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ALSPAC AND CROSS-COHORT STUDIES Causal Effects of Breastfeeding on Child Health Outcomes

ALSPAC AND CROSS-COHORT STUDIES Causal Effects of Breastfeeding on Child 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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ALSPAC AND CROSS-COHORT STUDIES Causal Effects of Breastfeeding on Child Health Outcomes

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  1. ALSPAC AND CROSS-COHORT STUDIESCausal 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

  2. 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 **

  3. What are the causal effects of breastfeedingon IQ, obesity and blood pressure?Evidence from comparing high-incomewith middle-income cohorts Marie-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

  4. 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

  5. less smoking healthy diet better living conditions physical activity higher socioeconomic position healthier families education Causal effects ??

  6. 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

  7. Analyses • Associations of indicators of SEP with breastfeeding • Maternal education • paternal education • family income • occupational social class • Associations of breastfeeding duration with child outcomes:

  8. Breastfeeding by income 70 60 Breastfeeding prevalence 50 40 30 0 .2 .4 .6 .8 1 Cumulative proportion of the population according to income ALSPAC Pelotas 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)

  9. ORs for breastfeeding by income 10 9 8 7 6 OR 5 4 3 2 1 0 ALSPAC Pelotas Cohort

  10. BMI

  11. less smoking Discordant ALSPAC-Pelotas healthy diet better living conditions physical activity higher socioeconomic position healthier families education Causal effects ??

  12. Breastfeeding categories: 0 to <1m; 1 to <3m; 3 to <6m; 6m or more Fully adjusted models

  13. ALSPAC-PELOTAS BREASTFEEDING ASSOCIATIONS CHILD OUTCOME EFFECT SIZE (95% CI) SBP (mmHg) ALSPAC -0.35 (-0.55, -0.14) Pelotas -0.13 (-0.83, 0.57) p hetero = 0.6 DBP (mmHg) ALSPAC -0.16 (-0.31, -0.01) Pelotas 0.05 (-0.50, 0.60) p hetero = 0.5 BMI (kg/m2) ALSPAC -0.16 (-0.22, -0.09) Pelotas 0.14 (-0.07, 0.36) p hetero = 0.009 IQ ALSPAC 0.97 (0.62, 1.32) Pelotas 1.97 (0.88, 3.05) p hetero = 0.09 -1 -.5 0 0 .5 1 1.5 2 2.5 3 3.5

  14. ALSPAC-PELOTAS BREASTFEEDING ASSOCIATIONS ALSPAC-LMIC COHORT CONSORTIUM BREASTFEEDING ASSOCIATIONS CHILD OUTCOME EFFECT SIZE (95% CI) CHILD OUTCOME EFFECT SIZE (95% CI) SBP (mmHg) SBP (mmHg) ALSPAC -0.35 (-0.55, -0.14) Pelotas -0.13 (-0.83, 0.57) ALSPAC -0.35 (-0.55, -0.14) p hetero = 0.6 COHORT 0.12 (-0.01, 0.24) p hetero <0.001 DBP (mmHg) ALSPAC -0.16 (-0.31, -0.01) Pelotas 0.05 (-0.50, 0.60) DBP (mmHg) p hetero = 0.5 ALSPAC -0.16 (-0.31, -0.01) COHORT 0.10 (-0.01, 0.20) BMI (kg/m2) p hetero = 0.005 ALSPAC -0.16 (-0.22, -0.09) Pelotas 0.14 (-0.07, 0.36) p hetero = 0.009 BMI (kg/m2) ALSPAC -0.16 (-0.22, -0.09) IQ ALSPAC 0.97 (0.62, 1.32) COHORT 0.04 (0.00, 0.08) Pelotas 1.97 (0.88, 3.05) p hetero <0.001 p hetero = 0.09 -1 -.5 0 0 .5 1 1.5 2 2.5 3 3.5 -1 -.5 0 0 .5 1 1.5 2 2.5 3 3.5

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

  16. Using the totality of the evidence

  17. Integrating cross-cohorts and additional causal approaches Maternal 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)

  18. Multi-method approach for assessing intrauterine mechanisms

  19. Multivariable Regression

  20. Cross-cohort confounders

  21. Maternal-Paternal Comparisons

  22. Prenatal-Postnatal Comparisons

  23. Single Method Approach • Conventional multivariable regression • independent associations of maternal smoking and child aggression • intrauterine effects as a possible explanation

  24. 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

  25. 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

  26. 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

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