Maternal determinants of craniosynostosis: Insights from a systematic review and meta-analysis

Abstract

Craniosynostosis, a congenital condition caused by premature fusion of cranial sutures, poses serious challenges to neonatal health and development, and maternal factors have been increasingly recognized as contributors to its etiology. The aim of this study was to evaluate maternal determinants of craniosynostosis and quantify their associations through a systematic review and meta-analysis. A comprehensive search of PubMed, Scopus, and Google Scholar was conducted to identify observational studies reporting maternal risk factors. Eligible studies were assessed for quality, and meta-analyses were performed using random-effects models to calculate pooled odds ratios (ORs) and assess heterogeneity. Six studies met the inclusion criteria. Advanced maternal age (≥30 years) was associated with a 53% higher risk of craniosynostosis (OR: 1.53, 95%CI: 1.25–1.87), while maternal obesity (BMI ≥30 kg/m²) was linked to a 42% higher risk (OR: 1.42; 95%CI: 1.18–1.71). Ethnic disparities were observed, with non-Hispanic Black (OR: 0.73; 95%CI: 0.58–0.92) and Hispanic mothers (OR: 0.81; 95%CI: 0.65–0.99) having lower risks compared with non-Hispanic White mothers. Heterogeneity was moderate for maternal age (I²= 48%) and low for BMI (I²= 22%). Overall, advanced maternal age and obesity emerged as consistent maternal risk factors for craniosynostosis, while ethnic differences suggest potential protective influences in certain populations. These findings highlight the importance of targeted preconception counseling, maternal health interventions, and further research to elucidate underlying mechanisms and guide preventive strategies.