Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study

Abstract

Countries worldwide, including the Netherlands, recommend that women planning pregnancy use a folic acid supplement during the periconception period. Some countries even fortify staple foods with folic acid. These recommendations mainly focus on the prevention of neural tube defects, despite increasing evidence that folic acid may also influence birth weight. We examined whether periconception folic acid supplementation affects fetal growth and the risks of low birth weight, small for gestational age (SGA) and preterm birth, in the Generation R Study in Rotterdam, the Netherlands. Main outcome measures were fetal growth measured in mid-and late pregnancy by ultrasound, birth weight, SGA and preterm birth in relation to periconception folic supplementation (0·4 -0·5 mg). Data on 6353 pregnancies were available. Periconception folic acid supplementation was positively associated with fetal growth. Preconception folic acid supplementation was associated with 68 g higher birth weight (95 % CI 37·2, 99·0) and 13 g higher placental weight (95 % CI 1·1, 25·5), compared to no folic acid supplementation. In these analyses parity significantly modified the effect estimates. Start of folic acid supplementation after pregnancy confirmation was associated with a reduced risk of low birth weight (OR 0·61, 95 % CI 0·40, 0·94). Similarly, reduced risks for low birth weight and SGA were observed for women who started supplementation preconceptionally, compared to those who did not use folic acid (OR 0·43, 95 % CI 0·28, 0·69 and OR 0·40, 95 % CI 0·22, 0·72). In conclusion, periconception folic acid supplementation is associated with increased fetal growth resulting in higher placental and birth weight, and decreased risks of low birth weight and SGA.

Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort

“…Hypermethylation of the H19 DMR has been linked to relaxation of imprint controls, increased transcription and translation of the potent IGF2 growth mitogen, 58 and higher birth weight. 59 Our findings are consistent with those of previous studies in which FA intake before or/and during pregnancy or folate levels were associated with DNA methylation differences of a similar magnitude at this imprinted domain [46][47][48][49]60 and early childhood obesity. [61][62][63] Similar to the IGF2/H19 imprinted domain where IGF2 and H19 are reciprocally imprinted, the DLK1 and MEG3 genes, located on chromosome 14q32.2, are also reciprocally imprinted.…”

The Generation R Study: design and cohort update 2012

“…Various sociodemographic and lifestyle related determinant seems to affect these fetal growth and birth outcomes [114][115][116][117][118][119]. Also, specific fetal growth patterns seem to be associated with outcomes in childhood [120][121][122][123]. We have demonstrated in a subgroup study among mothers with a known and reliable last menstrual period, that various life style related factors affect first trimester growth [124].…”

Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: meta-analysis and meta-regression

“…Micronutrient supplementation before pregnancy also warrants further research. 42,43 Among Bhutanese refugees dependent on food aid, the incidence of low birth weight declined from 16% to 8% after 2 to 3 years of implementation of micronutrientfortified blended foods. 44 In conclusion, we found that maternal micronutrient supplementation can reduce the risk of low birth weight but has no overall effect on perinatal mortality in developing countries.…”