Abstract
Umbilical cord blood is frequently used in health monitoring of the neonate. Results may be affected by the proportion of arterial and venous cord blood, the venous blood coming from the mother to supply oxygen and nutrients to the infant, and the arterial carrying waste products from the fetus. Here, we sampled arterial and venous umbilical cords separately from 48 newly delivered infants and examined plasma metabolomes using GC-MS/MS metabolomics. We investigated differences in metabolomes between arterial and venous blood and their associations with gestational length, birth weight, sex, and whether the baby was the first born or not, as well as maternal age and BMI. Using multilevel random forest analysis, a classification rate of 79% was achieved for arteriovenous differences (p = 0.004). Several monosaccharides had higher concentrations in the arterial cord plasma while amino acids were higher in venous plasma, suggesting that the main differences in the measured arterial and venous plasma metabolomes are related to amino acid and energy metabolism. Venous cord plasma metabolites related to energy metabolism were positively associated with parity (77% classification rate, p = 0.004) while arterial cord plasma metabolites were not. This underlines the importance of defining cord blood type for metabolomic studies.
Highlights
In the fetal circulation, blood circulates through the placenta to exchange gases, nutrients, and metabolites with the maternal blood through passive diffusion and active transport over the placental membranes [1,2]
We observed systematic differences between the arterial and venous umbilical cord plasma metabolomes, primarily concerning energy metabolism. This suggests that the choice of arterial, venous, or mixed umbilical cord blood could have implications for research questions involving metabolic regulation, especially regarding energy and amino acid metabolism
The use of mixed, arterial, or venous cord blood could contribute to difficulties when trying to compare studies, especially given the potential for differing proportions of arterial and venous blood in mixed cord blood samples
Summary
Blood circulates through the placenta to exchange gases, nutrients, and metabolites with the maternal blood through passive diffusion and active transport over the placental membranes [1,2]. The venous umbilical cord blood (from the placenta to the fetus) is rich in oxygen and supplies the fetus with nutrients necessary for survival and growth [3]. Umbilical cord blood may be sampled directly after delivery before the cord is severed (e.g., to screen arterial and venous pH as well as blood gas analysis for early signs of acidosis [5] and for collecting blood spots for diagnosis of inborn errors of metabolism). Umbilical cord blood may be sampled to predict and assess neonatal health problems such as hypoxic-ischaemic encephalopathy [6], intrauterine growth restriction [7] and preeclampsia [8] or to prospectively predict childhood diseases (e.g., type 1 diabetes) [9]. Venous and arterial umbilical blood may be sampled separately using a syringe inserted into the respective blood vessel [7,10], but as this can be time consuming, frequently the blood is squeezed out from the cord after it is severed, resulting in the collection of a mixture of arterial and venous cord blood in unspecified proportions [11,12,13]
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