Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study.
Suboptimal dietary intake during pregnancy may have long-term health implications in children. These effects may be mediated by fetal growth. We investigated the associations of early pregnancy and umbilical cord total homocysteine (tHcy), folate, and total and active vitamin B12 concentrations with fetal growth parameters repeatedly measured in pregnancy and at birth.



This study was performed in 5890 pregnant women, participating in a population-based prospective cohort study. Blood samples were obtained from women in early pregnancy and from the umbilical vein at delivery. Fetal size parameters were repeatedly measured by ultrasound. Information about birth anthropometrics was retrieved from medical records.



High early pregnancy maternal tHcy (≥8.31 μmol/L), as compared with low maternal homocysteine (≤5.80 μmol/L), and low early pregnancy maternal folate (≤9.10 nmol/L), as compared with high maternal folate (≥25.81 nmol/L) concentrations, were associated with reduced weight growth patterns throughout pregnancy, resulting in birthweight differences of -102.3 g (95% CI -139.6, -65.0) and -113.0 g (95% CI -159.6, -66.3), respectively. Low umbilical cord folate concentrations (≤15.20 nmol/L) as compared with high umbilical cord folate concentrations (≥28.41 nmol/L) were also associated with a lower birthweight and birth length (P < 0.001). Interestingly, compared with higher umbilical cord vitamin B12 , lower vitamin B12 concentrations were associated with a higher weight, length, and head circumference at birth (P < 0.01).



Early pregnancy maternal and umbilical cord markers of the homocysteine pathway are significantly associated with fetal growth patterns. These differences arise from mid-pregnancy onwards.
The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Division of Obstetrics & Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Nienke E
NE
Bergen
The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Division of Obstetrics & Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Sarah
S
Schalekamp-Timmermans
The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Vincent W V
VW
Jaddoe
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Albert
A
Hofman
Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Jan
J
Lindemans
Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Henk
H
Russcher
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Child and Adolescent Psychiatry, Erasmus MC, University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
Henning
H
Tiemeier
Division of Obstetrics & Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Régine P M
RP
Steegers-Theunissen
Division of Obstetrics & Prenatal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Eric A P
EA
Steegers
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D047109:Fetal Development; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D011446:Prospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood
D015415:Biomarkers; D011257:Pregnancy Proteins; D006710:Homocysteine; D005492:Folic Acid; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D014805:Vitamin B 12
early pregnancy; fetal growth; folate; homocysteine; prospective cohort study