Gestational Exposure to Endocrine-Disrupting Chemicals and Small Vulnerable Newborns: A Systematic Review and Meta-Analysis

Abstract

Endocrine-disrupting chemicals (EDCs) have been implicated in adverse birth outcomes, yet epidemiological findings remain inconsistent. We conducted a systematic review and meta-analysis to evaluate associations between gestational EDC exposure and small vulnerable newborns (SVNs), including preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). PubMed, Web of Science, and Embase were searched from inception to January 5, 2026. A total of 106 observational studies involving 98,133 births from 31 countries were included. Higher prenatal exposure to several per- and polyfluoroalkyl substances (PFAS), including perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), was associated with an increased risk of PTB, while PFOS was also associated with LBW. Perfluorooctanoic acid (PFOA), PFNA, PFDA, and perfluorohexanesulfonic acid (PFHxS) were positively associated with SGA. Among other EDCs, higher exposure to ∑DEHP, mono-2-cyclohexyl phthalate (MCPP), mono(2-ethylhexyl) phthalate (MECPP), monoisobutyl phthalate (MiBP), and bisphenol A (BPA) was associated with increased PTB risk. Stratified analyses suggested stronger associations in Asian populations, pregnancies with female fetuses, and countries without or with partial folic acid fortification. These findings indicate that prenatal exposure to PFAS and phthalates may increase the risk of SVNs, particularly PTB, and that population characteristics may modify these associations.