OBJECTIVE: To summarize the role of antenatal risk factors for infant cerebral palsy (CP) by un umbrella review. DATA SOURCES: Pubmed, Cochrane list of trials, Medline and Google Scholar were searched for meta-analyses and systematic reviews, published between September 2009 and August 2025. STUDY ELIGIBILITY CRITERIA: In all the studies included, the diagnosis of CP was made according to standard definitions after a minimum of two-year follow-up (PROSPERO N.XXXXXXXXXX). STUDY APPRAISAL AND SYNTHESIS METHOD: Results from primary studies were re-analyzed with dedicated software (Metaumbrella). The AMSTAR 2 checklist was used to determine the level of confidence in the meta-analyses' findings. Evidence strength was stratified into five categories: convincing, highly suggestive, suggestive, weak, and non-significant. RESULTS: A total of 35 meta-analyses, 16 systematic reviews, and 261 primary investigations, predominantly from developed countries, were included. The analysis assessed 54 antenatal, pregnancy, and delivery-related risk and protective factors, identifying 43 significantly associated with infant CP. Key antenatal risk factors included pre-pregnancy obesity (eOR=1.36, 95% CI=1.28-1.45, convincing evidence), smoking during pregnancy (eOR=1.32, 95% CI=1.22-1.44, convincing evidence), and singleton pregnancies from assisted reproductive technology (suggestive evidence). Among delivery-related factors, prematurity was the strongest risk, with odds inversely correlated with gestational age. Infants born before 32 weeks had the highest risk (eOR=40.8, 95% CI=32.3-51.6, highly suggestive evidence). Risk progressively decreased for infants born at 32-33 weeks (eOR=14), 34-36 weeks (eOR=3.49), and 37-38 weeks (eOR=1.62). Additional significant risks included a male fetus, maternal age >39 or <20, preexisting diabetes, alcohol exposure, low socioeconomic status, consanguinity, infections, twin pregnancies, preeclampsia, very-low birthweight, congenital anomalies, emergency cesarean section, operative vaginal delivery, and abnormal placental pathology. Protective factors included a single course of corticosteroids in preterm pregnancies (eOR=0.70, 95% CI=0.61-0.79, convincing evidence) and magnesium sulfate prophylaxis in very preterm deliveries (eOR=0.56, 95% CI=0.40-0.78, weak evidence). Indicated preterm delivery, rather than spontaneous, was also associated with reduced CP risk. CONCLUSIONS: This analysis highlights the critical role of modifiable factors such as maternal obesity, smoking, alcohol use, and perinatal care in reducing the prevalence of CP. Prematurity remains a predominant risk, emphasizing the need for targeted prevention strategies.
Arsenio et al. (Fri,) studied this question.