Epigenetic Dysregulation of Insulin-Like Growth Factor (IGF)-Related Genes and Adverse Pregnancy Outcomes: A Systematic Review

Objectives: Preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) are leading causes of neonatal mortality and morbidity around the world. Epigenetic alterations of the human genome may be involved in the causal chain of adverse pregnancy outcomes. In this systematic review we investigated whether PTB, LBW and SGA are associated with epigenetic dysregulation of insulin-like growth factor-related genes (IGF). Methods: We searched MEDLINE and EMBASE for peer-reviewed articles about IGF and PTB, LBW and SGA published up to February 2015. Two independent reviewers selected original, controlled, human studies published in any language and graded them using the Newcastle–Ottawa Quality Assessment Scale. Disagreements were resolved by consensus with a third reviewer. Results: Eighteen observational studies of low-to-moderate quality met the eligibility criteria out of 210 unique studies. There was substantial heterogeneity across studies. Most studies reported no, limited or borderline association between epigenetic changes (methylation or imprinting) of IGF-related genes and LBW or SGA. There were no IGF-related epigenetic studies of PTB. Conclusions: Overall, evidence of an association between epigenetic abnormalities of IGF-related genes and LBW or SGA was weak and inconsistent. Methodological concerns limited results validity.