Mendelian randomization study: investigating the causal impact of Covid-19 on adverse pregnancy outcomes

Due to limitations in observational studies, the link between COVID-19 and adverse pregnancy outcomes (APOs) remains inconclusive. This study uses two-sample Mendelian randomization (MR) analyses to assess COVID-19's causal effects on APO traits.

We applied inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode to thoroughly evaluate the effects of COVID-19 infection, hospitalization, and critical status on eight APO traits.

Our findings indicate that COVID-19 infection is associated with a decreased risk of eclampsia (OR: 0.35, 95%CI [0.13, 0.94]; p = 0.033) and the number of spontaneous miscarriages (OR: 0.95, 95%CI [0.91, 0.99]; p = 0.014), and an increased risk of preterm labor and delivery (OR: 1.30, 95%CI [1.04, 1.63]; p = 0.019). Hospitalized COVID-19 is associated with pre-eclampsia (OR: 1.13, 95%CI [1.00, 1.28]; p = 0.040), pre-eclampsia or eclampsia (OR: 1.14, 95%CI [1.01, 1.28]; p = 0.029), pregnancy hypertension (OR: 1.09, 95%CI [1.01, 1.18]; p = 0.021), hypertension complicating pregnancy, childbirth, and the puerperium (OR: 1.09, 95%CI [1.01, 1.18]; p = 0.021), and oedema, proteinuria, and hypertensive disorders in pregnancy, childbirth, and the puerperium (OR: 1.10, 95%CI [1.03, 1.19]; p = 0.005). Critical COVID-19 is a risk factor for pre-eclampsia or eclampsia (OR: 1.08, 95%CI [1.00, 1.17]; p = 0.044) and oedema, proteinuria, and hypertensive disorders in pregnancy, childbirth, and the puerperium (OR:1.05, 95%CI [1.00, 1.11]; p = 0.031).

Our study uncovered genetic evidence supporting COVID-19 as a causal risk factor for APOs, suggesting the importance of prioritizing therapeutic interventions for pregnant women infected with COVID-19 within society.