Increased risk of craniosynostosis with higher antenatal maternal altitude.
BACKGROUND
During the 1980s, the Colorado Department of Health received reports from several high-altitude communities of clusters of the malformation craniosynostosis. In a population-based, case-control study, we examined the association between overall and trimester-specific maternal antenatal altitude exposure and the occurrence of infant craniosynostosis.


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 all antenatal residences and places of employment as well as other factors. Staff mapped all locations and abstracted the corresponding altitudes.


RESULTS
The odds ratio (OR) of any synostosis for a time-weighted mean antenatal altitude of > or = 2000 metres (high 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 was elevated in smokers but not in non-smokers. As compared to non-smokers, the OR of any synostosis for high-altitude smokers was 4.6 (lower bound of the 95% one-sided exact CI: 1.7). Particularly elevated were the corresponding OR of coronal (18.1, 4.4) and metopic synostosis (16.3, 2.8), and OR for high-altitude exposure during the second trimester (any synostosis: 6.4, 1.99; coronal: 28.6, 6.1; metopic: 26.7, 4.1).


CONCLUSIONS
Antenatal maternal high-altitude exposure and smoking are associated with increased risk of infant craniosynostosis, perhaps through generation of intermittent hypoxaemia.
Alderman
B W
BW
Department of Epidemiology, University of Washington, Seattle, USA.
Zamudio
S
S
Barón
A E
AE
Joshua
S C
SC
Fernbach
S K
SK
Greene
C
C
Mangione
E J
EJ
D000531:Altitude; D016022:Case-Control Studies; D003120:Colorado / Q000453:epidemiology; D003398:Craniosynostoses / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D016017:Odds Ratio; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects