An investigation of folate-related genetic factors in the determination of birthweight

Caroline L Relton, Mark S Pearce, John Burn, Louise Parker

Research output: Contribution to journalArticle (Academic Journal)peer-review

22 Citations (Scopus)


Recent evidence suggests that maternal folate status in early gestation is a significant determinant of infant birthweight. Folate metabolism is known to be controlled by genetic factors, with a number of polymorphic variations in folate metabolising genes identified, several of which have well-documented functional effects. The current study investigated whether folate-related polymorphic variation, in association with low maternal folate status, influences birthweight. Red blood cell (RBC) folate analysis and genotyping of five polymorphisms in folate-related genes [Methylenetetrahydrofolate reductase (MTHFR) 677C>T; MTHFR 1298A>C; cystathionine-beta-synthase (CbetaS) 844ins68bp; serine hydroxymethyltransferase (SHMT) 1420C>T; reduced folate carrier-1 (RFC-1) 80G>A] were undertaken in mothers and infants from 998 pregnancies. These data were analysed in relation to infant birthweight, adjusted for gender and gestational age (z-score). Low maternal RBC folate status was associated with reduced infant birthweight. None of the genetic variants studied showed an independent association with infant birthweight. However, two genetic variants were shown to have a significant effect on birthweight when found in association with low maternal RBC folate status. When individuals with variant genotypes and mothers with folate in the lowest quintile were compared with wild-type individuals and mothers with folate in the highest quintile, the following differences in mean birthweight (z-score) were observed; maternal MTHFR 677C>T (-0.56 [95% CI -1.00, -0.12]P=0.01) and infant CbetaS 844ins68bp (-0.71 [95% CI -1.97, -0.07]P=0.03). The findings of this study suggest that folate-related genetic polymorphisms do not directly influence infant birthweight. However, when placed on a background of deficient maternal nutritional status, they may detrimentally affect fetal growth.

Original languageEnglish
Pages (from-to)360-7
Number of pages8
JournalPaediatric and Perinatal Epidemiology
Issue number5
Publication statusPublished - Sept 2005


  • Birth Weight
  • Cohort Studies
  • Cystathionine beta-Synthase
  • Erythrocytes
  • Female
  • Folic Acid
  • Genotype
  • Glycine Hydroxymethyltransferase
  • Humans
  • Infant, Newborn
  • Maternal-Fetal Exchange
  • Membrane Transport Proteins
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Polymorphism, Genetic
  • Pregnancy


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