Maternal TPO-Ab status modulates associations between gestational thyroid hormones and neonatal TSH in 10,154 Chinese mother–newborn pairs

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.