Integrative Review of Genetic Factors Influencing Neurodevelopmental Outcomes in Preterm Infants

Biol Res Nurs. 2016 Mar;18(2):127-37. doi: 10.1177/1099800415605379. Epub 2015 Sep 15.


Preterm infants are at elevated risk for a host of neurodevelopmental problems, including disorders that appear later in life. Gene-environment interactions and prematurity may combine to increase the risk for poor neurodevelopmental outcomes. Increasing evidence supports a genetic link to risk for atypical development; however, no genomic risk profiles are currently used for infants without apparent genetic disorders. The purpose of this review was to synthesize recent evidence of genetic associations with atypical neurodevelopmental outcomes that may affect preterm infants who do not have a rare genetic disease. Electronic and hand-search strategies were used to find relevant articles that were English-language, peer-reviewed primary research or meta-analysis reports published between July 2009 and July 2014, involving human participants. Articles included in the analysis (N = 29) used a wide range of study designs and methodologies, complicating the analysis. An integrative-review design was used to synthesize the data. Numerous genes (n = 43) and additional large deletion copy number variants were associated with neurodevelopmental outcomes, including cognition, attention, perception, psychiatric disease, autism spectrum disorder, cerebral palsy, infant behavior, and alterations in brain architecture. The creation of genetic risk profiles for complex disorders of neurodevelopment is presently hindered by inconsistent genetic-association evidence, methodological considerations, reporting problems, and lack of replication. However, several avenues of investigation offer promise, including large (>100 kb) copy number variants and the candidate genes MET, NRG3, and SLC6A4, each of which were reported to have associations with neurodevelopmental outcomes in multiple, high-quality studies.

Keywords: cognition; genetics; genomics; neurodevelopment; prematurity; preterm infant.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Developmental Disabilities / genetics*
  • Female
  • Gene-Environment Interaction
  • Humans
  • Infant, Newborn
  • Infant, Premature / growth & development*
  • Male
  • Neurodegenerative Diseases / genetics*