Does fetal growth restriction cause later obesity? Pitfalls in analyzing causal mediators as confounders

Michael S. Kramer*, Xun Zhang, Mourad Dahhou, Seungmi Yang, Richard M. Martin, Emily Oken, Robert W. Platt

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)
159 Downloads (Pure)

Abstract

Recent studies finding that small-for-gestational-age (SGA) birth is associated with increased adiposity in childhood and adulthood have been based on analyses "adjusting" for height, weight, or body mass index (BMI; weight (kg)/height (m)2) measured concurrently with the adiposity measurement. To assess the potential for bias due to overadjustment for a causal mediator, we compared 2 approaches to analyzing the association between SGA birth and adiposity outcomes (skinfold thicknesses and bioelectrical impedance measurement of body fat) at age 11.5 years using the same data set in a cohort of Belarusian children followed from birth in 1996-1997 to age 11.5 years in 2008-2010. We 1) studied the association of SGA birth with adiposity, adjusting for baseline covariates only, and 2) made additional regression adjustment for concurrent height, weight, or BMI. The first approach yielded negative associations between SGA birth and all adiposity outcomes. Additional adjustment for concurrent weight or BMI reversed (i.e., to positive) the SGA-adiposity association. To explore the latter anthropometric measures as causal mediators, we also used marginal structural models to estimate the controlled direct effect of SGA birth. That effect was similar to the effect seen with the first approach when modeled on height, was null when modeled on BMI, but was confounded by differences in lean mass versus fat mass when modeled on weight.

Original languageEnglish
Pages (from-to)585-590
Number of pages6
JournalAmerican Journal of Epidemiology
Volume185
Issue number7
Early online date3 Mar 2017
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • Bias
  • Causal inference
  • Life-course epidemiology
  • Marginal structural models
  • Obesity
  • Small-for-gestational-age birth

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