Periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth trajectories: the Rotterdam Periconceptional Cohort (Predict Study)

Abstract

To study the associations between the periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth. Prospective, periconceptional hospital-based birth cohort. Tertiary medical care center. Between 2010 and 2014, 236 women with early singleton ongoing pregnancies that resulted in 139 strictly dated spontaneous pregnancies and 97 pregnancies conceived after assisted reproductive technology. None. Maternal serum vitamin B12 and plasma total homocysteine (tHcy) assessed at enrollment, and longitudinal first-trimester crown-rump length (CRL), embryonic volume (EV), and absolute growth rates obtained via three-dimensional ultrasound (3D-US) and virtual reality. In early pregnancy, we performed a median of five 3D-US scans (range: 1-7). Vitamin B12 concentrations were positively associated with CRL and EV measurements in the total population (CRL: β 5ˆ10-4 (1ˆ10-4 to 9ˆ10-4) √mm; EV: β 2ˆ10-4 (0ˆ10-4 to 4ˆ10-4) 3√cm3) and in the strictly dated spontaneous pregnancy subgroup. The tHcy concentration was negatively associated with embryonic growth in all study groups. High tHcy concentrations (+2 standard deviation [SD], 10.3μmol/L) were associated with a 1.7mm smaller CRL (-13.4%) at 7weeks and a 3.6-mm smaller CRL (-7.1%) at 11weeks compared with -2 SD tHcy (-3.0μmol/L). A high tHcy concentration was also associated with a 0.10cm3 smaller EV (-33.3%) at 7weeks and a 1.65cm3 smaller EV (-16.1%) at 11weeks. The embryonic growth rate was positively associated with vitamin B12 and negatively associated with tHcy. Minor variations in periconceptional maternal concentrations of one-carbon metabolism biomarkers are associated with human embryonic growth.