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American Journal of Epidemiology Advance Access published online on March 28, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn065
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Risk of Oral Clefts in Relation to Prepregnancy Weight Change and Interpregnancy Interval

Eduardo Villamor1, Pär Sparén2 and Sven Cnattingius2

1 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA
2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Correspondence to Dr. Eduardo Villamor, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115 (e-mail: evillamo{at}hsph.harvard.edu).

Received for publication December 19, 2007. Accepted for publication February 26, 2008.

Epidemiologic evidence regarding the influence of maternal obesity on the risk of oral clefts is inconsistent. It is unknown whether increases in maternal weight before pregnancy are related to the risk of these malformations. The authors conducted a population-based cohort study in Sweden among 220,328 women who had their first two pregnancies between 1992 and 2004. The risk of oral clefts during the second pregnancy was estimated in relation to maternal change in body mass index (BMI; weight (kg)/height (m)2) from the beginning of the first pregnancy to the beginning of the second pregnancy. Among women whose second-pregnancy BMI was ≥3 units higher than their first-pregnancy BMI, the adjusted risk of isolated cleft palate was 2.3 times higher (95% confidence interval: 1.4, 4.0) as compared with women whose BMI did not change substantially. BMI change was not related to the risk of cleft lip. Unexpectedly, the birth prevalence of isolated cleft palate per 1,000 livebirths increased linearly with the length of the interpregnancy interval, from 0.3 in women with intervals of <12 months to 0.9 in women with intervals of ≥48 months (adjusted p for trend = 0.002). High prepregnancy maternal weight gain and long interpregnancy intervals appear to be associated with increased risk of cleft palate.

birth intervals; body mass index; cleft lip; cleft palate; obesity; pregnancy

Abbreviations: BMI, body mass index; CI, confidence interval; CL + CLP, cleft lip with or without cleft palate; CP, cleft palate; ICD, International Classification of Diseases; SD, standard deviation


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