title: Low folate status enhances pregnancy changes in plasma betaine and dimethylglycine concentrations and the association between betaine and homocysteine.
abstract: BACKGROUND
  Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy.
  
  
  OBJECTIVE
  The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy.
  
  
  METHODS
  Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at <12, 15, 24-27, and 34 gestational weeks (GW); at labor (nonfasting); and in the cord in participants (n = 522) from the Reus-Tarragona Birth Cohort (NUTrició i Creixement Intrauterí Retardat phase). Timing, dose, and duration of folic acid supplement use were recorded. Folate status was classified as below (low) or above (high) median plasma folate at baseline (27.6 nmol/L) and at 24-27 GW (11.4 nmol/L). Associations between folate or betaine with tHcy were investigated by using multiple linear regression analysis.
  
  
  RESULTS
  Plasma betaine decreased by 34.8% (1.0%) throughout pregnancy, and dimethylglycine increased by 39.7% (2.7%) between 24-27 GW and labor (all P < 0.001). Compared with high folate status, low status was associated with a higher dimethylglycine/betaine ratio from 15 GW and with lower plasma betaine and higher dimethylglycine from 24 to 27 GW, for the rest of pregnancy. Regression analysis showed that by 24-27 GW, both plasma folate and betaine were inversely associated with tHcy when folate status was low and that the association between betaine and tHcy depended on folate status at 24-27 and 34 GW (interaction terms: P < 0.001 and P < 0.01). Betaine was inversely associated with tHcy at labor regardless of folate status.
  
  
  CONCLUSIONS
  Low folate status enhances the reduction in betaine and the increase in dimethylglycine during pregnancy and strengthens the association between betaine and tHcy. This trial was registered at clinicaltrials.gov as NCT01778205.
authors.affiliation: Area of Preventive Medicine and Public Health, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Fernàndez-Roig
authors.forename: Pere
authors.initials: P
authors.lastname: Cavallé-Busquets
authors.forename: Joan D
authors.initials: JD
authors.lastname: Fernandez-Ballart
authors.forename: Monica
authors.initials: M
authors.lastname: Ballesteros
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Berrocal-Zaragoza
authors.forename: Judith
authors.initials: J
authors.lastname: Salat-Batlle
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Murphy
mesh_terms: D000328:Adult; D001622:Betaine / Q000097:blood*; D002794:Choline / Q000097:blood; D019587:Dietary Supplements; D005215:Fasting; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D009752:Nutritional Status; D011247:Pregnancy; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000097:blood; D013030:Spain; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D001622:Betaine; C025138:dimethylglycine; D005492:Folic Acid; D002794:Choline; D014805:Vitamin B 12; D012521:Sarcosine