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

Objective: To study the associations between the periconceptional maternal biomarkers of one-carbon metabolism and embryonic growth. Design: Prospective, periconceptional hospital-based birth cohort. Setting: Tertiary medical care center. Patient(s): 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. Intervention(s): None. Main Outcome Measure(s): 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. Result(s): 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], 10.3 μmol/L) were associated with a 1.7 mm smaller CRL (-13.4%) at 7 weeks and a 3.6-mm smaller CRL (-7.1%) at 11 weeks compared with -2 SD tHcy (-3.0 μmol/L). A high tHcy concentration was also associated with a 0.10 cm3 smaller EV (-33.3%) at 7 weeks and a 1.65 cm3 smaller EV (-16.1%) at 11 weeks. The embryonic growth rate was positively associated with vitamin B12 and negatively associated with tHcy. Conclusion(s): Minor variations in periconceptional maternal concentrations of one-carbon metabolism biomarkers are associated with human embryonic growth.

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