Fetal Constraint as a Potential Risk Factor for Craniosynostosis

Children's Hospital Los Angeles, Keck School of Medicine at University of Southern California, Los Angeles, California 90027, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 02/2010; 152A(2):394-400. DOI: 10.1002/ajmg.a.33246
Source: PubMed


Non-syndromic craniosynostosis is multifactorial, and fetal head constraint has been hypothesized as one factor thought to play a role. Data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, were used to evaluate associations between four selected factors related to fetal constraint and craniosynostosis: plurality (twins or higher), macrosomia (birth weight >4,000 g), post-term gestational age (> or =42 weeks), and nulliparity (no previous live births). Case infants (n = 675) had craniosynostosis documented either by radiographic evidence or by surgical intervention. Infants with a recognized or strongly suspected single-gene conditions or chromosomal abnormalities were excluded. Control infants (n = 5,958) had no major birth defects and were randomly selected from the same population as case infants. Logistic regression was used to estimate odds ratios for the association between these four factors and craniosynostosis, while adjusting for several covariates. We found that plurality and nulliparity were associated with a twofold increased risk for metopic craniosynostosis, and macrosomia had almost twice the risk of developing coronal craniosynostosis. Contrary to our hypothesis, prematurity and low birth weight were also associated with craniosynostosis. In conclusion, these four constraint-related factors were not found to be associated with craniosynostosis when all suture types were combined, though some types of craniosynostosis were associated with individual constraint-related factors.

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    • "The associations of craniosynostosis with many of the studied risk factors have been studied previously [Reefhuis et al., 2003; Carmichael et al., 2008; Boulet et al., 2010; Sanchez-Lara et al., 2010; Richardson et al., 2011].The novelty of the current study is that they have been examined simultaneously in the context of a unifying hypothesis regarding thyroid disease, and they have all been adjusted for confounding by each other. Previous studies have typically focused on one or a few risk factors at a time, adjusted for fewer covariates, included fewer cases, and did not exclude women diagnosed with overt thyroid disease. "
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    ABSTRACT: Thyroid disease is a common problem among women of reproductive age but often goes undiagnosed. Maternal thyroid disease has been associated with increased risk of craniosynostosis. We hypothesized that known risk factors for thyroid disease would be associated with risk of craniosynostosis among women not diagnosed with thyroid disease. Analyses included mothers of 1,067 cases and 8,494 population-based controls who were interviewed for the National Birth Defects Prevention Study. We used multivariable logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). After excluding women with diagnosed thyroid disease, younger maternal age (AOR 0.7, 95% CI 0.6-0.9, for <25 years versus 25-29), black or other race-ethnicity (AOR 0.3, 95% CI 0.2-0.4 and AOR 0.6, 95% CI 0.4-0.8, respectively, relative to non-Hispanic whites), fertility medications or procedures (AOR 1.5, 95% CI 1.2-2.0), and alcohol consumption (AOR 0.8, 95% CI 0.7-0.9) were associated with risk of craniosynostosis, based on confidence intervals that excluded 1.0. These associations with craniosynostosis are consistent with the direction of their association with thyroid dysfunction (i.e., younger age, black race-ethnicity and alcohol consumption are associated with reduced risk and fertility problems are associated with increased risk of thyroid disease). This study thus provides support for the hypothesis that risk factors associated with thyroid dysfunction are also associated with risk of craniosynostosis. Improved understanding of the potential association between maternal thyroid function and craniosynostosis among offspring is important given that craniosynostosis carries significant morbidity and that thyroid disease is under-diagnosed and potentially modifiable. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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    ABSTRACT: Craniosynostosis results from the premature fusion of one or more cranial sutures. The authors discuss historical aspects and treatment of craniosynostosis. Classic syndromes have been described based on the sutures involved and the resultant deformities. Treatments have evolved over the years and are tailored to the individual patient, with the goal of surgery being to restore a normal skull contour and allow continued growth of the brain to reshape the skull. All of this requires a multidisciplinary effort to achieve the desired results.
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    ABSTRACT: Craniosynostosis, defined as the premature fusion of the cranial sutures, presents many challenges in classification and treatment. At least 20% of cases are caused by specific single gene mutations or chromosome abnormalities. This article maps out approaches to clinical assessment of a child presenting with an unusual head shape, and illustrates how genetic analysis can contribute to diagnosis and management.
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