American Journal of Epidemiology Advance Access originally published online on August 27, 2008
American Journal of Epidemiology 2008 168(9):1093; doi:10.1093/aje/kwn245
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LETTERS TO THE EDITOR |
The Authors Reply
1 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115
2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, S-171 77 Stockholm, Sweden
(e-mail: evillamo{at}hsph.harvard.edu)
We thank Smits and Hukkelhoven (1) for their insight into the positive, linear association between interpregnancy interval and the risk of cleft palate in Sweden and their comments on our recent paper (2). We categorized the interpregnancy interval a priori, according to our previous study (3) on prepregnant weight change and adverse pregnancy outcomes. We would not have sufficient statistical power to examine the association between interpregnancy interval and cleft palate in finer categories, and we did not intend to test such a hypothesis; our finding was unexpected (2).
The notion that very short interpregnancy intervals could be associated with increased risk of cleft palate through depletion of maternal micronutrient reserves (4) is an intriguing one. If we were to categorize interpregnancy intervals into 3-month periods as suggested in the letter by Smits and Hukkelhoven (1), the birth prevalences of isolated cleft palate per 1,000 livebirths in our population would be 0.68 (<3 months), 0.17 (3–<6 months), 0.31 (6–<9 months), and 0.25 (9–<12 months) for women with intervals of less than 12 months. It might seem like the birth prevalence of these defects in women with the shortest interpregnancy intervals (<3 months) would indeed be higher than those of women with longer intervals. Nevertheless, we must note that the number of defects in each of those categories was 1, 1, 4, and 5, respectively, which severely hampers the possibility of making statistical inferences. In addition, a greater prevalence of cleft palate was not observed consistently throughout intervals shorter than 6 months in our data, contrary to the critical timing for depletion proposed in Smits and Essed's hypothesis (4).
We agree that the maternal depletion hypothesis is an interesting proposition, with potentially practical implications, that deserves testing in future studies.
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ACKNOWLEDGMENTS |
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Conflict of interest: none declared.
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References |
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 TOP References |
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- Smits LJM, Hukkelhoven CWPM. Re: "Risk of oral clefts in relation to prepregnancy weight change and interpregnancy interval" [letter]. Am J Epidemiol (2008) 168(9):1092–1093.
[Free Full Text] - Villamor E, Sparén P, Cnattingius S. Risk of oral clefts in relation to prepregnancy weight change and interpregnancy interval. Am J Epidemiol (2008) 167(11):1305–1311.
[Abstract/Free Full Text] - Villamor E, Cnattingius S. Interpregnancy weight change and risk of adverse pregnancy outcomes: a population-based study. Lancet (2006) 368(9542):1164–1170.[CrossRef][Medline]
- Smits LJ, Essed GG. Short interpregnancy intervals and unfavourable pregnancy outcome: role of folate depletion. Lancet (2001) 358(9298):2074–2077.[CrossRef][Web of Science][Medline]
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