Thyroid function changes in pregnant women with thyroid cancer and their association with adverse fetal outcomes: a parallel controlled study

BACKGROUND: The effects of thyroid hormone replacement or suppression therapy in women with thyroid cancer on thyroid function during pregnancy and subsequent adverse fetal outcomes are still largely unknown. To compare thyroid function at 8 weeks of gestation and its changes during pregnancy between the survivors and controls, and to assess the association of these differences with adverse fetal outcomes. METHODS: This was a retrospective cohort-based parallel control study. A total of 140 survivors and 280 controls delivery time-matched controls were extracted from 46,610 singleton pregnant women who received prenatal examinations in a second-level specialized hospital between January 2019 and March 2024. The primary outcomes were birth defects, small for gestational age (SGA, defined as birth weight < 10th percentile by gestational week), preterm birth (< 37 weeks), and neonatal asphyxia (defined as fetuses with a 1 min-Apgar score of < 7). Apgar scores at 1 and 5 min and umbilical arterial blood gas (ABG) indexes were surrogate indicators of neonatal asphyxia. RESULTS: Compared to the control group, FT3 was lower in the survivors, while FT4 was higher. Change of FT3 between 8 and 16 weeks of gestation in survivors was significantly smaller than that in the controls (-0.08 vs. -0.30, P < 0.005). The survivors had an insignificant association with SGA/preterm birth (adjusted OR 2.06, 0.68-6.23, P = 0.20), a slightly higher risk of fetal asphyxia (Peto OR, 6.49; 95% CI: 0.81-52.0; P = 0.078), and a lower 1 min Apgar score (β, -0.10; 95% CI: -0.16 to -0.03;P = 0.004). Change in FT3 between 8 and 16 weeks was associated with SGA/preterm birth (adjusted OR, 4.42, 95%CI: 1.32-14.84, P = 0.016). FT3 at 8 weeks of gestation and its changes between 16 and 32 weeks of gestation were negatively correlated with the umbilical ABG index, with both β of -0.02(p = 0.015 and 0.019, respectively). CONCLUSIONS: This study found differences in FT3 and FT4 levels and their changes during pregnancy between the survivors and controls. These differences, especially the changes in FT3 during pregnancy, might suggest a potential biological link, though further studies are needed to establish causality.