Association between short interpregnancy intervals and term birth weight: the role of folate depletion

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

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

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).

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.

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.