title: Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study.
abstract: OBJECTIVE
  To investigate associations between early pregnancy homocysteine, folate and vitamin B12 concentrations and placental weight, birthweight and adverse pregnancy outcomes.
  
  
  METHODS
  Population-based birth cohort study.
  
  
  METHODS
  Rotterdam, the Netherlands.
  
  
  METHODS
  Cohort of 5805 pregnant women.
  
  
  METHODS
  To analyse homocysteine, folate and vitamin B12 concentrations, blood was drawn in early pregnancy. These concentrations were divided into quintiles. Information on birth outcomes was retrieved from medical records. Multivariate regression analyses were used.
  
  
  METHODS
  Placental weight, birthweight, small for gestational age at birth (SGA) (<5th centile), prematurity and pre-eclampsia.
  
  
  RESULTS
  High homocysteine concentrations (highest quintile) were associated with lower placental weight (difference 30 g; P < 0.001) and birthweight (difference 110 g; P < 0.001), and increased risk of SGA [odds ratio (OR) 1.7; P = 0.006] compared with lowest quintile (reference). Low folate concentrations (lowest quintile) were associated with lower placental weight (difference 26 g; P = 0.001) and birthweight (difference 125 g; P < 0.001), and increased risks of SGA (OR 1.9; P = 0.002), prematurity (OR 2.2; P = 0.002) and pre-eclampsia (OR 2.1; P = 0.04) compared with highest quintile (reference). The risk of developing SGA and pre-eclampsia was substantially higher in women who had higher homocysteine and lower folate concentrations. No associations were found with vitamin B12.
  
  
  CONCLUSIONS
  Higher homocysteine and lower folate concentrations in early pregnancy are associated with lower placental weight and birthweight, and higher risk of adverse pregnancy outcomes. These findings suggest that high homocysteine and low folate concentrations in early pregnancy may adversely influence placentation and subsequently affect the success of pregnancy and birth outcomes.
authors.affiliation: The Generation R Study Group, Department of Obstetrics and Gynaecology/Division of Obstetrics and Prenatal Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands. n.bergen@erasmusmc.nl
authors.forename: N E
authors.initials: NE
authors.lastname: Bergen
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: S
authors.initials: S
authors.lastname: Timmermans
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: J
authors.initials: J
authors.lastname: Lindemans
authors.forename: H
authors.initials: H
authors.lastname: Russcher
authors.forename: H
authors.initials: H
authors.lastname: Raat
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
mesh_terms: D000328:Adult; D001724:Birth Weight; D015331:Cohort Studies; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D009426:Netherlands; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology*; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy; D011256:Pregnancy Outcome; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood*; D055815:Young Adult
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12