Methodological challenges in studying the causal determinants of child growth.

Background: Previous studies of early life influences on later growth in childhood have varied in their analytical approaches, particularly with respect to 'adjustment' for differences in size at the beginning of the growth period examined. Methods: We compared three commonly used statistical models to assess the effect of maternal body mass index (BMI) on growth between 6.5 and 11.5 years in a large cohort of Belarusian children, as follows: (Model 1) analysis of the difference in anthropometric measurements between the two ages; (Model 2) analysis of the measurement at 11.5 years after adjustment for the same measurement at 6.5 years; and (Model 3) analysis of the difference in measurements after adjustment for the measurement at 6.5 years (mathematically identical to Model 2). Results: Among PROBIT children of obese mothers (BMI ≥ 30 kg/m 2 ) vs those of mothers with normal BMI (18.5 to < 25 kg/m 2 ), Model 1 yielded larger increases in most weight and adiposity outcomes than did Model 2. We show that these larger effects arise because Model 2 parameterizes the effect of maternal BMI twice in same model: once for its effect on size at 6.5 years, and a second time for its effect on growth over the 5-year period between 6.5 and 11.5 years. Similar results were obtained in analogous analyses from cohorts in Boston, MA, and Singapore. Conclusion: Analysing the effect of exposure on change in outcome between two ages (Model 1) is clearly preferable to 'adjustment' for the outcome at the earlier age whenever the exposure under study affects the outcome at the earlier age.