Perinatal/Pediatric Epidemiology at EBOH

• Brief history

• Current “catalog” of faculty & research areas

• Selected methodological contributions

• Impact

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

Current Faculty in Perinatal Epi

• Robert Platt

• Jay Kaufman

• Olga Basso

• Ashley Naimi

• Michael Kramer

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

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

28 29 30 31 32 33 34 35 36 37 38 39 40 41 42+

Gestational age (weeks)

1

10

100

1000

Per

inat

al d

eath

s /

1,00

0 to

tal

bir

ths

Whites Blacks

Crossover for Perinatal MortalityU.S. Blacks vs Whites, 1997

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)

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

28 29 30 31 32 33 34 35 36 37 38 39 40 41 42+

Gestational age (weeks)

0

0.5

1

1.5

2

2.5

Stil

lbir

th r

ate

per

1,00

0 fe

tuse

s at

ris

k

Whites Blacks

Appropriate Denominator: No Stillbirth Crossover

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)

Fetuses at Risk: No Neonatal Mortality Crossover

28 29 30 31 32 33 34 35 36 37 38 39 40 41 42+

Gestational age (weeks)

0

0.5

1

1.5

Neo

nata

l dea

ths

/ 1,0

00 fe

tuse

s at

ris

k

Whites Blacks

The Preterm Birth Epidemic Canada, 1981-2010

6

6.5

7

7.5

8

8.5

1981

1983

1985

1987

1989

1991

1993

1995

1997

1999

2001

2003

2005

2007

2009

Births <37 wk (%)

U.S. Trends in Preterm BirthNon-Hispanic Whites and Blacks, 1981-2012

6

8

10

12

14

16

18

20

Whites Blacks

A Socially Contagious DiseaseSingleton Preterm Birth, U.S., 2009

Changes in PTB vs InductionU.S. States, 2002-04 vs 1992-94

-10 -5 0 5 10 15 20 25-2

-1

0

1

2

3

4

Change in induction (%)

Ch

an

ge

in p

rete

rm (

%)

r=+0.50 (+0.26, +0.68)

• 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

PROBIT

PROmotion of Breastfeeding Intervention Trial

A Cluster-Randomized Trial in the Republic of Belarus

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

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

Duration of Breastfeeding

0 30 60 90 120 150 180 210 240 270 300 330 360

Age in days

0

0.2

0.4

0.6

0.8

1Proportion Still Breastfeeding

Control Experimental

Degree of Breastfeeding (%)

0 10 20 30 40 50 60

Exclusive at 6 mo

Exclusive at 3 mo

Predominant at 6 mo

Predominant at 3 mo

Control Experimental

• 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

Impact

• CHIRPP (1990)

• CPSS (1995)

• WHA: exclusive breastfeeding 6 mo (2001)

• Reduction in preterm birth since mid-2000s