Evaluating causal influence of maternal educational attainment on offspring birthweight via observational study and Mendelian randomization analyses

Abstract

BackgroundAlthough extensive discussions on the influence of maternal educational attainment on offspring birthweight, the conclusion remains controversial, and it is challenging to comprehensively assess the causal association between them. MethodsTo estimate effect of maternal educational attainment on the birthweight of first child, we first conducted an individual-level analysis with UK Biobank participants of white ancestry (n = 208,162). We then implemented Mendelian randomization (MR) methods including inverse variance weighted (IVW) MR and multivariable MR to assess the causal relation between maternal education and maternal-specific birthweight. Finally, using the UK Biobank parent-offspring trio data (n = 618), we performed a polygenic score based MR to simultaneously adjust for confounding effects of fetal-specific birthweight and paternal educational attainment. We also conducted simulations for power evaluation and sensitivity analyses for horizontal pleiotropy of instruments. ResultsWe observed that birthweight of first child was positively influenced by maternal education, with 7 years of maternal education as the reference, adjusted effect = 44.8 (95%CIs 38.0–51.6, P = 6.15 × 10−38), 54.9 (95%CIs 47.6–62.2, P = 4.21 × 10−128), and 89.4 (95%CIs 82.1–96.7, P = 4.28 × 10−34) for 10, 15 and 20 years of maternal educational attainment, respectively. A causal relation between maternal education and offspring birthweight was revealed by IVW MR (estimated effect = 0.074 for one standard deviation increase in maternal education years, 95%CIs 0.054–0.093, P = 2.56 × 10−13) and by complementary MR methods. This connection was not substantially affected by paternal education or horizontal pleiotropy. Further, we found a positive but insignificant causal association (adjusted effect = 24.0, 95%CIs −150.1–198.1, P = 0.787) between maternal education and offspring birthweight after simultaneously controlling for fetal genome and paternal education; this null causality was largely due to limited power of small sample sizes of parent-offspring trios. ConclusionThis study offers supportive evidence for a causal association between maternal education and offspring birthweight, highlighting the significance of enhancing maternal education to prevent low birthweight.