Abstract

Introduction: Maternal thyroid hormones (TH) are essential for fetal growth and development. While prior studies have examined associations of TH with birthweight (BW), data on other neonatal anthropometric measures are scarce. Here we aimed to examine relations between TH and its trajectory across pregnancy with neonatal anthropometrics in a multi-racial pregnancy cohort. Hypothesis: We hypothesized that distinct TH trajectories across gestation would explain differences in neonatal anthropometrics including BW, length and sum of skinfolds (SSF). Methods: We used longitudinal data from 321 women who were included in a gestational diabetes (GDM) case-control study nested within the NICHD Fetal Growth Studies-Singletons Cohort (n=2802). Plasma free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were measured, and fT3/fT4 ratio was derived, using blood samples collected at gestational weeks (GW) 10-14, 15-26, 23-31 and 33-39. TH trajectories were identified using a latent class trajectory approach. BW was abstracted from medical records. Neonatal length and SSF were measured. To examine associations between TH levels and neonatal outcomes, we used weighted linear regression models, adjusted for maternal age, race/ethnicity, GW at blood collection, pre-pregnancy BMI, education, parity, infant sex, GDM diagnosis (33-39 GW only) and number of days post-delivery (length and SSF only). Results: Overall, neonates of women in the highest fT3 tertile at 33-39 GW had marginally higher BW (β: 205.5 g, 95% CI -23.4, 434.4) and BW z-score (β: 0.4, 95% CI 0.0, 0.8) than neonates of women in the lowest tertile. Significant interactions were observed by infant sex for associations of fT4 and BW, BW z-score and neonatal length (all p for interactions <0.05). Specifically, female neonates of women in the highest fT4 tertile had lower BW, BW z-score and length than those in the lowest tertile at 15-26 (β BW -416.3 g, 95% CI -753.7, -79.0; β BW zscore -0.5, 95% CI -0.9, -0.1; β length -1.5 cm, 95% CI -2.8, -0.1, respectively) and 23-31 GW (β BW -357.0 g, 95% CI -635.6, -78.4; β BW zscore -0.7, 95% CI -1.3, -0.1; β length -1.8 cm, 95% CI -3.3, -0.2, respectively). Across gestation, a low fT3 trajectory (class size 5.5%) was associated with lower neonatal SSF (β: -3.2 mm, 95% CI -6.0, -0.5) than an intermediate/referent trajectory (60.1%). A high fT3/fT4 ratio trajectory (16.2%) was associated with higher BW (β: 300.5 g, 95% CI 41.7, 559.4), BW z-score (β: 0.6, 95% CI 0.3, 0.8), and neonatal SSF (β: 3.3 mm, 95% CI 0.7, 5.9) than an intermediate/referent trajectory (44.3%). Conclusions: Our study suggests that both overall TH trajectory across gestation and TH levels at specific timepoints in pregnancy may be related to neonatal anthropometrics, with associations varying by infant sex. These novel data support the significance of monitoring thyroid hormones longitudinally in pregnancy.

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