School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL ALSPAC AND CROSS-COHORT STUDIES Causal Effects of Breastfeeding on Child Health Outcomes.

School ofSOCIAL AND COMMUNITY

MEDICINE

University ofBRISTOL

ALSPAC AND CROSS-COHORT STUDIES

Causal Effects of Breastfeeding onChild Health Outcomes

Marie-Jo Brion

Sir Henry Wellcome Postdoctoral Fellow

MRC Centre for Causal Analyses in Translational Epidemiology

School of Social and Community Medicine

University of Bristol


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Cause and Effect in Observational Studies:

Getting the Right Answer Examples where observational studies and RCTs fail to arrive at

the same answer

Protective effects on CVD from observational studies : Beta carotene Vitamin E supplements Vitamin C supplements Hormone replacement therapy

Large RCTs showed no protective effect

Likely explanation: confounding in particular, confounding by socioeconomic position

** NEED BETTER CAUSAL APPROACHES **


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What are the causal effects of breastfeeding

on IQ, obesity and blood pressure?

Evidence from comparing high-income

with middle-income cohortsMarie-Jo Brion, Debbie Lawlor, Alicia Matijasevich, Bernardo Horta, Luciana Anselmi,

Ana Maria B Menezes, Cesar Victora, George Davey Smith

Brion et al (2011) IJE 40(3): 670


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Objectives

Explore novel approach for improving causal inference in observational studies

Comparing associations from HIC to LMIC cohorts where associations of confounders with health outcomes are likely to differ between cohorts

Assessing causal effects of breastfeeding on child BP, BMI and IQ


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higher socioeconomic position

healthy diet

physical activity

healthier families

education

Causal effects ??

less smoking

better living conditions


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Methods ALSPAC, UK (N~5000) and Pelotas 1993, Brazil (N~1000)

Meta-analyses of 5 LMIC (COHORTS consortium; N~11,000)Fall et al., IJE 2011

Randomised trial of breastfeeding promotion (PROBIT Belarus trial)Kramer et al., Arch Gen Psychiatry 2008; Kramer et al., AJCN 2007


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Analyses Associations of indicators of SEP with breastfeeding

Maternal education paternal education family income occupational social class

Associations of breastfeeding duration with child outcomes:


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Prevalence (%)

Breastfeeding duration Pelotas ALSPAC

0 to <1 month 15.6% 36.8 %

1 to < 3 months 25.4% 15.6 %

3 to < 6 months 23.6% 13.7 %

6 months or more 35.3% 33.9 %

Ever breastfed 96.8% 84.3%

Exclusive breastfeeding at 2 months 65.7% 38.3%


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Breastfeeding at 3 months according to family income

2030

4050

6070

8090

100

1 2 3 4 5

Income (Low to High)

Bre

as

tfe

ed

ing

at

3 m

on

ths

(%

)

Pelotas

ALSPAC

Ever breastfed according to family income

3040

50607080

90100

1 2 3 4 5

Income (Low to High)P

erc

en

t e

ve

r b

rea

stf

ed

(%

) Pelotas

ALSPAC


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Relative/Slope Index of Inequality

Logistic regression: SEP indicator with binary outcomes Odds of outcome in highest SEP level (1) versus the lowest (0)

Linear regression: SEP indicator with continuous outcomes Difference in outcome between highest SEP level (1) and the lowest (0)

3040

5060

70

Bre

astfe

edin

g pr

eval

ence

0 .2 .4 .6 .8 1

Cumulative proportion of the population according to income

ALSPAC Pelotas

Breastfeeding by income


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01

23

45

67

89

10O

R

ALSPAC PelotasCohort

ORs for breastfeeding by social class

02

46

810

1214

16O

R


ORs for breastfeeding by maternal education

01

23

45

67

89

10O

R


ORs for breastfeeding by paternal education

01

23

45

67

89

10O

R


ORs for breastfeeding by income


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-6-4

-20

-6-4

-20

ALSPAC Pelotas ALSPAC Pelotas

class income

maternal education paternal education

diffe

renc

e in

SB

P (

mm

Hg

)Systolic BP

-4-2

02

-4-2

02


class income


diffe

renc

e in

DB

P (

mm

Hg)

cohort

Diastolic BP-1

01

2-1

01

2


class income


diffe

renc

e in

BM

I (kg

/m2

)

510

1520

255

1015

2025


class income

maternal education paternal educationdi

ffere

nce

in IQ

IQBMI


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higher socioeconomic position

healthy diet

physical activity

healthier families

education

Causal effects ??

less smoking

better living conditions

Discordant ALSPAC-Pelotas


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Mean difference in outcome by breastfeeding category

OutcomeALSPAC

β (95% CI) P trend

Pelotas

β (95% CI) P trend

SBP, -0.35 (-0.55, -0.14) 0.001 -0.13 (-0.83, 0.57) 0.7(mmHg)

DBP -0.16 (-0.31, -0.01) 0.04 0.05 (-0.50, 0.60) 0.9(mmHg)

BMI -0.16 (-0.22, -0.09) <0.001 0.14 (-0.07, 0.36) 0.2(kg/m2)

