(P10-055-24) Deep Metabolic Phenotyping of Newborn Cord Blood Reveals Maternal-Fetal Interactions and Diet-Disease Associations

Objectives: Pregnant mothers use metabolites that cross the placenta to provide energy, structural components, essential nutrients, and signals to the developing fetus. However, fetal availability and absorption of many critical metabolites have not been investigated in healthy or diseased states; and associations between microbial metabolites and disease have not been thoroughly investigated. In our study, we addressed these shortcomings of fetal metabolic knowledge to better understand fetal metabolic exposure and its consequences.

Methods: We collected arterial and venous plasma from 536 umbilical cords at Lucile Packard Children’s Hospital. We then performed untargeted metabolomics and targeted lipidomics using a biphasic separation capturing the aqueous and organic phases. We obtained complete electronic health records for mother and newborn using the Stanford Research Repository, which included diagnoses, drugs administered, and labs performed on mother and infant.

Results: In our cohort, 185 compounds had a significantly higher concentration in the venous blood compared to arterial blood, indicating utilization by the fetus. The most significant class of these metabolites is energy molecules, including glucose and many fatty acids. The most significant fatty acid was linoleic, acid an essential fatty acid. 

The microbial metabolite 3-indolepropionic acid is lower in newborns receiving benzodiazepines (used for neural conditions; OR = -1.81), suggesting it has a healthy effect. Meanwhile, hydroxyhippurate, which is produced by Clostridium, positively associated with neonatal respiratory distress syndrome, neonatal jaundice associated with prematurity, and feeding problems of the newborn (ORs = 1.88, 1.82, 1.55).

We also discovered a metabolic signature of a healthy baby denoted by the diagnosis: encounter for routine child health examination without abnormal findings. This “newborn health signature” had higher levels of vitamin B5, diet-derived tryptophan betaine, and triglycerides, among other metabolites and lipids.

Conclusions: Dietary decisions made by pregnant mothers impact the metabolites reaching the developing fetus. These metabolites are associated with profound health effects on the newborn baby.

Funding Sources: Stanford Genetics, Stanford Pediatrics, Stanford MCHRI