Introduction: Cranial sutures are fibrous joints between skull bones that remain flexible during infancy, allowing for further brain growth and development. Craniosynostosis, a congenital abnormality involving premature closure of cranial sutures, leads to abnormal skull shape and may result in developmental delays, sensory deficits, and neurological or respiratory dysfunction if left untreated. The prevalence of craniosynostosis is 1 in 2000 to 2500 live births and is trending upwards, although its exact cause is unknown. This study aims to elucidate risk factors associated with craniosynostosis to better understand the disorder and identify potential preventative measures. Methods: A case-control study was designed to identify potential predisposing risk factors for developing craniosynostosis. An electronic medical records review was conducted at our University of Missouri Medical Center, a Level 1 Trauma and Regional Perinatal Center located in central Missouri, on those who received prenatal care and delivered at our facility between 6/1/22-11/1/24. Extracted data included maternal demographics, pregnancy and delivery course, perinatal ultrasound number and findings, neonatal demographics, type of craniosynostosis and course post-delivery. A 2:1 case to control methodology was utilized, with controls matched by date of birth. One male and one female infant delivered as close to the delivery time of the craniosynostosis case, with the same data extracted from our EMR, served as controls. Data were maintained in a de-identified secure RedCap databank. Comparisons between groups were made using Chi-square, Fisher’s exact testing, and Mann-Whitney U testing as appropriate. Results are presented as percent, or mean +/- standard deviation as appropriate, with odds ratios and 95% confidence intervals. A P < 0.05 was considered statistically significant. Statistical analysis was completed using VassarStats and SPSS. IRB approval was received prior to initiation of this study. Results: Forty-two patients were identified with non-syndromic craniosynostosis, indicating isolated cranial suture involvement. 38.1% involved the sagittal suture, 33.3% metopic suture, 31.0% coronal suture, and 4.8% lambdoid suture. Compared to controls, patients with craniosynostosis were more likely to be born preterm (OR 2.58, 95% CI = 1.09, 6.09), and to non-white mothers (OR 6.29, 95% CI = 2.20, 17.97). Twinning was also associated with a higher risk for craniosynostosis in one of the twins although the 95% CI was very wide (OR 15.09, 95% CI = 1.75, 130.22). There were no differences between groups with respect to patient race (cases = 65.85% white versus controls = 79.76%; P = 0.14), patient ethnicity (cases = 7.50% Hispanic or Latino versus controls = 3.61%; P = 0.39), infant sex (cases = 64.29% males versus controls = 50%; P = 0.18), primigravida versus multigravida (cases = 20.83% born to primigravida mothers versus controls = 43.37%; P = 0.08), cesarean versus vaginal delivery (cases = 55% delivered via cesarean section versus controls = 37.35%; P = 0.10), BMI greater than or equal to 30 (cases = 75% versus controls = 31.65%; P = 0.76), and/or maternal age greater than or equal to 35 years (cases = 14.29% versus controls = 14.29%; P = 1.00). Additionally, there were no differences between groups when comparing pregnancy complications including preeclampsia (cases = 21.43% versus controls = 14.29%; P = 0.45), hypertension (cases = 16.67% versus controls = 9.52%; P = 0.38), diabetes (cases = 11.90% versus controls =13.10%; P = 0.92), thyroid disease (cases = 4.76% versus controls = 10.71%; P = 0.33), polyhydramnios (cases = 7.14% versus controls = 7.14%; P = 1.00), oligohydramnios (cases = 4.76% versus controls = 1.19%; P = 0.55), tobacco use (cases = 7.14% versus controls = 10.71%; P = 0.75), and/or substance use (cases = 20.59% versus controls = 8.11% of cases; P = 0.13). No differences were identified between groups when comparing average maternal BMI (cases = 37.27 (9.98) versus controls = 34.40 (6.95); P = 0.15), maternal age (cases = 27.32 (5.64) versus controls = 28.60 (5.98); P = 0.36), birth weight in kilograms (cases = 2.75 (1.03) versus controls = 3.16. (0.64); P = 0.15), and/or birth head circumference in centimeters (cases = 31.62 (4.95) versus controls = 33.81 (1.98); P = 0.08). Conclusion: The study results indicate that craniosynostosis patients were more likely to be born from non-white mothers, have a preterm delivery, and be a member of a multiple gestation. These findings contribute to a better understanding of the risk factors associated with craniosynostosis, which may be used to assist with early diagnosis and effective intervention for affected patients. Due to the rarity of craniosynostosis, further studies with larger sample sizes are needed to more fully elucidate the risk factors for this condition and potential interventions for prevention.
Demirchian et al. (Sun,) studied this question.