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


METHODS
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.
van Eijsden
Manon
M
Department of Epidemiology, Documentation and Health Promotion, Municipal Health Service, Amsterdam, The Netherlands. mveijsden@ggd.amsterdam.nl
Smits
Luc J M
LJ
van der Wal
Marcel F
MF
Bonsel
Gouke J
GJ
D000328:Adult; D001721:Birth Intervals; D001724:Birth Weight / Q000187:drug effects* / Q000502:physiology; D015331:Cohort Studies; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011295:Prenatal Care; D039401:Prenatal Nutritional Physiological Phenomena; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
D005492:Folic Acid