Table 3.

DNA methylation changes that are associated with fetal growth in the human placenta.

Suspected Contributor	Growth Status	Gene/Locus	Hypo/Hypermethylated Compared to Normal Growth Placenta	References
	Intrauterine growth restriction (IUGR) Small for gestational age (SGA)	ALDH3B2, OAT, CSTA, KLHL5, GPR4, MFAP1, DNAJB4, NCOA4, GYS2, GIMAP2, C20orf28, FGF14, GGPS1, NFKBIZ	Hypomethylated	[66]
	IUGR/SGA	APBA2, RPE65, SLC25A18, SERPINA5, MEP1A, PDC, OMG, CHML	Hypermethylated
	SGA	IGF2	Hypomethylation with decreased expression	[67]
	IUGR	IGF2	Hypomethylation with decreased expression	[68]
	SGA	H19	Hypomethylation	[67]
	IUGR	IGF2/H19	Hypomethylation of the region with a decrease in expression of IGF2	[69]
	IUGR	SERPINA3	Hypomethylation with increased expression	[70]
Maternal smoking	Low birth weight	CYP1A1	Lower methylation of this locus is correlated with maternal smoking and these maternal smokers had lower-weight infants but no direct correlation between hypomethylation at this locus for low-birth-weight infants	[61]
	Weight gain during the first year	MEG3 promotor for DLK-1DIO3 imprinted region	Hypomethylation of this promotor is negatively correlated with weight increase during the first year of life	[71]
Preeclampsia	IUGR + preeclampsia	D-loop (mitochondrial DNA)	Lower methylation levels decreased for IUGR/Pre-eclampsia pregnancies	[72]
	IUGR	Metabolic genes—PCKSKIN, KCNAB2, BLK, PTRN2, GK, GFPTI, AGMO, RPH3AL Cardiovascular—PTGIR, NTSRI, ACE, NPY, NOS3, CASZI Inflammatory—IL10, CD28, AZUI, IL3RA, MARCH1, LRBA, CD38, IL32	Differentially methylated between placenta of IUGR and AGA infants	[73]
	Reduced fetal growth	HSD11B2	Hypermethylation has been associated with reduced fetal growth	[74]
	Fetal growth restriction (FGR)	IGF2, AHRR	Hypomethylation in one position of each locus in FGR placenta	[75]
	FGR	HSD11B2, WNT2	Hypermethylation of these locus in FGR	[75]
Maternal asthma	Low-weight infants	AURKA	Hypermethylation of this locus correlated with lower fetal height and weight	[60]
	SGA	RTL1	Increased methylation in cytosine paired to guanine 1 (CpG1) of the gene	[76]
	Severe SGA	RTL1	Very high methylation in CpG1 of the gene
	SGA	ATG2B, NKX6.1,SLC13A5	Hypermethylated in SGA placenta correlated with inverse relationship to gene expression changes	[77]
	SGA	WNT2	High promotor methylation	[78]
Early- and late-onset preclamspia	SGA	FN1, PKM2, KRT15	Differential methylation	[54]