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- Title
Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes: A Mendelian Randomization Study.
- Authors
Rogne, Tormod; Gill, Dipender; Liew, Zeyan; Shi, Xiaoting; Stensrud, Vilde Hatlevoll; Nilsen, Tom Ivar Lund; Burgess, Stephen
- Abstract
Key Points: Question: Which pathways mediate the inequity in pregnancy health associated with low educational attainment? Findings: In this cohort study of more than 3 million individuals, an association between genetically estimated lower educational attainment and increased risk of ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring low birth weight was observed. A sizeable portion of these associations were explained by targetable risk factors. Meaning: These findings suggest that the association of socioeconomic inequalities with adverse pregnancy outcomes may be reduced by intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure. This cohort study evaluates the mediating pathways underlying the association between educational attainment and pregnancy complications and including ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight. 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 (R2 < 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 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 −17% (95% CI, −46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses. Conclusions and Relevance: 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.
- Subjects
ICELAND; UNITED States; UNITED Kingdom; FINLAND; CARDIOVASCULAR diseases risk factors; STATISTICS; HDL cholesterol; MORNING sickness; CONFIDENCE intervals; PREMATURE infants; PSYCHOLOGY of mothers; SINGLE nucleotide polymorphisms; MULTIVARIATE analysis; SYSTOLIC blood pressure; REGRESSION analysis; PUBLIC health; PREGNANCY outcomes; GENOME-wide association studies; COMPARATIVE studies; TYPE 2 diabetes; PREECLAMPSIA; RISK assessment; PREGNANCY complications; DESCRIPTIVE statistics; BIRTH weight; RESEARCH funding; MOLECULAR epidemiology; BODY mass index; SMOKING; ODDS ratio; HEALTH equity; ECTOPIC pregnancy; GESTATIONAL diabetes; EDUCATIONAL attainment; LONGITUDINAL method; EPIDEMIOLOGICAL research
- Publication
JAMA Network Open, 2024, Vol 7, Issue 1, pe2351166
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2023.51166