Gestational overgrowth and undergrowth affect neurodevelopment: similarities and differences from behavior to epigenetics

Int J Dev Neurosci. 2013 Oct;31(6):406-14. doi: 10.1016/j.ijdevneu.2012.11.006. Epub 2012 Nov 28.


The size of an infant at birth, a measure of gestational growth, has been recognized for many years as a biomarker of future risk of morbidity. Both being born small for gestational age (SGA) and being born large for gestational age (LGA), are associated with increased rates of obesity and metabolic disorder, as well as a number of mental disorders including attention deficit/hyperactivity disorder, autism, anxiety, and depression. The common risks raise the question of what neurobiological mechanisms are altered in SGA and LGA offspring. Here we review recent findings allowing for direct comparison of neurobiological outcomes of SGA and LGA in human and animal models. We also present new data highlighting similarities and differences in behavior and neurobiology in our mouse models of SGA and LGA. Overall, there is significant data to support aberrant epigenetic mechanisms, particularly related to DNA methylation, in the brains of SGA and LGA offspring, leading to disruptions in the cell cycle in development and gene expression in adulthood.

Keywords: ADHD; BDNF; CNS; DA; DAT; DNA methylation; Dopamine; GWG; HF; IUGR; Intrauterine growth restriction; LGA; LP; MOR; Macrosomia; Mesolimbic; NAc; Opioid; PENK; PFC; PI3K; SGA; TH; VTA; attention deficit/hyperactivity disorder; brain-derived neurotrophic factor; central nervous system; dopamine; dopamine transporter; gestational weight gain; high-fat; intrauterine growth restriction; large for gestational age; low-protein; mu-opioid receptor; nucleus accumbens; phosphoinositide 3-kinase; prefrontal cortex; preproenkephalin; small for gestational age; tyrosine hydroxylase; ventral tegmental area.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Body Weight
  • Developmental Disabilities*
  • Epigenesis, Genetic
  • Epigenomics*
  • Humans
  • Infant, Small for Gestational Age*
  • Mice