Mendelian randomization reveals systemic lupus erythematosus and rheumatoid arthritis and risk of adverse pregnancy outcomes

Background: The effect of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) on adverse pregnancy outcomes is a controversial topic. This study aimed to use Mendelian randomization (MR) analysis to assess the causal relationship between SLE, RA and adverse pregnancy outcomes. Methods: Genetic variants for SLE and RA, as well as adverse pregnancy outcomes, were derived from pooled statistics from large public genome-wide association studies. Several methods, such as inverse variance weighting (IVW), MR-Egger, weighted median and MR-Pleiotropic Residuals Sum and Outliers, were employed to estimate two-sample causality. Results: Genetic prediction of SLE was associated with higher odds of preterm labour [odds ratio (OR) 1.03, 95 % confidence interval (CI) 1.01-1.05; p = 0.008]. RA was associated with higher odds of preterm labour (OR 1.03, 95 % CI 1.01-1.06; p = 0.009), pre-eclampsia or eclampsia (OR 1.04, 95 % CI 1.01-1.07; p = 0.005), and poor fetal growth (OR 1.08, 95 % CI 1.04-1.12; p = 2.91 x 10- 5). The results of bidirectional MR analysis did not indicate that SLE was associated with spontaneous abortion, pre-eclampsia or eclampsia, preterm rupture of membranes, or poor fetal growth (p-value for IVW 0.13-0.97). Conclusions: This study found a genetic association between SLE and the risk of preterm labour, and highlights the importance of perinatal care and monitoring for patients with SLE. Furthermore, RA was found to be associated with a wide range of adverse outcomes, including preterm labour, pre-eclampsia or eclampsia, and poor fetal growth; as such, there is a need for more intensive therapeutic interventions and prenatal monitoring.