Retracted: Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study

Abstract

BackgroundHealth authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD).MethodsThe Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628).ResultsThe median total folate intake was 266 μg/d (interquartile range IQR 154–543) in the overall population and 540 μg/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.ConclusionsOur findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

Folic acid supplementation, dietary folate intake and risk of preterm birth in China

“…Other studies did not explore this association by duration of maternal supplementation. Consistent with several earlier studies [22,23,27], but not all [17,20,29,30], we found that higher dietary folate intake during pregnancy was associated with reduced risk of PB and certain subtypes. We did not observe a synergistic effect between dietary folate and folic acid supplements.…”

“…Earlier epidemiological studies investigating the associations between PB and folic acid supplements/dietary folate intake have provided conflicting results [17][18][19][20][21][22][23][24][25][26][27][28][29][30]42]; among them, Dunlop et al [43] investigated plasma level of folate. While ten studies have reported a protective effect of folic acid supplements/dietary folate intake on PB [18][19][20][21][22][23][24][25][26][27], one study reported that risk of PB associated with folic acid supplement use varied by time periods of use (preconception, first trimester, and second trimester) [17] and four studies found no association [28][29][30]42]. Variations in dosage of folic acid use, selected pregnancy period of use, definitions of PB by gestational age, and lack of consideration of PB clinical subtypes among different populations might partially contribute to the inconsistent results.…”

“…Randomized controlled trials linking maternal folic acid supplementation to PB have reported inconsistent findings [10][11][12][13][14][15][16]. Epidemiologic studies examining folic acid supplementation/dietary folate and PB have also reported mixed results, including positive [17], negative [18][19][20][21][22][23][24][25][26][27], and null findings [28][29][30].…”

Assessment of Factors Associated with Adherence to Iron-Folic Acid Supplementation Among Urban and Rural Pregnant Women in North Western Zone of Tigray, Ethiopia: Comparative Study

“…Similarly, fetal and neonatal risks include prematurity, low birth weight, fetal distress which contribute to perinatal morbidity and mortality as well as infants born to Rural Pregnant Women in North Western Zone of Tigray, Ethiopia: Comparative Study anemic mothers will more likely to become anemic themselves [4,5]. Folic acid deficiency at conception and in early pregnancy is associated with increased risk of neural tube defects and other adverse pregnancy outcomes such as preeclampsia, malformations such as orofacial clefts, spontaneous abortion, fetal death, fetal growth restriction and preterm delivery [6,7]. Anemia during pregnancy is defined by the Centers of Disease Control and prevention as a hemoglobin <11g/dl [8].…”

Folic acid supplementation and dietary folate intake, and risk of preeclampsia

“…Several epidemiological studies have investigated the association between folic acid supplementation and the risk of preeclampsia; however, results from these studies have been inconsistent. Three studies found that folic acid-containing multivitamins were associated with reduced risk of preeclampsia, 14–16 three studies reported no association with folic acid supplement alone 17,18 and one study observed that dietary folate intake reduced the risk of preeclampsia. 19 …”