Maternal smoking during pregnancy, other reproductive factors, and neonatal jaundice: A two-sample Mendelian randomization study.

INTRODUCTION: Neonatal jaundice is a common condition affecting 60% of term and 80% of preterm infants. This study aimed to explore the genetic prediction of associations between reproductive factors, including age at menarche, age at first birth, age at first intercourse, hypertension during pregnancy, gestational diabetes, and smoking during pregnancy, and neonatal jaundice using two-sample Mendelian randomization (MR).

METHODS: A two-sample MR analysis was conducted utilizing genome-wide association studies (GWAS) summary statistics for six reproductive factors and neonatal jaundice from public databases, with data derived from individuals of European ancestry. The primary analysis employed the inverse variance weighted (IVW) method, while supplementary analyses included MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses were assessed with Cochran's Q test, MR-Egger, MR-PRESSO test, and leave-one-out methods. Statistical power was calculated using the mRnd tool.

RESULTS: Our findings indicated that genetically maternal smoking during pregnancy was associated with neonatal jaundice (OR=8.5227; 95% CI: 1.9246-37.7403, p=0.0048), with adequate statistical power (84.85%). No effect was observed for other reproductive factors on neonatal jaundice (All p>0.05), including age at menarche, age at first birth, age at first intercourse, hypertension during pregnancy, and gestational diabetes. Statistical power for these analyses was limited (<10%). In addition, sensitivity analyses confirmed these findings, indicating robustness against potential pleiotropy and heterogeneity.

CONCLUSIONS: These results suggest that maternal smoking during pregnancy is associated with an increased risk of neonatal jaundice. Further research on the underlying biological mechanisms may help to better understand this association and its potential relevance for clinical practice.