Paternal Homocysteine as a Biomarker for Early and Late Prenatal Growth Outcomes: a Prospective Cohort Study
Year: 2025
Type: preprint
Study design: Observational Study
Abstract: Objective : To investigate the association between paternal serum total homocysteine (tHcy) levels and prenatal growth trajectories. Design: Prospective cohort study conducted from 2010 to 2022. Setting: The Rotterdam Periconception Cohort (Predict Study). Population: 881 men and their female partners with tHcy levels measured in the first trimester of pregnancy. Methods: Lifestyle and socio-demographic data was obtained from self-reported questionnaires. Associations were measured with linear mixed models and piecewise regression models adjusted for confounders. Stratification occurred for cases of normal range homocysteine (<15µmol/L) and hyperhomocysteinemia (≥15µmol/L). Main Outcome Measures: First trimester crown-rump length and embryonic volume were measured with Virtual Reality and Artificial Intelligence. Second trimester fetal measurements were obtained from the standard fetal anomaly scan. Birth weight and pregnancy complications were extracted from medical records. Results: Males had an average tHcy concentration of 12.7µmol/L, and a rate of hyperhomocysteinemia of 17.7%. The association between paternal tHcy and crown-rump length was different if tHcy was <15 or ≥15µmol/L, showing a negative association if tHcy was ≥15µmol/L (difference in slope coefficients -0.016, 95% CI -0.029,-0.003, p=0.019). The difference persisted for fetal measurements such as abdominal circumference (difference in slope coefficients -0.393, 95% CI -0.729,-0.056, p=0.022) and estimated fetal weight (difference in slope coefficients -2.703, 95% CI -4.466,-0.941, p=0.003). No associations were found between paternal tHcy and birth weight, including small or large for gestational age neonates. Conclusions: Paternal tHcy may be a relevant biomarker for prenatal growth. Monitoring paternal tHcy levels and encouraging a healthy lifestyle and multivitamin use should be part of antenatal care and preconception counselling.
Institutions: Erasmus MC, University of Nottingham
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4412100711