Thyroid autoimmunity and adverse pregnancy outcomes: A multiple center retrospective study

Abstract

Background: The relationship between thyroid autoimmunity (TAI) and adverse pregnancy outcomes is disputable, and their dose-dependent association have not been fully clarified.

Objective: To investigate the association and dose-dependent effect of TAI with multiple maternal and fetal-neonatal complications.

Methods: This study is a multi-center retrospective cohort study based on singleton pregnancies of three medical college hospitals from July 2013 to October 2021. The evolution of thyroid function parameters in TAI and not TAI women were described, throughout pregnancy. The prevalences of maternal and fetal-neonatal complications were compared between the TAI and control group. Logistic regression was performed to study the risk effects and dose-dependent effects of thyroid autoantibodies on pregnancy complications, with adjustment of maternal age, BMI, gravidity, TSH concentrations, FT4 concentrations and history of infertility.

Results: A total of 27408 participants were included in final analysis, with 5342 (19.49%) in the TAI group and 22066 (80.51%) in control group. TSH concentrations was higher in TAI women in baseline and remain higher before the third trimester. Positive thyroid autoantibodies were independently associated with higher risk of pregnancy-induced hypertension (OR: 1.215, 95%CI: 1.026-1.439), gestational diabetes mellitus (OR: 1.088, 95%CI: 1.001-1.183), and neonatal admission to NICU (OR: 1.084, 95%CI: 1.004-1.171). Quantitative analysis showed that increasing TPOAb concentration was correlated with higher probability of pregnancy-induced hypertension, and increasing TGAb concentration was positively correlated with pregnancy-induced hypertension, small for gestational age and NICU admission. Both TPOAb and TGAb concentration were negatively associated with neonatal birthweight.

Conclusion: Thyroid autoimmunity is independently associated with pregnancy-induced hypertension, gestational diabetes mellitus, neonatal lower birthweight and admission to NICU. Dose-dependent association were found between TPOAb and pregnancy-induced hypertension, and between TGAb and pregnancy-induced hypertension, small for gestational age and NICU admission.

Keywords: birth weight; dose dependent effect; gestational diabetes mellitus; maternal and fetal outcomes; pregnancy-induced hypertension; thyroid autoimmunity.

Figure 1

Flow chart of research population selection.

Figure 2

Evolution of maternal thyroid parameters during pregnancy. (A) Variation of TSH concentrations (lines) and sample size (bars) in each gestational month (the first and second bars represent 6-12 months and 0-6 months before pregnancy). (B) Variation of Free T4 concentrations (lines) and sample size (bars) in each gestational month (the first and second bars represent 6-12 months and 0-6 months before pregnancy). (C) Variation of Free T3 concentrations (lines) and sample size (bars) in each gestational month (the first and second bars represent 6-12 months and 0-6 months before pregnancy). (D) Evolution of TSH, Free T4 and Free T3 level by TPOAb concentrations (related to the concentrations of TSH, Free T4 and Free T3 in cases with TPOAb concentration lower or equal to the 85 percentile).

Figure 3

Quantitative association of thyroid autoimmunity and pregnant complications. ^aAdjusted for Age, BMI, Gravidity, TSH level, Free T4 level, and history of infertility. ^bAdjusted for Age, BMI, Gravidity, TSH level, Free T4 level, history of infertility, and family history of hypertension. ^cAdjusted for Age, BMI, Gravidity, TSH level, Free T4 level, history of infertility, and family history of diabetes. ^d Adjusted for Age, BMI, Gravidity, TSH level, Free T4 level, history of infertility, and history of recurrent miscarriage.

Figure 4

Quantitative Association of Birthweight and Thyroid Autoantibody. (A) Birthweight decreased with increasing TPOAb concentrations (percentiles). (B) Birthweight decreased with increasing TGAb concentrations (percentiles).