Background: The association between isolated maternal hypothyroxinemia (IMH) during pregnancy and preterm birth (PTB), especially for subtypes of PTB, is unclear. This study aimed at determining the association between IMH diagnosed in early pregnancy and PTB, with further investigation into various subtypes of PTB. Methods: This study included 41,911 pregnant women (963 with IMH and 40,948 euthyroid women) who underwent first-trimester prenatal screening at the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai, China between January 2013 and December 2016. PTB was defined as birth before 37 weeks of gestation. PTB was further classified into three clinically relevant groups to investigate the clinical heterogeneity of PTB: (a) preterm birth with premature rupture of membranes (PROM-PTB); (b) spontaneous preterm birth with intact membranes (S-PTB); and (c) medically-induced preterm birth (MI-PTB). The overall and sex-specific effect of IMH on PTB and various subtypes of PTB were estimated by using logistic regression in crude and adjusted models. Results: Pregnant women with IMH had an increased risk of PTB (odds ratio [OR]: 1.32 [95% confidence interval; CI: 1.02-1.70], p = 0.03) compared with women with euthyroid function. The increased risk of PTB is mainly driven by S-PTB (OR: 1.57 [CI: 1.11-2.24], p = 0.01), while women with early pregnancy IMH had no statistically significant increased risk of PROM-PTB and MI-PTB. The effect of IMH on PTB was modified by fetal sex (p-values for interaction = 0.04). More prominent effects were observed in women carrying a female fetus, while no statistically significant effects were found in women carrying a male fetus. Conclusions: This study revealed that pregnant women with IMH in early pregnancy have a higher risk of PTB compared with euthyroid women. The effect of IMH on PTB is mainly driven by S-PTB and is modified by fetal sex.
Keywords: fetus sex; isolated hypothyroxinemia; pregnancy; preterm birth; thyroid disease.