The effect of maternal folate intake on small-for-gestational-age (SGA) births remains inconclusive. The present study aimed to investigate the associations of maternal folate intake from diet and supplements with the risk of SGA births using data from a cross-sectional study in Shaanxi Province of Northwest China. A total of 7307 women who were within 12 months (median 3; 10th–90th percentile 0–7) after delivery were included. Two-level models were adopted to examine the associations of folate (dietary folate, supplemental folic acid and total folate) intake with the risk of SGA births and birth weight Z score, controlling for a minimum set of confounders that were identified in a directed acyclic graph. Results showed that a higher supplemental folic acid intake during the first trimester was negatively associated with the risk of SGA births (≤60 d v. non-use: OR 0·80; 95 % CI 0·66, 0·96; >60 d v. non-use: OR 0·78; 95 % CI 0·65, 0·94; Ptrend = 0·010; per 10-d increase: OR 0·97; 95 % CI 0·95, 0·99). A higher total folate intake during pregnancy was associated with a reduced risk of SGA births (highest tertile v. lowest tertile: OR 0·77; 95 % CI 0·64, 0·94; Ptrend = 0·010; per one-unit increase in the log-transformed value: OR 0·81; 95 % CI 0·69, 0·95). A similar pattern was observed for the birth weight Z score. Our study suggested that folic acid supplementation during the first trimester and a higher total folate intake during pregnancy were associated with a reduced risk of SGA births.

Small size at birth continues to be a problem worldwide and many factors, including reduced folate intake and Pb exposure, are associated with it. However, single factors rarely explain the variability in birth weight, suggesting a need for more complex explanatory models. We investigated environment–gene interactions to understand whether folate intake and maternal Pb exposure were associated with smaller newborn size in 474 women with uncomplicated pregnancies delivering term infants in Mexico City. We examined if folate intake modified the negative effects of maternal Pb burden on birth size. We also asked if maternal and infant methylenetetrahydrofolate reductase (MTHFR) genotypes (C677T, A1298C and G1793A) modified the effects of folate intake or Pb exposure on birth size. Women were aged 24·6 (sd 5·1) years; 43·5 % were primiparous. Maternal blood Pb at delivery was 86 (sd 42) μg/l, with 26·7 % having levels ≥ 100 μg/l. Tibia Pb level was 9·9 (sd 9·8) μg/g. Of the women, 35·3 % had folate intakes < 400 μg/d. Birth weight was 3170 (sd 422) g. In covariate-adjusted regressions, higher folate intake was associated with higher birth weight (β 0·04; P < 0·05). Higher bone Pb was associated with lower birth weight (β − 4·9; P < 0·05). Folate intake did not modify the effects of Pb on birth size, nor did MTHFR modify the association between Pb or folate intake on birth size. Although modest, the relationship between maternal nutrition, Pb burden and birth size does underscore the importance of environmental exposures to child health because patterns of fetal growth may affect health outcomes well into adulthood.

Responses of several folate-metabolizing pathways to dietary folic acid were studied in 2-week-old chicks. Oxidation of a histidine load to carbon dioxide was impaired in folate-deficient chicks. There was a curvilinear relation between oxidation and dietary folate, and maximum oxidation occurred with 2 mg supplemental folic acid/kg. Hepatic activities of glutamic acid formiminotransferase (EC 2.1.2.5) and glycine N-methyltransferase (EC 2.1.1.20) were not affected significantly (P > 0.05) by dietary folic acid. The activity of dihydrofolate reductase (EC 1.5.1.3) in erythrocytes was elevated in folate-deficient chicks. These studies show that the activities of two folate-dependent pathways can be used as biochemical criteria of folate status in chicks.