American Journal of Epidemiology Advance Access published online on August 27, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn244
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Letter to the Editor |
RE: "RISK OF ORAL CLEFTS IN RELATION TO PREPREGNANCY WEIGHT CHANGE AND INTERPREGNANCY INTERVAL"
1 Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands
2 The Netherlands Perinatal Registry, P.O. Box 8588, 3503 RN Utrecht, the Netherlands
(e-mail: Luc.Smits{at}EPID.unimaas.nl)
In an earlier issue of this Journal, Villamor et al. (1) reported a strong, positive, linear association between interpregnancy interval and birth prevalence of cleft palate. We were surprised to see a linear increase in risk instead of a J-shaped association. Reported risks of adverse birth outcome typically peak at both ends of the interpregnancy interval spectrum, and lowest risks are found mostly for intervals between 12 and 23 months (2). Although the causes of these excess risks are still uncertain and probably different for short and long intervals (3), we have hypothesized that the increased risks associated with short interpregnancy intervals are (at least partly) attributable to maternal depletion of micronutrients, particularly folate (4). Pregnancy places a burden on maternal micronutrient reserves and, if a new conception occurs before these reserves are sufficiently restored, growth and development of the conceptus may be compromised. Pregnancies accomplished shortly after the preceding delivery, in addition, are more likely than others to be unintended (5), which decreases the probability that periconceptional folic acid (or multivitamin) supplements were used. As Villamor et al. note, the risk of orofacial clefts has been found to depend on periconceptional intake of folate and other micronutrients.
The authors mention that confirmation of their observation in other study populations is required, and we agree. We would, however, suggest an adjustment of the categorization of interpregnancy interval, because it is possible that the one used (<12, 12–23, 24–35, 36–47, 
48 months) was too broad to reveal any increased risks after short interpregnancy intervals. As a first move, Villamor et al. (1) might want to repeat their analyses with a more fine-tuned classification of short interpregnancy intervals (e.g., categories spanning no more than 3 months).
Because short interpregnancy intervals are—at least in principle—avoidable, any risks linked to them should not remain unnecessarily concealed.
ACKNOWLEDGMENTS
Conflict of interest: none declared.
References
- 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] - Conde-Agudelo A, Rosas-Bermúdez A, Kafury-Goeta AC. Birth spacing and risk of adverse perinatal outcomes: a meta-analysis. JAMA (2006) 295(15):1809–1823.
[Abstract/Free Full Text] - Royce R. Birth spacing—the long and short of it. JAMA (2006) 295(15):1837–1838.
[Free Full Text] - 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]
- Kaharuza FM, Basso O, Sabroe S. Choice or chance: determinants of short interpregnancy interval in Denmark. Acta Obstet Gynecol Scand (2001) 80(6):532–538.[CrossRef][Web of Science][Medline]
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  E. Villamor, P. Sparen, and S. Cnattingius The Authors Reply Am. J. Epidemiol., November 1, 2008; 168(9): 1093 - 1093. [Full Text] [PDF]
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