TABLE 1.
Included studies
| First author | Year | Proposed instrument(s) | Exposure | Outcome |
|---|---|---|---|---|
| Allard 62 | 2015 | 2 step a : glucose genetic risk score (GRS), methylation GRS | 2 step: maternal fasting glucose, methylation | 2 step: methylation, cord blood leptin |
| Alwan 63 | 2012 | C282Y | Iron | Blood pressure, waist circumference, body mass index (BMI) |
| Bech 64 | 2006 | NAT2, CYP1A2, GSTA1 | Caffeine | Stillbirth |
| Bedard 65 | 2018 | maternal 12 SNP weighted GRS | Haemoglobin | Wheezing, asthma, atopy, low lung function |
| Bernard 66 | 2018 | 8 FADS variants | Omega 3 and omega 6 polyunsaturated fatty acids | Gestational duration, birthweight, birth length |
| Binder 67 | 2013 | MTHFR rs1801133, rs1801131 | Folate | Genome‐wide methylation |
| Bonilla 68 | 2012 | GRS | Fasting glucose, type 2 diabetes | Intelligence quotient (IQ) at age 8 |
| Bonilla 69 | 2012 | rs492602, rs1801198, rs9606756 | Vitamin B12 | IQ at age 8 |
| Caramaschi 70 | 2017 | 2 step: rs492602, rs1047781 for vitamin b12; rs5750236, rs1890131 for methylation | 2 step: vitamin B12, methylation | 2 step: methylation, IQ |
| Caramaschi 71 | 2018 | rs1051730 | Smoking heaviness | Autism spectrum disorder |
| Evans 72 | 2018 | 403 SNP GRS | Maternal type 2 diabetes | Birthweight |
| Geng 73 | 2018 | 35, 25, and 41 SNP GRS | Waist‐to‐hip ratio adjusted for BMI, hip circumference adjusted for BMI, waist circumference adjusted for BMI | Birthweight, birth length, head circumference |
| Granell 74 | 2008 | MTHFR C677T | Folate | Atopy, asthma |
| Howe 75 | 2019 | rs1229984 | Alcohol | Facial morphology |
| Humphriss 76 | 2013 | ADH1B rs1229984 | Alcohol | 3 composite balance scores (dynamic balance, static balance eyes open, static balance eyes closed) |
| Hwang 77 | 2019 | 96, 82, and 60 SNP GRS | High‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, triglycerides | Birthweight |
| Korevaar 78 | 2014 | GRS | Thyroid‐stimulating hormone (TSH), free thyroxine (FT4) | Soluble fms‐like tyrosine kinase‐1 (sFlt1), placental growth factor (PlGF) |
| Lawlor 79 | 2008 | FTO | BMI | Fat mass at age 9‐11 |
| Lawlor 21 | 2017 | GRS | BMI | BMI, fat mass index |
| Lee 80 | 2013 | MTHFR C677T | Homocysteine | Birthweight |
| Lewis 81 | 2009 | MTHFR C677T | Folate intake | Total weight, total body fat mass, total lean mass |
| Lewis 82 | 2012 | 10 SNPs in ADH4, ADH1A, AHD1B, ADH7 (rs4699714, rs3763894, rs4148884, rs2866151, rs975833, rs1229966, rs2066701, rs4147536, rs1229984, rs284779) | Alcohol | IQ at age 8 |
| Lewis 83 | 2014 | GRS based on rs1799945, rs1800562, rs4820268 | Iron | IQ at age 8 |
| Mamasoula 84 | 2013 | MTHFR rs1801133 | Folate | Congenital heart disease |
| Morales 85 | 2011 | rs1205 | C‐reactive protein (CRP) | Wheezing, lower respiratory tract infection |
| Morales 86 | 2016 | rs1983204, rs344008, rs6795327, rs7637701, rs11929637 | Methylation at top‐ranked cpg site for placental methylation in smokers | Birthweight |
| Murray 87 | 2016 | GRS including ADH1A rs2866151, rs975833, AHD1B rs4147536, ADH7 rs284779 | Alcohol | Conduct problem trajectories (6 measures of Strengths and Difficulties Questionnaire) |
| Richmond 88 | 2016 | GRS | BMI | HIF3A methylation |
| Richmond 89 | 2017 | GRS | BMI | BMI, fat mass index |
| von Hinke Kessler Scholder 90 | 2014 | ADH1B rs1229984 | Alcohol | Academic achievement (KS1,KS2,KS3, GCSE) |
| Shaheen 91 | 2014 | ADH1B rs1229984 | Alcohol | Childhood atopic disease |
| Steenweg‐de Graaff 92 | 2012 | MTHFR C677T | Folate | Emotional and behavioural score (Child Behaviour Checklist) |
| Steer 93 | 2011 | MTHFR C677T | Folate | Bone mineral content, bone mineral density, bone area |
| Taylor 94 | 2014 | rs1051730 | Smoking | Latent class of offspring smoking initiation |
| Thompson 95 | 2019 | Separate 7 SNP GRS | Vitamin D, calcium | Birthweight |
| Tyrrell 96 | 2016 | GRS | BMI, fasting glucose, diabetes, triglycerides, HDL, blood pressure, vitamin D, adiponectin | Birthweight |
| Wehby 97 | 2011 | 14 SNPs | Smoking | Birthweight |
| Wehby 98 | 2011 | 4 SNPS (rs1435252, rs1930139, rs1547272, rs2743467) | Smoking | Orofacial cleft |
| Wehby 99 | 2013 | smoking: rs12914385, rs1051730, alcohol: ADH1B rs1229984, BMI: rs8050136 | Smoking, alcohol use, obesity | Birthweight |
| Yajnik 100 | 2014 | MTHFR rs1801133 | Homocysteine | Birthweight |
| Zerbo 101 | 2016 | rs3116656, rs2794520 | CRP | Autism spectrum disorder |
| Zhang 102 | 2015 | GRS | Maternal height | Birth length, birthweight |
| Zuccolo 103 | 2013 | rs1229984 | Alcohol (1st trimester) | IQ at age 8, educational attainment |
a
2 step Mendelian randomisation designs are a specific subtype of Mendelian randomisation designs proposed to investigate mediation of the relationship between maternal exposures and offspring outcomes by offspring DNA methylation, under additional strong assumptions. 104 In this approach, maternal genetic variants are proposed as instruments for the effect of maternal exposures on offspring methylation across all measured sites. For any methylation sites where a non‐null effect was detected for any individual in the population, offspring genetic variants associated with methylation at that site are then proposed as instruments for the effect of methylation at that site on offspring outcomes.