-in 24 hours per day Encourage BF on demand Give no pacifiers to BF infants Foster and refer mothers to BF support groups

20. Duration of Breastfeeding

21. Degree of Breastfeeding (%)

22. PROBIT resulted in 2 cohorts that differed substantially in exclusivity/duration of BF – These differences were created by randomization, not choice of mother or doctor – This has enabled strong causal inferences with respect to BF effects on long-term outcomes PROBIT II: age 6.5 years, data 2002-2005 PROBIT III: age 11.5 years, data 2008-2010 PROBIT IV: age 16 years, data 2012-2015 PROBIT Follow-Up

23. Impact CHIRPP (1990) CPSS (1995) WHA: exclusive breastfeeding 6 mo (2001) Reduction in preterm birth since mid-2000s