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Table 1 Summary table of articles included in this systematic review

From: Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence

First author

Year

Organism

Study type

Scale

Loci (if targeted)

Total sample size

Exposure pattern

Ethanol exposure time (gestational days)

DNA methylation analysis platform

Tissues

Wille-Bille

2020

Wistar Rats

Intervention

Targeted

Pdyn, Kor

32

Moderate

GD 17–20

Pyrosequencing

Ventral Tegmental Area (PDYN), Amygdala (KOR)

Alberry

2020

C57Bl/6 Mouse

Intervention

MWAS

-

21

Moderate

GD 0–21

MeDIP-Chip

Hippocampus

Abbott

2018

CD1 Mouse

Transgenerational

Global + Targeted

Id2 and Rzrβ promoters

195

Moderate-high

GD 0.5–19.5

MSP + ELISA

Rostral & Caudal regions of neocortex

Lussier

2018

Sprague–Dawley Rats

Intervention

MWAS

-

39

Moderate

GD 1–21

Bisulfite sequencing

Hippocampus, white blood cells

Marjonen

2018

C57Bl/6 J Mouse Rcc

Intervention

Targeted

Igf2/H19 imprinting control region (ICR), Igf2 DMR 1, Snrpn ICR, Peg3 ICR

10

Moderate

GD 0.5–8.5

MassARRAY EpiTYPER

Embryonal + placental

Lu

2018

Wistar Rats

Intervention

Targeted

Gad67

16

Unclear, possibly high

GD 9–20

Amplicon sequencing

Hippocampus

Wille-Bille

2018

Mouse

Intervention

Targeted

Pdyn, Kor

64

Moderate

GD 17–20

MSP

Ventral Tegmental Area, NAc (PDYN only), Prefrontal Cortex (KOR only)

Ozturk

2017

C57Bl/6 Mouse

Intervention

Global

-

18

Moderate

GD 7–16

ELISA

Neocortex

Zhou

2016

C57Bl/6 J Mouse

Intervention

Targeted

Igf2/H19, DMR0, DMR1, DMR2, H19 DMR

33

High

GD 0.5–15.5

MassARRAY EpiTYPER

Heart, brain, placental

Zhang

2015

C57Bl/6 Mouse

Intervention

Targeted

From -144 to -20 bp Slc17a6 transcription start site

109

Moderate

GD 0–8.5

Bisulfite sequencing

Hippocampus

Ngai

2015

Sprague–Dawley Rats

Intervention

Targeted

Nr3c1 and Slc6a4

18

Unclear

GD 1-? (possibly 20)

