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.