Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes

• Published in: JAMA Network Open
• Main Authors: Rogne, Tormod, Gill, Dipender, Liew, Zeyan, Shi, Xiaoting, Stensrud, Vilde Hatlevoll, Nilsen, Tom Ivar Lund, Burgess, Stephen
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Medical Association (AMA) 2024
• Subjects: Iceland
• Online Access: http://dx.doi.org/10.1001/jamanetworkopen.2023.51166; https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2813841/rogne_2024_oi_231500_1704316007.29047.pdf

Importance Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association. Objective To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors. Design, Setting, and Participants In this 2-sample mendelian randomization (MR) cohort study, uncorrelated ( R 2 < 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure ( P < 5 × 10 −8 ) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance–weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023. Exposure Genetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure. Main Outcomes and Measures Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight. Results The analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ...