The Quartile Levels of Thyroid-stimulating Hormone at Newborn Screening Stratified Risks of Neurodevelopmental Impairment in Extremely Preterm Infants: A Population Cohort Study

Background: To evaluate whether thyroid-stimulating hormone (TSH) measured during newborn screening (NBS) at birth and at discharge can be surrogate markers for neurodevelopmental impairment (NDI) in extremely preterm infants. Methods: The population cohort enrolled infants born <29 weeks’ gestation in 2008–2020 in southern Taiwan. Infants with a maternal history of thyroid disorders and infants who required thyroxine supplementation during hospitalization were excluded. TSH levels measured during NBS at birth and at term-equivalent age (TEA)/discharge were respectively categorized into the lowest quartile, the interquartile range, and the highest quartile, which were correlated to NDI outcomes. Results: Among 392 patients with paired TSH data, 358 (91%) were prospectively followed until a corrected age of 24 months. At birth, infants with lowest-quartile TSH had higher NDI risks (odds ratio [OR] 2.3; 95% confidence interval [CI], 1.3–4.1, P = 0.004) compared to infants with interquartile-range TSH. Conversely, by TEA/discharge, infants with highest-quartile TSH had increased NDI (OR 1.9; 95% CI, 1.0–3.4, P = 0.03). By paired TSH categories, infants persistently in the lowest TSH quartile (48%; aOR 4.4; 95% CI, 1.4–14.5, P = 0.01) and those with a shift from interquartile range to the highest quartile (32%; aOR 2.7; 95% CI, 1.0–7.4, P = 0.046) had increased NDI risks compared with the reference with consistent interquartile-range TSH. Conclusion: Extremely preterm infants persistently in the lowest-quartile TSH level at birth and at discharge had the highest NDI risk. TSH quartile levels measured during NBS may serve as a population surrogate biomarker for assessing NDI risks in infants born extremely preterm.