IQ 0.97 (0.62, 1.32) <0.001 1.97 (0.88, 3.05) <0.001

Breastfeeding categories: 0 to <1m; 1 to <3m; 3 to <6m; 6m or more

Fully adjusted models


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SBP (mmHg)ALSPACPelotas

p hetero = 0.6

DBP (mmHg)ALSPACPelotas

p hetero = 0.5

BMI (kg/m2)ALSPACPelotas

p hetero = 0.009

IQALSPACPelotas

p hetero = 0.09

CHILD OUTCOME

-0.35 (-0.55, -0.14)-0.13 (-0.83, 0.57)

-0.16 (-0.31, -0.01) 0.05 (-0.50, 0.60)

-0.16 (-0.22, -0.09) 0.14 (-0.07, 0.36)

0.97 (0.62, 1.32)1.97 (0.88, 3.05)

EFFECT SIZE (95% CI)

0-1 -.5 0 .5 1 1.5 2 2.5 3 3.5

ALSPAC-PELOTAS BREASTFEEDING ASSOCIATIONS


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SBP (mmHg)ALSPACPelotas

p hetero = 0.6

DBP (mmHg)ALSPACPelotas

p hetero = 0.5

BMI (kg/m2)ALSPACPelotas

p hetero = 0.009

IQALSPACPelotas

p hetero = 0.09

CHILD OUTCOME

-0.35 (-0.55, -0.14)-0.13 (-0.83, 0.57)

-0.16 (-0.31, -0.01) 0.05 (-0.50, 0.60)

-0.16 (-0.22, -0.09) 0.14 (-0.07, 0.36)

0.97 (0.62, 1.32)1.97 (0.88, 3.05)


0-1 -.5 0 .5 1 1.5 2 2.5 3 3.5

ALSPAC-PELOTAS BREASTFEEDING ASSOCIATIONS

SBP (mmHg)ALSPACCOHORT

p hetero <0.001

DBP (mmHg)ALSPACCOHORT

p hetero = 0.005

BMI (kg/m2)ALSPACCOHORT

p hetero <0.001

CHILD OUTCOME

-0.35 (-0.55, -0.14) 0.12 (-0.01, 0.24)

-0.16 (-0.31, -0.01) 0.10 (-0.01, 0.20)

-0.16 (-0.22, -0.09) 0.04 (0.00, 0.08)


0-1 -.5 0 .5 1 1.5 2 2.5 3 3.5

ALSPAC-LMIC COHORT CONSORTIUM BREASTFEEDING ASSOCIATIONS


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Comparison Method Validation

ALSPAC Strong socioeconomic

patterning in breastfeeding

PelotasWeak socioeconomic patterning

in breastfeeding

BelarusRandomised

Trial

Association with any breastfeeding (per category)* Effect of breastfeeding intervention

Outcome β 95% CI P β 95% CI P Difference in outcome

95% CI

SBP, mmHg -0.35 -0.55, -0.14 0.001 -0.13 -0.83, 0.57 0.7 0.2 -2.9, 3.3

DBP, mmHg -0.16 -0.31, -0.01 0.04 0.05 -0.50, 0.60 0.9 0.2 -1.8, 2.2

BMI, kg/m2 -0.16 -0.22, -0.09 <0.001 0.14 -0.07, 0.36 0.2 0.1 -0.2, 0.3

IQ 0.97 0.62, 1.32 <0.001 1.97 0.88, 3.05 <0.001 5.9 -1.0, 12.8

* Adjusted for all indicators of maternal education, paternal education, family income, occupational social class


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Using the totality of the evidence


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Integrating cross-cohorts and additional

causal approachesMaternal prenatal smoking and child aggression:

Exploring intrauterine effects in UK, Australian and

Brazilian cohorts

Marie-Jo Brion, Monique Robinson, Alicia Matijasevich, Colin Steer, Luciana Anselmi, Ana Menezes, Craig Pennell, Lyle Palmer, Cesar Victora, George Davey Smith, Debbie Lawlor

Brion et al. (under review)


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Multi-method approach for assessing intrauterine

mechanisms


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Multivariable Regression


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Cross-cohort confounders


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Maternal-Paternal Comparisons


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Prenatal-Postnatal Comparisons


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Single Method Approach

Conventional multivariable regression independent associations of maternal smoking

and child aggression intrauterine effects as a possible explanation


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Totality of Evidence From Multiple Methods

Total evidence for intrauterine effects is weak Not consistent with SEP being primary / sole determinant Confounding by other familial factors


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ALSPAC and Cross-Cohort Studies

ALSPAC integrated with additional cohorts to explore cross-cohort approach for improving causal inference based on conventional method alone

Value of integrating multiple methods for assessing causal mechanisms to arrive at conclusions based on totality of evidence

Breastfeeding and child BMI, BP and IQ Evidence supporting causal effects breastfeeding duration on greater IQ

Maternal prenatal smoking and child aggression Weak evidence for intrauterine mechanisms Not consistent with SEP being the main explanation for the association Other family-level confounders are likely


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Acknowledgements CAiTE, University of Bristol

Debbie Lawlor George Davey Smith Colin Steer

Federal University of Pelotas Cesar Victora Alicia Matijasevich Bernardo Horta

Other Co-authors: Monique Robinson, Craig Pennell, Lyle Palmer Luciana Anselmi, Ana Menezes

Wellcome Trust UK Henry Wellcome Postdoctoral Fellowship

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL ALSPAC AND CROSS-COHORT STUDIES Causal Effects of Breastfeeding on Child Health Outcomes.

Documents

iq slide

pelotas n

iq alspac n

bmi alspac n

causal analyses

sbpdbp alspac n

brazil n

observational studies