Introduction: Maternal elevated plasma total homocysteine (tHcy) is involved in the origin of several placenta-related pregnancy complications. The first trimester is the most sensitive period for placentation influenced by maternal and paternal health. The aim is to study associations between periconceptional parental tHcy levels and utero-placental growth trajectories in the first trimester of pregnancy. Methods: Pregnant women and their partners were enrolled before 10 weeks of gestation in the Virtual Placenta study as subcohort of the Rotterdam periconception cohort (Predict study). A total of 190 women with a singleton pregnancy, of which 109 conceived naturally and 81 after IVF/ICSI treatment, were included. We measured serial utero-placental vascular volumes (uPVV) and placental volumes (PV) at 7, 9 and 11 weeks of gestation. First-trimester trajectories of PV were also measured in 662 pregnancies from the total Predict study. Results: Comparing all participants of the virtual placenta study, no association between maternal tHcy and uPVV was observed. However, in IVF/ICSI pregnancies sub-analyses showed significantly negative associations between maternal tHcy in the 3rd and 4th quartile and uPVV trajectories (beta: −0.38 (95%CI -0.74 to −0.02) and beta: −0.42 (95% CI -0.78 to −0.05), respectively) with the 1st quartile as reference. Analysis in the total Predict cohort showed similar negative associations for the total study population. Discussion: Periconceptional high maternal tHcy levels are associated with smaller placental growth trajectories depicted as PV and uPVV in the first trimester of pregnancy. The stronger negative associations with uPVV in IVF/ICSI pregnancies underline the need for further investigation.
The Rotterdam periconception cohort (Predict Study) is conducted by the department of Obstetrics and Gynecology at the Erasmus MC, University Medical Center, Rotterdam. We gratefully acknowledge the Rotterdam Periconception Cohort team for data acquisition and the participating couples, gynecologists, and midwifery practices in Rotterdam for their contributions. The authors thank Anton Koning for technical support.
© 2021 The Author(s)