Late Age at First Birth is a Protective Factor for Preterm Labor and Delivery: The Evidence From the Genetic Study

The objective of this study was to investigate the genetic link between the age at first birth (AFB) and the occurrence of preterm labor and delivery, utilizing Mendelian randomization (MR) data alongside genomewide association analysis (GWAS). We obtained AFB-related GWAS summary data from the European Bioinformatics Institute database and preterm labor and delivery data was sourced from the FinnGen Consortium. The study considered AFB as exposure variables, with the incidence of preterm labor and delivery serving as the outcome variable. Several MR analysis methods, such as inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted mode were utilized. Besides MR-Egger intercepts, Cochrane's Q test evaluated heterogeneity in the MR data, while MR-PRESSO test checked for horizontal pleiotropy. To assess the association's sensitivity, A leave-one-out approach was utilized to evaluate the sensitivity of the association. The IVW analysis validated that AFB is an independent risk factor for preterm labor and delivery (<i>p</i> < .001). Horizontal pleiotropy was unlikely to bias causality (<i>p</i> > .05). The likelihood of horizontal pleiotropy affecting causality was low (<i>p</i> > .05), and there was no indication of heterogeneity among the genetic variants (<i>p</i> > .05). Ultimately, a leave-one-out analysis confirmed the stability and reliability of this correlation. Our research indicated that AFB is a protective factor for preterm labor and delivery. Further research is required to clarify the possible mechanisms.