Epigenetic modifications of human placenta associated with preterm birth: a systematic review

Preterm birth (PTB) is one of the leading causes of neonatal mortality and morbidity around the world. Epigenetic alterations of the human placenta may be involved in the causal chain of adverse pregnancy outcomes specifically PTB. In this systematic review, we investigated whether epigenetic dysregulation of the human placenta is associated with PTB.

We searched MEDLINE and EMBASE and systematically reviewed all relevant studies on epigenetic placental modifications in PTB. Two independent reviewers selected controlled human studies published in any language, evaluated their quality, and graded them using the Newcastle-Ottawa Quality Assessment Scale. We resolved disagreements by consensus with a third reviewer.

Eleven observational studies of low to moderate quality met the eligibility criteria out of 60 unique studies. Most studies reported an association between placental epigenetic changes (methylation, mRNA and miRNA) and PTB, although research methods were highly heterogeneous.

Studies reported various associations between specific epigenetic findings and PTB, although methodological concerns limited results' validity. Additional high quality studies are needed to assess the repeatability of these findings. The STROBE guidelines can be used to improve the quality of reporting.