perinatal/pediatric epidemiology at eboh brief history current “catalog” of faculty &...
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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