Longitudinal Trajectories of Gestational Thyroid Function: A New Approach to Better Understand Changes in Thyroid Function

Abstract

Context Most studies of thyroid function changes during pregnancy use a cross-sectional design comparing means between groups rather than similarities within groups. Objective Latent class growth analysis (LCGA) is a novel approach to investigate longitudinal changes that provide dynamic understanding of the relationship between thyroid status and advancing pregnancy. Design Prospective observational study with repeated assessments. Setting General community. Patients Eleven hundred healthy women were included at 12 weeks’ gestation. Main Outcome Measures The existence of both free T4 (fT4) and TSH trajectories throughout pregnancy determined by LCGA. Results LCGA revealed three trajectory classes. Class 1 (n = 1019; 92.4%), a low increasing TSH reference group, had a gradual increase in TSH throughout gestation (from 1.1 to 1.3 IU/L). Class 2 (n = 30; 2.8%), a high increasing TSH group, displayed the largest increase in TSH (from 1.9 to 3.3 IU/L). Class 3 (n = 51; 4.6%), a decreasing TSH group, had the largest fall in TSH (from 3.2 to 2.4 IU/L). Subclinical hypothyroidism at 12 weeks occurred in up to 60% of class 3 women and was accompanied by elevated thyroid peroxidase antibodies (TPO-Ab) titers (50%) and a parental history of thyroid dysfunction (23%). In class 2, 70% of women were nulliparous compared with 46% in class 1 and 49% in class 3. Conclusions LCGA revealed distinct trajectories of longitudinal changes in fT4 and TSH levels during pregnancy in 7.4% of women. These trajectories were correlated with parity and TPO-Ab status and followed patterns that might reflect differences in pregnancy-specific immune tolerance between nulliparous and multiparous women.