Table 2.

Studies of genome-wide placental DNA methylation with pregnancy complications

Condition/criteria	Main findings	Reference(s)
Miscarriage (normal chromosomes)	More variable DNA methylation at imprinted genes and reduced global DNA methylation were reported in chromosomally normal miscarriages compared with elective terminations.	Pliushch et al. 2010; Yin et al. 2012; Hanna et al. 2013
Placental mesenchymal dysplasia (PMD)/ triploidy/ complete hydatidiform mole (CHM)	DNA methylation changes at imprinted DMRs consistent with excess paternal alleles (PMD, CHM, diandric triploidy) or maternal alleles (digynic triploidy) and at affected regions of the placenta.	Bourque et al. 2011; Yuen et al. 2011a
Trisomy	Global hypermethylation in trisomy 21 placentas. Widespread changes in trisomy 16 miscarriage and confined placental trisomy 16. The latter overlap changes with preeclampsia.	Jin et al. 2013; Tolmacheva et al. 2013; Blair et al. 2014
Preeclampsia	Widespread DNA methylation changes in early onset preeclampsia, much fewer changes in late-onset (less severe) preeclampsia. Changes in genes associated with syncytial trophoblast and/or cell adhesion (an important process in trophoblast differentiation and function) among many others.	Yuen et al. 2010; Jia et al. 2012; Blair et al. 2013; Anton et al. 2014
Intrauterine growth restriction (IUGR)/small for gestational age	Inconsistent results, largely focused on imprinted genes. Criteria for IUGR vary by study. Correlation between L1 methylation and birth weight reported.	Yuen et al. 2010; Banister et al. 2011; Ferreira et al. 2011; Koukoura et al. 2012; Wilhelm-Benartzi et al. 2012
Assisted reproductive technology	One study identified multiple CpG sites with lower DNA methylation in placentas of ART babies and another, no difference in DNA methylation at repetitive Alu, L1 or α-satellite repeat elements; no loss of imprinting identified at 25 imprinted genes in ART placentae versus spontaneously conceived.	Katari et al. 2009; Camprubi et al. 2013