Association of maternal metabolic conditions with mitochondrial DNA copy number in cord blood

Mitochondrial dysfunction has been linked with metabolic disorders, given the central role of mitochondria in multiple crucial metabolic processes. However, little is known about how maternal metabolic conditions may affect mitochondrial function in newborns, although several other prenatal exposures have been associated with impaired mitochondrial function in either the placenta or cord blood. This study aimed to assess the association between maternal metabolic conditions and mitochondrial DNA copy number (mtDNA-CN, as a biomarker for mitochondrial function) in newborns.

Among 999 mother-newborn pairs from the Boston Birth Cohort, mtDNA-CN in newborn umbilical cord blood and maternal blood collected at delivery were measured by a targeted genome sequencing approach. Linear regressions were used to evaluate the association between maternal metabolic conditions (diabetes mellitus, pre-pregnancy obesity, and the combination of the two conditions) and mtDNA-CN Z-scores in cord blood. The models were initially adjusted for maternal and child demographic and lifestyle characteristics, followed by additional adjustment for maternal mtDNA-CN to explore its potential influence on the results.

In this sample, 23.6% of mothers had pre-pregnancy obesity, and 13.6% had diabetes. In models examining the two conditions separately, both maternal diabetes (Beta = 0.18, 95% CI: 0.00, 0.36, p = 0.054) and obesity (Beta = 0.10, 95% CI: -0.04, 0.25, p = 0.166) were associated with increased cord blood mtDNA-CN Z scores, but neither association reached statistical significance. When examined together, newborns whose mothers had both diabetes and pre-pregnancy obesity had statistically significantly higher cord mtDNA-CN Z scores (Beta = 0.35, 95% CI: 0.08, 0.63, p = 0.012) compared to newborns whose mothers did not have the two conditions. Further adjustment for maternal blood mtDNA-CN did not substantially alter the above associations.

Maternal diabetes and obesity jointly were associated with higher levels of cord blood mtDNA-CN. Future studies should further assess whether cord blood mtDNA-CN explains the link between maternal metabolic conditions and offspring health outcomes.