Re-examining the link between prenatal maternal anxiety and child emotional difficulties, using a sibling design

Background: Prenatal exposure to maternal anxiety has been associated with child emotional difficulties in a number of epidemiological studies. One key concern, however, is that this link is vulnerable to confounding by pleiotropic genes or environmental family factors. Methods: Data on 82 383 mothers and children from the population-based Mother and Child Cohort Study and data on 21 980 siblings were used in this study. Mothers filled out questionnaires for each unique pregnancy, for infant difficulties at 6 months and for emotional difficulties at 36 months. The link between prenatal maternal anxiety and child difficulties were examined using logistic regression analyses and multiple linear regression analyses for the full study sample and the sibling sample. Results: In the conventional full-cohort analyses, prenatal exposure to maternal anxiety was associated with child difficulties at both 6 months [odds ratio (OR) = 2.1 (1.94-2.27)] and 36 months [OR = 2.72 (2.47-2.99)]. The findings were essentially the same whether we examined difficulties at 6 months or at 36 months. However, these associations were no longer present once we controlled for potential social and genetic confounders in the sibling comparison analyses, either at 6 months [OR = 1.32 (0.91-1.90)] or at 36 months [OR = 1.28 (0.63-2.60)]. Findings from multiple regression analyses with continuous measures were essentially the same. Conclusions: Our finding lends little support for there being an independent prenatal effect on child emotional difficulties; rather, our findings suggest that the link between prenatal maternal anxiety and child difficulties could be confounded by pleiotropic genes or environmental family factors.