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

Area of Science:

• Perinatal Medicine
• Neonatology
• Genetic Epidemiology

Background:

• Pregnancy complications such as preeclampsia, leiomyoma, oxytocin induction, and delivery mode have been implicated as potential risk factors for neonatal jaundice.
• Investigating causal links is crucial for understanding and potentially preventing neonatal jaundice.

Purpose of the Study:

• To investigate the potential causal association between specific pregnancy disorders and neonatal jaundice using Mendelian randomization (MR).
• To determine if genetic factors underlying pregnancy complications influence the risk of neonatal jaundice.

Main Methods:

• Utilized large-scale genetic data from the FinnGen Consortium and Integrated Epidemiology Unit (IEU) databases.
• Applied inverse-variance weighted (IVW) as the primary MR analysis method, with MR-Egger, weighted median, and weighted mode for robustness checks.
• Assessed for horizontal pleiotropy using MR-Egger regression and MR-PRESSO, and evaluated heterogeneity with Cochran's Q test and leave-one-out analyses.

Main Results:

• No statistically significant causal association was found between pre-eclampsia or eclampsia, gestational edema with proteinuria, or gestational diabetes mellitus and neonatal jaundice.
• Robustness checks confirmed the absence of significant horizontal pleiotropy or outliers, indicating reliable results.
• No significant heterogeneity was observed among the instrumental variables.

Conclusions:

• The study found no evidence of a genetic causal relationship between key pregnancy disorders and neonatal jaundice.
• These findings suggest that common pregnancy complications do not directly cause neonatal jaundice through genetic pathways.
• Further research is recommended to validate these findings across diverse populations and ethnicities.