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Maternal vitamin B₁₂ status in early pregnancy and its association with birth outcomes and newborn vitamin B₁₂ status Tan, Amy


Vitamin B₁₂ (B₁₂), a coenzyme required for DNA synthesis, methylation, and myelination, is important for fetal growth and development. Lower maternal B₁₂ status has been associated with preterm birth (<37 gestational weeks) and low birth weight (<2,500 grams), which are linked to morbidity and mortality across the lifespan. In Canada, 17-25% of women in early pregnancy were classified as B₁₂ deficient (serum total B₁₂ concentration <148 pmol/L) and maternal total B₁₂ concentration decreases throughout pregnancy; however, there is limited research on whether maternal B₁₂ status is associated with birth outcomes in Canadian pregnant women. This study aimed to determine the association between maternal B₁₂ status and birth outcomes and newborn functional B₁₂ status, and to identify predictors of newborn functional B₁₂ status. A secondary analysis of 709 mother-newborn pairs in British Columbia (BC), Canada, was conducted. Bio-banked first- (n=656) and second-trimester (n=709) maternal serum samples of apparently healthy South Asian (50%) and European (50%) women from the BC Prenatal Genetic Screening Program were quantified for B₁₂ biomarkers (total B₁₂, holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy)). Functional newborn B₁₂ status was indicated by MMA quantified in dried blood spots (DBSs). Obstetric history and birth outcome data were obtained from the BC Perinatal Data Registry. All associations were determined using multiple linear regression. Maternal B₁₂ biomarker concentrations were not linearly associated with birth weight z-score, head circumference z-score and gestational age at birth. However, a 10-pmol/L increase in first- and second-trimester maternal total B₁₂ and holoTC were associated with a 0.5-0.6% and 2.4-2.8% decrease in newborn DBS MMA, respectively; and a 10-nmol/L increase in first- and second-trimester maternal MMA and a 1-μmol/L increase in second-trimester tHcy with a 0.7-0.8% and 3% increase in newborn DBS MMA, respectively. Predictors of newborn DBS MMA concentration include maternal MMA concentration in both trimesters, first-trimester holoTC and second-trimester total B₁₂, hypertensive disorder of pregnancy, parity, newborn sex, newborn feeding following delivery, gestational age at birth and neonatal age at DBS collection. Further research in women at high risk of adverse birth outcomes, and the association between newborn MMA and functional outcomes is needed.

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