Objective: To investigate whether mitochondrial DNA (mtDNA) content may be associated with clinical features, anthropometric variables, and laboratory findings in both extremes of abnormal fetal growth: small and large size for gestational age.

Research Methods and Procedures: Eighty‐eight pregnant women and their infants were included in a cross‐sectional study. According to the offspring birthweight, normalized by sex and gestational age, there were 57 newborns with appropriate weight for gestational age (AGA) and 31 with abnormal weight for gestational age: 17 small for gestational age (SGA) and 14 large for gestational age (LGA). mtDNA quantification using nuclear DNA as a reference was measured by a real‐time quantitative polymerase chain reaction method.

Results: The mothers’ pregestational BMI was associated with the weight of their offspring: SGA infants had lean mothers (BMI, 21.4 ± 0.7), and LGA infants had overweight mothers (BMI, 26.7 ± 1.4) in comparison with AGA infants (BMI, 23.0 ± 0.7) (p < 0.003). Newborn leptin levels were associated with birthweight after adjustment for sex and gestational age (SGA, 7.0 ± 1.1 ng/mL; AGA, 15.2 ± 1.6 ng/mL; and LGA, 25.6 ± 4.1 ng/mL) (p < 0.002). Conversely, mtDNA/nuclear DNA ratio was significantly lower in both extremes of abnormal fetal growth, SGA (18 ± 6) and LGA (9 ± 2), at birth in comparison to AGA‐weight infants (28 ± 4) (p < 0.03).

Discussion: Our findings show that mtDNA content is decreased in newborns with abnormal weight in comparison with AGA infants. On the basis of a cumulative body of evidence, we speculate that mtDNA depletion is one of the putative links between abnormal fetal growth and metabolic and cardiovascular complications in later life.