INCREASED RISK OF CRANIOSYNOSTOSIS WITH HIGHER ANTENATAL MATERNAL ALTITUDE

Background. During the 1980s, the Colorado Department of Health receiv ed reports from several high-altitude communities of clusters of the m alformation craniosynostosis. In a population-based, case-control stud y, we examined the association between overall and trimester-specific maternal antenatal altitude exposure and the occurrence of infant cran iosynostosis. Methods. We identified case children through a statewide registry and randomly sampled control children from birth records. By telephone interview, each mother provided data on the locations of al l antenatal residences and places of employment as well as other facto rs. Staff mapped all locations and abstracted the corresponding altitu des. Results. The odds ratio (OR) of any synostosis for a time-weighte d mean antenatal altitude of greater than or equal to 2000 metres (hig h altitude) versus <2000 metres (low altitude) was 1.4 (lower bound of the one-sided 95% test-based confidence interval (CI): 0.9). The OR w as elevated in smokers but not in non-smokers. As compared to non-smok ers, the OR of any synostosis for high-altitude smokers was 4.6 (lower bound of the 95% one-sided exact Cl : 1.7). Particularly elevated wer e the correspondinding OR of coronal (18.1, 4.4) and metopic synostosi s (16.3, 2.8), and OR for high-altitude exposure during the second tri mester (any synostosis: 6.4, 1.99; coronal: 28.6, 6.1; metopic: 26.7, 4.1). Conclusions. Antenatal maternal high-altitude exposure and smoki ng are associated with increased risk of infant craniosynostosis, perh aps through generation of intermittent hypoxaemia.