Association of Maternal Mild Hypothyroidism in the First and Third Trimesters with Obstetric and Perinatal Outcomes: A Prospective Cohort Study.

Background: Mild hypothyroidism, including subclinical hypothyroidism (SCH) and isolated maternal hypothyroxinemia (IMH), is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy.

Objective: To evaluate the impact of SCH and IMH in the first and third trimesters, respectively, on obstetric and perinatal outcomes.

Study design: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai. 52,027 pregnant women who underwent the first-trimester antenatal screening at IPMCH were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal SCH and IMH in the first trimester on pregnancy outcomes, participants were divided into three groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n= 33,130), first-trimester SCH group (n= 884), and first-trimester IMH group (n= 846). Then, to evaluate the impact of maternal SCH and IMH in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into three groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n= 30,776), third-trimester SCH group (n= 562), and third-trimester IMH group (n= 578). Obstetric and perinatal outcomes, including preterm birth (PTB), preeclampsia, gestational hypertension, gestational diabetes mellitus (GDM), large for gestational age (LGA), small for gestational age, macrosomia, cesarean section, and fetal demise were measured and compared between those in either SCH/IMH group and euthyroid group. Binary logistic regression was used to assess the association of SCH or IMH with these outcomes.

Results: 34,860 pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal SCH in the first trimester was linked to a lower risk of GDM (aOR 0.64, 95% CI 0.50-0.82) compared with the euthyroid group. However, third-trimester SCH is associated with heightened rates of PTB (aOR 1.56, 95%CI 1.10-2.20), preeclampsia (aOR 2.23, 95%CI 1.44-3.45), and fetal demise (aOR 7.00, 95%CI 2.07-23.66) compared with the euthyroid group. IMH in the first trimester increased risks of preeclampsia (aOR 2.14, 95% CI 1.53-3.02), GDM (aOR 1.45, 95%CI 1.21-1.73), LGA (aOR 1.64, 95%CI 1.41-1.91), macrosomia (aOR 1.85, 95%CI 1.49-2.31) and cesarean section (aOR 1.35, 95%CI 1.06-1.74), while IMH in the third trimester increased risks of preeclampsia (aOR 2.85, 95%CI 1.97-4.12), LGA (aOR 1.49, 95%CI 1.23-1.81) and macrosomia (aOR 1.60, 95%CI 1.20-2.13) compared with the euthyroid group.

Conclusion: This study indicates that while first-trimester SCH did not elevate the risk for adverse pregnancy outcomes, third-trimester SCH was linked to several adverse pregnancy outcomes. IMH in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.