Inverse associations of cord blood mitochondrial DNA copy number with childhood adiposity.

OBJECTIVE: The objective of this study was to examine associations between umbilical cord mitochondrial DNA copy number (mtDNAcn) and adiposity across childhood. METHODS: In a prospective birth cohort of Dominican and African American children from New York City, New York (1998-2006), mtDNAcn was measured in cord blood. Children (N = 336) were evaluated for their height, weight, and bioimpedance at age 5, 7, 9, and 11 years. We used linear mixed-effects models to assess associations of mtDNAcn tertiles in cord blood with child BMI, BMI z scores, fat mass index, and body fat percentage. Latent class growth models and interactions between mtDNAcn and child age or child age2 were used to assess associations between age and adiposity trajectories. RESULTS: BMI was, on average, 1.5 kg/m2 higher (95% CI: 0.58, 2.5) in individuals with mtDNAcn in the low- compared with the middle-mtDNAcn tertile. Results were similar for BMI z score, fat mass index, and body fat percentage. Moreover, children in the low-mtDNAcn group had increased odds of being in an "increasing" or "high-stable" adiposity class. CONCLUSIONS: Lower mtDNAcn at birth may predict greater childhood adiposity, highlighting the potential key role of perinatal mitochondrial function in adiposity during development.

Mitochondrial DNA copy number dynamics and associations with the prenatal environment from birth through adolescence in a population of Dominican and African American children.

Mitochondrial DNA copy number (mtDNAcn) dynamics throughout childhood are poorly understood. We profiled mtDNAcn from birth through adolescence and evaluated how the prenatal environment influences mtDNAcn across childhood. Data were collected from children from New York City followed through 18 years. Using duplexed qRT-PCR, we quantified mtDNAcn relative to nuclear DNA in blood collected from the umbilical cord (n = 450), children aged 5-7 (n = 510), and adolescents aged 15-18 (n = 278). We examined mtDNAcn across childhood with linear mixed-effects models (LMM). Relative mtDNAcn was lowest at birth (mean ± SD: 0.67 ± 0.35) and increased in childhood (1.24 ± 0.50) then slightly declined in adolescence (1.13 ± 0.44). We observed no differences in mtDNAcn by sex or race/ethnicity. mtDNAcn was positively associated with prenatal environmental tobacco smoke exposure (0.077 [ 0.01, 0.14] change in relative mtDNAcn) but negatively associated with maternal completion of high school (-0.066 [-0.13, 0.00]), with the receipt of public assistance at birth (-0.074 [-0.14, -0.01]), and when mother born outside the U.S (-0.061 [-0.13, 0.003]). Infant birth outcomes were not associated with mtDNAcn. MtDNAcn levels were dynamic through childhood and associated with some prenatal factors, underscoring the need for the investigation of longitudinal mtDNAcn for human health research.