Identifying the risk factors of autism spectrum disorders in infants born preterm: a systematic review and...

Compared with infants born at term, infants born preterm are more likely to develop autism spectrum disorder (ASD), but specific risk factors remain uncertain. To identify possible risk factors associated with ASD development in infants born preterm. We systematically searched PubMed, Embase, Web of Science, CINAHL and Scopus to May 2025 for observational studies reporting ASD in infants born preterm. Meta-analyses used RevMan 5.4 and Stata 14.0. We assessed certainty of the evidence using the GRADE approach. A total of 45 studies were included in the systematic review, of which 40 were included in the meta-analyses. Twenty-two potential risk factors were identified. Prenatal factors included male, small for gestational age (SGA), lower birth weight, lower gestational age, low maternal education, ethnic minorities, antepartum hemorrhage (APH), and multiple births. Postnatal factors included severe cranial ultrasound abnormality, cerebral palsy (CP), severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), more days on mechanical ventilation, necrotizing enterocolitis (NEC), sepsis, longer neonatal intensive care unit (NICU) stay, delivery room resuscitation, longer duration of oxygen therapy, postnatal steroid administration, inotropic support, small head circumference (HC) at birth, and lack of breastfeeding. Overall, the certainty of evidence was low or very low, indicating that the associations between these risk factors and ASD in infants born preterm are highly uncertain. Our findings suggest that these 22 prenatal and postnatal factors may be associated with an increased risk of ASD in infants born preterm; however, due to low or very low certainty of evidence, the conclusions remain highly uncertain. Further high-quality prospective studies are needed to confirm these associations and to inform risk stratification and targeted preventive strategies.