The Clinical Utility of Individual Iodine Status Measures in Infants With Abnormal Thyroid Function: A Systematic Review

OBJECTIVE: To evaluate methods used to assess individual iodine status in infants under 2 years of age and to examine their clinical utility in relation to thyroid dysfunction across different clinical contexts. DESIGN: The protocol was registered on PROSPERO and followed PRISMA guidelines. Five databases and grey literature were searched, with backward and forward citation searching. Studies were independently screened, extracted, and appraised by two reviewers, with disagreements resolved by a third reviewer. RESULTS: Thirty-one studies met inclusion criteria. Urinary iodine concentration (UIC) was the most used method (n = 26), with significant heterogeneity. UIC and breast milk iodine concentration (BMIC) reflected iodine excess, including in cases of congenital hypothyroidism (CH) and were associated with abnormal thyroid function tests in known exposure scenarios in some studies. Prematurity was a key modifier of iodine handling and thyroid response. In CH due to iodine deficiency, maternal UIC was a better indicator than infant UIC. Measurement timing, infant age and health status were significant confounders. Thyroglobulin (Tg) showed associations with iodine exposure, serum iodine, and thyroid dysfunction, but its relationship with infant UIC remains unclear. CONCLUSIONS: No single method reliably assesses iodine status in individual infants. Interpretation of iodine biomarkers should consider clinical context, gestational age, timing of measurement, and exposure history. A multi-modal, context-specific approach integrating iodine measures and thyroid function testing is recommended. Longitudinal studies are needed to establish age- and gestation-specific reference ranges and to refine clinical interpretation of assessment methods, including novel markers of iodine status.