The Effect of Interactions between Folic Acid Supplementation and One Carbon Metabolism Gene Variants on Small-for-Gestational-Age Births in the Screening for Pregnancy Endpoints (SCOPE) Cohort Study.

Small-for-gestational-age (SGA) is associated with significant perinatal morbidity and mortality. Our aim was to investigate gene-nutrient interactions between maternal one-carbon single nucleotide polymorphisms (SNPs) and folic acid supplement (FAS) use, and their association with SGA. Nulliparous New Zealand women with singleton pregnancy were recruited as part of the Screening for Pregnancy Endpoints prospective cohort study. Data on FAS use was collected via face-to-face interview at 15 weeks' gestation; participants were followed prospectively and birth outcome data collected within 72 h of delivery. Participants were genotyped for MTHFR 677, MTHFR 1298, MTHFD1 1958, MTR 2756, MTRR 66 and TCN2 776 SNPs. Genotype data for at least one SNP was available for 1873 (93%) of eligible participants. Analysis showed a significant SNP-FAS interaction for MTHFR 1298 (p = 0.020), MTHFR 677 (p = 0.019) and TCN2 776 (p = 0.017) in relation to SGA: MTHFR 1298 CC variant non-FAS users had an increased likelihood [Odds Ratio (OR) = 2.91 (95% Confidence Interval (CI) = 1.52, 5.60] compared with wild-type (MTHFR 1298 AA) FAS users. MTHFR 677 variant allele carrier (MTHFR 677 CT + MTHFR 677 TT) non-FAS users had an increased likelihood [OR = 1.87 (95% CI = 1.21, 2.88)] compared to wild-type (MTHFR 677 CC) FAS users. TCN2 776 variant (TCN2 776 GG) non-FAS users had an increased likelihood [OR = 2.16 (95% CI = 1.26, 3.71)] compared with wild type homozygote + heterozygote (TCN2 776 CC + TCN2 776 CG) FAS users. No significant interactions were observed for MTHFD1 1958, MTR 2756 or MTRR 66 (p > 0.05). We observed an overall pattern of FAS attenuating differences in the likelihood of SGA seen between genotype groups in FAS non-users. Future research should focus on how intake of other one-carbon nutrients might mediate these gene-nutrient interactions.

Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study.

BACKGROUND: Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. AIM: The aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. STUDY DESIGN: Women were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. SUBJECTS: Nulliparous women with singleton pregnancies. OUTCOME MEASURES: SGA (<10th customised birthweight centile). RESULTS: 5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67-01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (ß 2.56 (95% CI: 0.87-4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. CONCLUSIONS: In this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.

Plasma folate and its association with folic acid supplementation, socio-demographic and lifestyle factors among New Zealand pregnant women.

Folic acid (FA) supplementation is recommended in the periconceptional period, for the prevention of neural tube defects. Limited data are available on the folate status of New Zealand (NZ) pregnant women and its association with FA supplementation intake. Objectives were to examine the relationship between plasma folate (PF) and reported FA supplement use at 15 weeks' gestation and to explore socio-demographic and lifestyle factors associated with PF. We used data and blood samples from NZ participants of the Screening for Pregnancy Endpoints cohort study. Healthy nulliparous women with singleton pregnancy (n 1921) were interviewed and blood samples collected. PF was analysed via microbiological assay. Of the participants, 73 % reported taking an FA supplement at 15 weeks' gestation - of these, 79 % were taking FA as part of/alongside a multivitamin supplement. Of FA supplement users, 56 % reported consuming a daily dose of ≥800 µg; 39 % reported taking less than 400 µg/d. Mean PF was significantly higher in women reporting FA supplementation (54·6 (se 1·5) nmol/l) v. no FA supplementation (35·1 (se 1·6) nmol/l) (P<0·0001). Reported daily FA supplement dose and PF were significantly positively correlated (r 0·41; P<0·05). Younger maternal age, Pacific and Maori ethnicity and obesity were negatively associated with PF levels; vegetarianism was positively associated with PF. Reported FA supplement dose was significantly associated with PF after adjustment for socio-demographic, lifestyle confounders and multivitamin intake. The relationship observed between FA supplementation and PF demonstrates that self-reported intake is a reliable proxy for FA supplement use in this study population.

Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis.

BACKGROUND: Preeclampsia is a significant contributor to maternal and neonatal morbidity and mortality. Folic acid supplementation is recommended periconceptionally for the prevention of neural tube defects. Epidemiological evidence suggests that maternal folic acid supplementation may play a role in preventing other adverse birth outcomes. This systematic review aimed to investigate the effect of maternal folic acid supplementation during pregnancy on risk of preeclampsia and gestational hypertension. METHODS: Multiple scientific databases and grey literature were searched for relevant studies. Studies were reviewed according to pre-specified inclusion and exclusion criteria. Study characteristics were summarised and study quality was assessed. A meta-analysis of observational studies was conducted to examine the effect of maternal folic acid supplementation on preeclampsia risk. RESULTS: Meta-analysis of eight observational studies showed significantly lower odds of preeclampsia with folic acid supplementation in comparison to no folic acid supplementation: OR = 0.78 (95% CI 0.63, 0.98), with moderately high heterogeneity between studies. Subgroup analysis showed no significant subgroup difference between folic acid supplementation taken by itself, in comparison to folic acid taken in or alongside a multivitamin. CONCLUSION: Low level evidence is available for a modest association between maternal folic acid supplementation and reduction in preeclampsia risk. Future studies should differentiate between early and late onset and mild vs severe preeclampsia, and should control for relevant confounders including the presence of multivitamin supplements. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42015029310).