ABSTRACT
OBJECTIVES: This study was undertaken to test novel genetic polymorphisms involved in 1-carbon metabolism for a potential association with increased risk of developing pregnancy complications associated with uteroplacental insufficiency. STUDY DESIGN: This was a prospective cohort study consisting of 50 women at low risk and 93 women at high risk for having a pregnancy complication develop. Maternal and fetal DNA samples were genotyped for methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A. A chi squared or chi(2) analysis was used to compare genotypes and pregnancy outcome, 1-way analysis of variance and linear regression were used to compare genotype with continuous variables. RESULTS: The fetal MTR 2756 G allele was associated with uteroplacental insufficiency (P = .022, likelihood ratio = 10.4) and maternal homocysteine (P = .017). The maternal MTR A2756G polymorphism was associated with uteroplacental insufficiency (P = .049, likelihood ratio = 6.0), but only in mothers not supplementing with high-dose B-vitamins. The maternal MTHFD1 AA genotype was associated with intrauterine growth restriction (P = .047, likelihood ratio = 5.8). CONCLUSION: This study suggests the maternal and fetal MTR 2756 G allele is an important risk factor in the development of uteroplacental insufficiency. In addition, the maternal MTHFD1 1958 AA genotype may be associated with intrauterine growth restriction.
Subject(s)
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/genetics , Ferredoxin-NADP Reductase/genetics , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Placental Insufficiency/metabolism , Polymorphism, Single Nucleotide , Adult , Alleles , Birth Weight , Carbon/metabolism , Female , Fetal Growth Retardation/genetics , Humans , Maternal Age , Pre-Eclampsia/physiopathology , Pregnancy , Prospective Studies , Risk Assessment , Risk FactorsABSTRACT
OBJECTIVE: To determine if maternal circulating red blood cell (RBC) folate concentration in early pregnancy is associated with late gestation pregnancy complications including small for gestational age (SGA) infants, preeclampsia and preterm birth (PTB) in a socioeconomically disadvantaged population. METHOD: This was a retrospective case control study, conducted at Lyell McEwin Health Service, South Australia, including 400 primiparous women. RBC folate and demographic data were collected at 10-12 weeks gestation. Pregnancy outcome data were obtained from patient case notes. RESULTS: Patients who were folate deficient were more likely to develop pregnancy complications, specifically SGA (OR 6.9, 95% CI 2-24.3) and PTB (OR 5.4 95% CI 1.4-21.2). Those who were folate insufficient were also at increased risk of SGA (OR 3.0, 95% CI 1.3-7.7). No association between folate and preeclampsia was found. Women who were supplementing with folic acid delivered infants who were 179 g heavier (5.5% increased birth weight, P = 0.003) and 4.5 days later, compared to those who did not supplement. Furthermore, low RBC folate was associated with cigarette smoking (P < 0.001). CONCLUSIONS: Maternal RBC folate concentration in early pregnancy is associated with SGA and PTB, but not with preeclampsia.