Pyrosequencing

Hippocampus, hypothalamus

Marjonen

2015

C57Bl/6 J Mouse Rcc

Intervention

Targeted

Six CpG islands in each of Olfr110, Vmn2r64, Vpreb2, Olfr601 and Hist1h2ai

18

Moderate

GD 0.5–8.5

Amplicon sequencing

Hippocampus, main olfactory epithelium

Gangisetty

2015

Fisher-344 Rats

Intervention

Targeted

D2r promoter

18

Moderate

GD 7–21

MSP + pyrosequencing

Pituatry gland

Gangisetty

2014

Sprague–Dawley Rats

Intervention

Targeted

Pomc

18

Moderate

GD 7–21

MSP

Mediobasal hypothalamus

Chen

2013

C57Bl/6 Mouse

Intervention

Global

-

17

Moderate-high

GD 7–16

Immunohistochemistry

Hippocampus

Laufer

2013

C57Bl/6 Mouse

Intervention

MWAS

-

12

Unclear

GD 0–10

MeDIP-Chip

Whole brain

Bekdash

2013

Sprague–Dawley Rats

Intervention

Targeted

Pomc

24

Moderate

GD 7–21

MSP

Mediobasal hypothalamus

Govorko

2012

Sprague–Dawley Rats

Transgenerational

Global + Targeted

Pomc

45

Moderate

GD 7–21

MSP + pyrosequencing + Immunohistochemistry

Brain

Downing

2011

C57BL/6 J (B6) Mouse

Intervention

Targeted

Igf2 DMR1, four CpG sites

45

High

GD 0–8.5

Amplicon sequencing

Embryonal + placental

Stouder

2011

Normal FVB/N Mouse

Intervention

Targeted

H19, Gtl2, Peg1, Srnpn, Peg3

38

Light

GD 10–18

Pyrosequencing + Amplicon Sequencing

Tail, liver, tibialis anterior muscle, hippocampus, whole brain, sperm

Kaminen-Ahola

2010

C57Bl/6 Mouse

Intervention

Global + Targeted

A(vy) allele

373

Moderate

GD 0.5–8.5

Bisulfite sequencing

Forebrain, tail

Haycock

2009

C57Bl/6 & CastEi Hybrid Mouse

Intervention

Targeted

Igf2/H19

10

High

GD 1.5 & 2.5

Bisulfite sequencing

Embryonal + placental

Murillo-Fuentes

2005

Wistar Rats

Intervention

Global

-

32

Moderate-high

GD 0–8.5

Tritiated thymidine incorporation

Blood, liver

Maier

1999

Harlan Sprague–Dawley Rats

Intervention

Targeted

Bdnf

9

High

Unclear, possibly GD 1–20

Restriction digest + Southern Blot

Olfactory bulbs

Valles

1997

Wistar Rats

Intervention

Targeted

Gfap

4

Unclear, possibly moderate

Presumably GD 1–20

Restriction digest + Southern Blot

Brain

Garro

1991

Swiss-Webster Mice

Intervention

Global

-

164

High

GD 9–11.5

Tritiated thymidine incorporation

Fetal

Okazaki

2021

Human

Case–control study

MWAS

Five epigenetic clocks

12

FASD

-

Illumina 450 Beadchip

Buccal, peripheral blood

Timms

2019

Human

Observational Cohort Study

MWAS

-

783

Unclear

Unclear

Illumina 450 Beadchip

Cord blood

Cobben

2019

Human

Case–control study

MWAS

-

138

FASD

-

Illumina 450 Beadchip

Whole blood

Sarkar

2019

Human

Case–control Study

Targeted

PER2, POMC

224

Moderate-high

Month of conception and/or before birth (study 1), throughout pregnancy (study 2)

MSP + pyrosequencing

Buccal

Lussier

2018

Human

Case–control study

MWAS

-

48

FASD

-

Illumina 450 Beachchip + pyrosequencing

Buccal

Frey

2018

Human

Observational Cohort Study

MWAS

-

156

Unclear

Last 8 weeks of pregnancy

Illumina 450 Beadchip

Buccal

Sharp

2018

Human

Meta-analysis

MWAS

-

3075

Multiple patterns assessed (low/moderate and binge)

Second/third trimester

Illumina 450 Beadchip

Cord blood

Marjonen

2017

Human

Case–control study

Targeted

IGF2/H19

75

Moderate-high

Likely throughout

MassARRAY EpiTYPER

Placenta

Portales-Casamar

2016

Human

Case–control study

MWAS

-

206

FASD

-

Illumina 450 Beachchip + pyrosequencing

Buccal

Fransquet

2016

Human

Observational Cohort Study

Targeted

DRD4 promoter

536

Multiple patterns assessed

Multiple patterns assessed

MassARRAY EpiTYPER

Buccal

Laufer

2015

Human

Case–control study

MWAS

-

23

FASD

-

Illumina 450 Beachchip + pyrosequencing

Buccal

Lee

2015

Human

Observational Cohort Study

Targeted

DAT, SERT, MeCP2

164

Multiple patterns assessed (light, moderate and binge)

Likely throughout

Restriction digest + MSP

Cord blood

Masemola

2015

Human

Case–control study

Targeted

H19 ICR, IG-DMR, KvDMR1, PEG3 DMR

533

FAS

Unclear/likely throughout

Pyrosequencing

Whole blood (all), buccal (cases only)

Azzi

2014

Human

Observational Cohort Study

Targeted

ZAC1

213

Unclear

Last 3 months of pregnancy

MSP

Cord blood, leukocytes

Jarmasz

2019

Human & Macaque Monkeys

Case–control study

Global

-

36

Variable

Variable

Immunohistochemistry

Brain

Loke

2018

Human

Observational Cohort Study

Global

-

187

Variable

Multiple patterns assessed

MassARRAY EpiTYPER

Placenta