Causal association between pregnancy disorders and neonatal jaundice: a two-sample Mendelian randomization study

Background: Some studies have suggested that complications during pregnancy, such as preeclampsia, leiomyoma during pregnancy, oxytocin induction, and mode of delivery, may be risk factors for neonatal jaundice. Herein, we applied Mendelian randomization (MR) analysis to investigate a causal association between pregnancy disorders and neonatal jaundice.Methods: Data related to neonatal jaundice and pregnancy disorders (including pre-eclampsia or eclampsia, gestational diabetes, and gestational edema) were sourced from the FinnGen Consortium and Integrated Epidemiology Unit (IEU) databases. Inverse-variance weighted (IVW) was used as a main approach for data analysis, while MR-Egger, weighted median (WM), and weighted mode methods were used to validate the robustness of the results. MR-Egger regression method was applied to explore the presence of horizontal pleiotropy. MR pleiotropy residual sum and outlier (MR-PRESSO) method was used to detect potential outliers. Cochran's Q test was used to assess heterogeneity among instrumental variables (IVs); leave-one-out (LOO) analyses were used to evaluate the presence of predominant IVs. Results: The IVW approach showed that pre-eclampsia or eclampsia {odds ratio (OR) [95% confidence interval (CI)]: 0.86 (0.36-2.07), P=0.73}, gestational edema and proteinuria [OR (95% CI): 1.04 (0.62-1.74), P=0.87], and gestational diabetes mellitus [OR (95% CI): 0.95 (0.60-1.49), P=0.81] were not associated with neonatal jaundice. The MR-Egger regression results showed that horizontal pleiotropy did not affect the relationship between exposure factors and outcomes. Also, no heterogeneity was observed. The MR-PRESSO analysis showed no outliers, confirming that these data were robust.Conclusions: Our data suggested no genetic causal association between pre-eclampsia or eclampsia, gestational edema, proteinuria, gestational diabetes mellitus, and neonatal jaundice. However, further research is needed to determine if these results apply to other races