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Association between short interpregnancy intervals and term birth weight: the role of folate depletion^1,2,3

¹ From the Department of Epidemiology, Documentation and Health Promotion, Municipal Health Service, Amsterdam, Netherlands (MvE and MFvdW); the Department of Social Medicine, Public Health Epidemiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands (MvE and GJB); the Department of Epidemiology, Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands (LJMS); and the Institute of Health Policy and Management, Erasmus Medical Center, Rotterdam, Netherlands (GJB)

Background: Maternal folate depletion has been proposed as a primary explanation for the excess risk of fetal growth restriction associated with short interpregnancy intervals.

Objective: We aimed to evaluate the folate depletion hypothesis in a community-based cohort of pregnant women.

Design: Using a subsample of the cohort (multiparous participants who delivered a liveborn singleton infant, n = 3153), we investigated the relation between an increase in the interpregnancy interval (from 1 to 24 mo, natural log transformation) and birth weight and the risk of small-for-gestational-age (SGA) in 3 strata of maternal periconceptional folic acid use: nonuse, late use (begun after conception), and early use (begun before conception).

Results: Each increase in the interpregnancy interval on the natural log (ln) scale was associated with a mean (±SE) increase of 63.1 ± 20.3 g in birth weight (P = 0.002). This relation was mitigated by folic acid use: the change in birth weight was increases of 165.2 ± 39.6 g for nonuse (P < 0.001) and 33.5 ± 35.6 g for late use (P = 0.347) and a decrease of 5.9 ± 33.6 g for early use (P = 0.861). The birth weight differences were directly translated into SGA risk. Odds ratios per 1-mo increase in ln(interpregnancy interval) were significant for the total group (0.61; 95% CI: 0.46, 0.82) and for nonuse (0.38; 0.24, 0.60) and nonsignificant for late (0.83; 0.48, 1.44) and early (1.28; 0.58, 2.84) use.

Conclusions: Folate depletion apparently contributes to the excess risk of fetal growth restriction that is associated with short interpregnancy intervals. As a preventive option, postnatal supplementation may be beneficial, but confirmation is needed.

This article has been cited by other articles:

				I. Cetin, C. Berti, and S. Calabrese Role of micronutrients in the periconceptional period Hum. Reprod. Update, June 30, 2009; (2009) dmp025v1. [Abstract] [Full Text] [PDF]