Prenatal and postnatal exposure to endocrine-disrupting chemicals: Implications for extremely preterm infants,...

Preterm birth affects approximately 13.4-15 million infants annually and remains a leading cause of neonatal morbidity and mortality. Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) may represent an important and underrecognized contributor to adverse outcomes in extremely preterm infants (<28 weeks' gestation). These infants experience a "double-hit" exposure-prenatally via placental transfer and postnatally through intensive care interventions-during critical windows of development. EDCs, including phthalates, bisphenols, parabens, persistent organic pollutants, per- and polyfluoroalkyl substances, heavy metals, and pesticides, can interfere with endocrine signaling through receptor-mediated pathways, disruption of hormone synthesis and metabolism, epigenetic modifications, oxidative stress, and inflammation. These mechanisms are biologically plausible contributors to organ-specific vulnerability, potentially affecting respiratory, neurological, gastrointestinal, immune, and endocrine-metabolic systems. Epidemiological studies consistently associate prenatal EDC exposure-particularly phthalates-with preterm birth, although effect sizes are generally modest and causality remains difficult to establish. Evidence linking EDC exposure to specific neonatal morbidities in extremely preterm infants is more limited and often indirect, relying on mechanistic and experimental data. In neonatal intensive care units, medical devices represent a major source of exposure, with phthalate biomarker levels reported to exceed safety thresholds in some cohorts. Despite regulatory efforts, exposure persists, and the safety of alternative plasticizers remains incompletely characterized. Exposure assessment is challenged by short chemical half-lives, variability across biological matrices, mixture effects, and the absence of neonatal-specific reference values. EDC exposure represents a potentially modifiable risk factor. Reducing exposure may have important clinical and public health implications. Further longitudinal and mechanistic studies are needed.