We explored peroxisome proliferator‐activated receptor‐γ co‐activator 1α gene (PPARGC1A), peroxisome proliferator‐activated receptor‐γ gene (PPARG), and transcription factor A mitochondrial gene (Tfam) promoter DNA methylation in newborns between both extremes of abnormal fetal growth: Small (SGA) and large for gestational age (LGA) in relation to the mother's characteristics. We further sought for the association of rs9930506 variant at FTO gene and the promoter patterns of DNA methylation in the aforementioned genes, in relation to the offspring's birth weight. In a cross‐sectional study, 88 healthy pregnant women and their babies were included. According to the offspring birth weight, there were 57 newborns with appropriate weight for gestational age (AGA), 17 SGA, and 14 LGA. After bisulphite treatment of umbilical cord genomic DNA, a real‐time methylation‐specific PCR was used to determine the promoter methylation status in selected CpGs. Promoter methylated DNA/unmethylated DNA ratio, expressed as mean ± s.e., was 0.82 ± 0.15 (45% of alleles) for PPARGC1A, and 0.0044 ± 0.0006 (0.4% of alleles) for Tfam. PPARG promoter was almost 100% methylated in all samples. In univariate analysis, there was no association among characteristics of the newborn and gene promoter methylation. None of the maternal features were related with the status of promoter methylation, except for a positive correlation between maternal BMI and PPARGC1A promoter methylation in umbilical cord (Pearson correlation coefficient r = 0.41, P = 0.0007). Finally, FTO rs9930506 AA homozygous in the LGA group showed decreased levels of methylated PPARGC1A in comparison with AG + GG genotypes and AGA and SGA infants. In conclusion, our findings suggest a potential role of promoter PPARGC1A methylation in metabolic programming.

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

AimsOffspring of women with gestational diabetes (GD) have more macrosomia than newborns of normal mothers. We studied macrosomia frequency, possible pathogenesis, and main predictors of its appearance at different gestational ages.Materials and MethodsA total of 1870 pregnant women with GD were recruited in primary care centres and maternity hospitals in the Argentine provinces of Corrientes, Chaco, Buenos Aires, and in Buenos Aires City; 1088 completed gestation and delivered an infant. We collected clinical and metabolic data, personal and obstetric history, and gestational and delivery characteristics. Presence of macrosomia was analysed in the whole population, the entire pregnancy, and in each trimester of gestation. Data were statistically analysed and values were expressed as mean ± SD and percentages. The study protocol was approved by the Ethics Committee and all participants signed informed consent.ResultsMacrosomia was found in 12.9% of newborns and obesity in all mothers with no significant differences between mothers with/without macrosomic offspring. In early pregnancy, the main significant indicators of macrosomia were: history of dyslipidaemia (5.6% vs 1.2%, respectively) and macrosomia in previous pregnancies (27% vs 13%, respectively). However, the third trimester showed a significant combination of higher BMI, FBG, and triglycerides.ConclusionsOffspring of women with GD presented macrosomia in 12.9% of cases, maternal history of dyslipidaemia and macrosomia in previous pregnancies being early predictors. The combination of maternal obesity, FBG, and hypertriglyceridemia became significant during the last trimester of pregnancy.

We tested the hypothesis that leukocyte telomere length (LTL) is associated with birth weight in both extremes of abnormal fetal growth: small (SGA) and large for gestational age newborns (LGA). Clinical and laboratory variables of the mothers and the neonates were explored; 45 newborns with appropriate weight for gestational age (AGA), 12 SGA and 12 LGA were included. Whether the differences might be explained by variation in OBFC1 (rs9419958) and CTC1 (rs3027234) genes associated with LTL was determined. A significant association between birth weight and LTL was observed; LTL was significantly shorter in LGA newborns (1.01 ± 0.12) compared with SGA (1.73 ± 0.19) p < 0.005, mean ± SE. Maternal (Spearman R = −0.6, p = 0.03) and neonatal LTL (R = −0.25, p = 0.03) were significantly and inversely correlated with maternal history of arterial hypertension in previous gestations. Neonatal LTL was not significantly associated with either rs9419950 or rs3027234, suggesting that the association between neonatal LTL and birth weight is not influenced by genetic variation in genes that modify the interindividual LTL. In conclusion, telomere biology seems to be modulated by abnormal fetal growth; modifications in telomere length might be programmed by an adverse environment in utero.

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