{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:15:29Z","timestamp":1791594929896,"version":"4.3.4"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2<\/jats:sup><\/jats:italic> &amp;lt; 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P<\/jats:italic> &amp;lt; 5 \u00d7 10\u22128<\/jats:sup>) 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\u2013weighted 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.<\/jats:p><\/jats:sec>Exposure<\/jats:title>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.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight.<\/jats:p><\/jats:sec>Results<\/jats:title>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\u202f002 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 ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from \u221217% (95% CI, \u221246% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.51166","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T16:00:46Z","timestamp":1704988846000},"page":"e2351166","source":"Crossref","is-referenced-by-count":66,"title":["Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes"],"prefix":"10.1001","volume":"7","author":[{"given":"Tormod","family":"Rogne","sequence":"first","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut"},{"name":"Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipender","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and 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