ESPE Yearbook of Paediatric Endocrinology

Medicine (Baltimore). 2020 Sep 25;99(39):e22389. doi: 10.1097/MD.0000000000022389. PMID: 32991460.

In this relatively small study (6 placenta) the placentas from mothers of infants born large for gestational age (LGA) were compared to placentas of appropriate gestational age (AGA) infants for changes in genome wide DNA methylation. There were significant differences in the specific methylation patterns between the two groups of placenta. The changes included hypo and hypermethylation of a large number of genes with different patterns of methylation on different chromosomes. The differentially methylated genes were involved in diverse biological functions such as ion binding, protein binding and cell-to-cell signaling, adhesion, transport, as well as system development and function. Network analysis of these genes identified pathways linked to possible risk of metabolic disease.

LGA infants are born to mothers with gestational diabetes, maternal obesity and sometimes to normal weight pregnant women. LGA infants have an adverse cardio-metabolic profile during childhood which gets worse during adolescence. The underlying mechanisms for the adverse cardio-metabolic profile are unknown but might involve defects in placental function. As environment and lifestyle are known to impact an individual’s DNA methylation pattern, the authors of this study hypothesized that LGA might correlate with changes in the placental DNA methylation and allow the expression of genes which confer the risk of developing metabolic disease. There are limited studies on placental methylation changes in LGA infants with studies mostly focusing on small for gestational age infants.

The current findings suggest that the intrauterine environment seems to alter the methylation status of some placental genes in LGA infants. However, how this then translates to obesity and metabolic syndrome later in life needs further study.