Associations of onset time, severity, and persistence of hypothyroxinemia with pregnancy outcomes: A retrospective study

Background Evidence regarding adverse pregnancy outcomes in pregnancies with hypothyroxinemia remains controversial, and the effect of onset time, severity, and persistence of hypothyroxinemia has not been thoroughly investigated. This study aims to evaluate the associations between hypothyroxinemia and adverse pregnancy outcomes with respect to the onset time, severity, and persistence of hypothyroxinemia. Methods This retrospective cohort study included 51, 305 singleton pregnancies who delivered at a tertiary hospital between January 2017 and December 2021. Thyroid function data and clinical information were obtained through digital medical records. Participants were categorized into euthyroid and hypothyroxinemia group according to free thyroxine (FT4) and thyrotropin (TSH) values in the first (gestational week 9-13) and third trimester (gestational week 32-36). Hypothyroxinemia was defined as FT4 < 10 ^th gestational age-specific percentile in combination with TSH level within the 10 ^th -90 ^th percentile. Pregnancy outcomes were compared between women with hypothyroxinemia and euthyroidism with respect to the onset time, severity, and persistence of hypothyroxinemia. The associations between hypothyroxinemia and adverse outcomes were assessed using binary logistic regression in crude and adjusted models. Results Compared with the euthyroid group, hypothyroxinemia in the first trimester was associated with higher risk of Cesarean delivery (adjusted odds ratio [aOR], 1.20, 95% confidence interval [CI]: 1.11-1.29), macrosomia (aOR, 1.25, 95%CI: 1.08-1.44), and gestational diabetes mellitus (GDM) (aOR, 1.49, 95%CI: 1.36-1.63), and the risk increased as FT4 levels decreasing. Hypothyroxinemia in the third trimester was linked with heightened risk of Cesarean delivery (aOR, 1.52, 95%CI: 1.40-1.66), macrosomia (aOR, 1.44, 95%CI: 1.27-1.73), pre-eclampsia (aOR, 1.72, 95%CI: 1.38-2.14), and gestational hypertension (aOR, 1.44, 95%CI: 1.18-1.76), and the risk was negatively correlated with FT4 levels. Persistent hypothyroxinemia was linked with an increased risk of Cesarean delivery (aOR, 1.50, 95%CI: 1.28-1.76) and GDM (aOR, 1.45, 95%CI: 1.19-1.76).  Conclusion This study revealed that both the first- and third-trimester hypothyroxinemia were associated with increased risk of Cesarean delivery and macrosomia, and the risk increased as the FT4 levels decreasing. However, the relations of hypothyroxinemia with pre-eclampsia, gestational hypertension, and GDM varied by the gestational age when hypothyroxinemia was diagnosed and the persistence of hypothyroxinemia.