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Updated: May 14, 2026
Midface Hypoplasia and Cranial Base Morphology in Syndromic Craniosynostosis: A Comparative Analysis Study Using a Predictive Regression Model
Published on: November 4, 2025
Risk factors associated with craniosynostosis: a case control study
Maryam Ardalan1, Ali Rafati, Farideh Nejat
1Department of Neurosurgery, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Insights
Family history of craniosynostosis and clomiphene citrate use are significant risk factors for this congenital abnormality. Further research is needed to explore environmental influences and reduce craniosynostosis occurrence.
Area of Science:
- Medical Genetics
- Pediatric Surgery
- Congenital Abnormalities
Background:
- Craniosynostosis is a common congenital condition with largely unknown causes.
- Identifying risk factors for craniosynostosis is crucial for understanding and potentially preventing it.
Purpose of the Study:
- To investigate potential risk factors associated with craniosynostosis.
- To identify independent predictors for craniosynostosis in a case-control study.
Main Methods:
- A case-control study involving 70 children with craniosynostosis and 70 matched controls.
- Data collected through parental interviews and checklists regarding medical history and medication use.
- Analysis focused on identifying correlations between various factors and craniosynostosis.
Main Results:
- The most commonly affected sutures were coronal (42.9%) and metopic (22.9%).
- Maternal diabetes mellitus (11.6%) and thyroid disease (8.6%) were noted in the case group.
- Mothers of affected children frequently used vitamins (94%) during pregnancy.
Conclusions:
- A positive family history (OR 19.01) and clomiphene citrate use (OR 12.71) were identified as strong independent risk factors.
- Further large-scale studies are necessary to confirm the role of environmental factors in craniosynostosis.
- Understanding these risk factors may aid in strategies to decrease craniosynostosis incidence.
Background:
Craniosynostosis is a relatively common congenital abnormality. The underlying etiology and most probable risk factors of nonsyndromic craniosynostosis are unknown. We conducted a study to identify the risk factors for craniosynostosis.
Materials And Methods:
In this case-control project, 70 children with craniosynostosis (syndromic or nonsyndromic) hospitalized at the Children's Hospital Medical Center from September 2010 to 2011 were studied for the potential risk factors. At the same time, 70 age- and sex-matched children hospitalized with other congenital anomalies were reviewed. Information from case and control groups was obtained via personal interviews with parents of patients and a prepared checklist was filled out for each child.
Results:
The mean (±SE) age at admission time in the case-control group was 13 ± 1.95 (1.5-96) months, and almost half of them were boys (n = 37 or 53%). The most frequent sutures involved in craniosynostosis were coronal (n = 30 or 42.9%) and then metopic sutures (n = 16 or 22.9%), multiple (n = 12 or 17.1%), sagittal (n = 11 or 15.7%) and lambdoid (n = 1 or 1.4%). In the case group, maternal diabetes mellitus and thyroid disease were found in 8 (11.6%) and 6 (8.6%) patients, respectively. The most frequent medication used by mothers (n = 66 or 94%) in the case group during pregnancy were vitamins (including iron supplements, omega 3, folic acid and multivitamins).
Conclusion:
A positive family history of craniosynostosis [odds ratio (OR) 19.01 and 95% confidence interval (CI) 2.24-160.7] and using clomiphene citrate for infertility (OR 12.71 and 95% CI 1.42-113.6) were the strongest independent risk factors for craniosynostosis. More comprehensive studies with a larger sample size are required to confirm the role of environmental factors in order to decrease the occurrence of craniosynostosis.
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