The effect of maternal pre-pregnancy body mass index on hypertensive disorders of pregnancy (HDP): a systematic review and dose-response meta-analysis of cohort studies involving 50 million pregnancies.

Background: Hypertensive disorders of pregnancy is a prevalent pregnancy complication worldwide, and the dose-response association between maternal pre-pregnancy body mass index (BMI) and hypertensive disorders of pregnancy has not been precisely studied. The aim of this study was to assess dose-response association between maternal pre-pregnancy BMI and hypertensive disorders of pregnancy, including pregnancy induced hypertension, preeclampsia and eclampsia.

Methods: This dose-response meta-analysis searched four electronic databases (Pubmed, Web of science, OVID Embase and OVID Medline) for relevant publications up to October, 2023. Cohort studies evaluated the association between pre-pregnancy or early pregnancy maternal BMI and pregnancy induced hypertension, preeclampsia, eclampsia and hypertensive disorders of pregnancy were included. Non-linear or linear dose-response association was modeled. Unadjusted and adjusted effects were pooled separately, and four subgroups, meta-regression, five sensitivity analyses were conducted. Study protocol was registered on the PROSPERO (CRD42022290318).

Findings: 157 cohort studies involving 51,813,975 pregnancies were finally included. Of 157 studies, multiple outcomes were reported: 58 on pregnancy induced hypertension, 92 on preeclampsia, 6 on eclampsia, and 84 on hypertensive disorders of pregnancy, have assessed the association with pre-pregnancy BMI. A significant linear dose-response relationship was identified between BMI and pregnancy induced hypertension with a crude relative risk (cRR) of BMI per 5-unit increase of 1.73 (95% confidence intervals [CI]: 1.65-1.81), and an adjusted odds ratio (aOR) per 5-unit increase of 1.82 (95% CI: 1.74-1.90). Similar dose-response relationship was observed between BMI and preeclampsia (cRR: 1.63, 1.58-1.69; aOR: 1.70, 1.61-1.80), eclampsia (cRR: 1.40, 1.28-1.53; aOR: 1.36, 1.20-1.53) and hypertensive disorders of pregnancy (cRR: 1.68, 1.63-1.74; aOR: 1.75, 1.68-1.82). Subgroup analyses revealed that the pooled risk of BMI for pregnancy induced hypertension, preeclampsia, eclampsia, and hypertensive disorders of pregnancy was likely higher in Asian pregnant women compared to those in American and European regions. Sensitivity analyses results were mainly consistent with the primary results.

Interpretation: This meta-analysis demonstrated a clear and significant dose-response relationship between increasing maternal pre-pregnancy BMI and elevated risks of pregnancy induced hypertension, preeclampsia, eclampsia, and overall hypertensive disorders of pregnancy, underscoring the clinical importance of maintaining a healthy BMI prior to conception. Pre-pregnancy BMI may be an important focus for preconception counseling and subsequent pre-pregnancy weight management for both clinicians and women.

Funding: National Natural Science Foundation of China (72174132, 82474335, 82225049), Natural Science Foundation of Sichuan Province (2024NSFSC1668, 2024YFFK0152), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD23004).