Differences in Risk Factors for Severe Preeclampsia and HELLP Syndrome in Singleton Versus Twin Pregnancies: A Population‐Based Cohort Study

Objective To examine whether the associations between pre‐pregnancy risk factors and severe preeclampsia/eclampsia (SPE) and/or HELLP syndrome differ between singleton and twin pregnancies. Design A population‐based retrospective cohort study. Setting British Columbia (BC), Canada. Population All pregnancies with singletons or twins that resulted in a stillbirth or live birth at ≥ 20 weeks' gestation from 2008/09 to 2020/21. Methods Data were obtained from the BC Perinatal Database Registry. Logistic regression was used to estimate the association between each risk factor for SPE/HELLP (e.g., body‐mass‐index (BMI), in vitro‐fertilisation (IVF), chronic hypertension, and diabetes) and the modifying effect of plurality by including interaction terms between these risk factors and plurality in the model. Main Outcome Measures Severe preeclampsia, eclampsia, and/or HELLP syndrome. Results Among 563 252 pregnancies (8841 twin, 554 411 singleton), the rate of SPE/HELLP was 4.7 per 1000 singleton pregnancies and 31.1 per 1000 twin pregnancies (relative risk 6.61; 95% confidence interval (CI) 5.84–7.49). Older maternal age (≥ 35 years), nulliparity, pre‐pregnancy and gestational diabetes, chronic hypertension, prior mental health problems, substance use during pregnancy, and prior stillbirth increased the odds, while smoking decreased the odds of SPE/HELLP among both singleton and twin pregnancies. However, the adjusted associations between BMI, IVF, prior abortions, and SPE/HELLP differed by plurality (interaction p ‐values 0.002, < 0.0001, and 0.04, respectively). IVF was associated with increased odds of SPE/HELLP in singleton pregnancies (adjusted odds ratio (aOR) 1.93; 95% CI 1.64–2.27) but not in twins (aOR 0.85; CI 0.65–1.11). Similarly, overweight BMI was associated with elevated odds in singleton pregnancies (aOR 1.47; CI 1.32–1.64) but not in twins (aOR 0.86; CI 0.59–1.25), as was obese BMI (singleton aOR 1.88; CI 1.67–2.12; twin aOR 0.80; CI 0.51–1.24). Conversely, a history of prior abortions was associated with decreased odds in twin pregnancies (aOR 0.70; CI 0.54–0.92) but not singleton pregnancies (aOR 0.95; CI 0.88–1.04). Conclusions High BMI and IVF are associated with elevated risk of SPE/HELLP syndrome in singleton pregnancies, but not in twin pregnancies. This study provides insights regarding SPE/HELLP syndrome among singleton and twin pregnancies, and useful information for pre‐pregnancy counselling.