Maternal TPO-Ab status modulates associations between gestational thyroid hormones and neonatal TSH in 10,154 Chinese
Huihui Wang1, Sijie Xi2, Xusheng Chen2
1Department of Obstetrics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
Background:
Evidence on the maternal-fetal thyroid hormone (TH) axis is limited, especially regarding how maternal thyroid peroxidase antibody (TPO-Ab) status affects the link between gestational thyroid function and neonatal thyroid-stimulating hormone (TSH).
Objectives:
This study explored how maternal TH in late pregnancy influences neonatal TSH and assessed whether TPO-Ab modifies this relationship.
Design:
This retrospective cohort study was conducted at a tertiary specialized hospital.
Methods:
A total of 10,154 eligible mother-newborn pairs were analyzed. Maternal TSH, free thyroxine (FT4), free triiodothyronine (FT3), and TPO-Ab were measured before birth; neonatal TSH was measured 3-7 days postbirth. Mothers were classified as TPO-Ab positive (>34 IU/mL) or negative.
Results:
Maternal TPO-Ab positivity prevalence was 5.5%, while congenital hypothyroidism (CH) screening positivity (TSH ⩾10 mIU/L) occurred in 0.87% of neonates. Among TPO-Ab-negative mothers, maternal TSH positively correlated with elevated neonatal TSH (adjusted β: 0.14, 95% confidence interval (CI): 0.10-0.17, p < 0.001) and CH risk (adjusted odds ratio: 1.21, 95% CI: 1.09-1.33, p < 0.001). A nonlinear dose-response relationship revealed a threshold at 4.85 mIU/L: below this value, neonatal TSH increased sharply with maternal TSH (β: 0.21, 95% CI: 0.16-0.26, p < 0.001). No significant associations existed in TPO-Ab-positive mothers. TPO-Ab status reversed the neonatal TSH-maternal FT3/FT4 ratio relationship: negative correlation in TPO-Ab-negative mothers (β: -1.78, 95% CI: -2.70 to -0.87, p < 0.001) versus positive correlation in TPO-Ab-positive mothers (β: 11.31, 95% CI: 2.03-20.58, p = 0.017).
Conclusion:
Maternal TSH correlates with neonatal TSH in TPO-Ab-negative pregnancies with a threshold at 4.85 mIU/L. TPO-Ab abolishes this association and reverses the FT3/FT4 ratio-neonatal TSH relationship, establishing TPO-Ab status as a critical modifier of maternal-fetal thyroid interactions. These findings support integrating TPO-Ab screening into prenatal thyroid management to optimize neonatal outcomes. However, the observational design limits causal inference, and further prospective studies are warranted.
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