Low alcohol consumption and pregnancy and childhood outcomes: time to change guidelines indicating apparently ‘safe’ levels of alcohol during pregnancy? A systematic review and meta-analyses

Mamluk, Loubaba; Edwards, Hannah B; Savović, Jelena; Leach, Verity; Jones, Tim; Moore, Theresa Hm; Ijaz, Sharea; Lewis, Sarah J.; Donovan, Jenny; Lawlor, Debbie A.; Smith, George Davey; Fraser, Abigail; Zuccolo, Luisa

doi:10.1136/bmjopen-2016-015410

Cited by 144 publications

(137 citation statements)

References 52 publications

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“…Many studies have shown that alcohol consumption during pregnancy has increased worldwide. [17][18][19] Notably, alcohol consumption during pregnancy has been found to cause CHD in foetuses. 20,21 However, the mechanistic link between alcohol and CHD is still largely unclear.…”

Section: Discussionmentioning

confidence: 99%

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

Peng

Han

Chang

et al. 2019

J Cellular Molecular Medi

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Alcohol consumption during pregnancy can cause foetal alcohol syndrome and congenital heart disease. Nonetheless, the underlying mechanism of alcohol‐induced cardiac dysplasia remains unknown. We previously reported that alcohol exposure during pregnancy can cause abnormal expression of cardiomyogenesis‐related genes, and histone H3K9me3 hypomethylation was observed in alcohol‐treated foetal mouse heart. Hence, an imbalance in histone methylation may be involved in alcohol‐induced cardiac dysplasia. In this study, we investigated the involvement of G9α histone methyltransferase in alcohol‐induced cardiac dysplasia in vivo and in vitro using heart tissues of foetal mice and primary cardiomyocytes of neonatal mice. Western blotting revealed that alcohol caused histone H3K9me3 hypomethylation by altering G9α histone methyltransferase expression in cardiomyocytes. Moreover, overexpression of cardiomyogenesis‐related genes (MEF2C, Cx43, ANP and β‐MHC) was observed in alcohol‐exposed foetal mouse heart. Additionally, we demonstrated that G9α histone methyltransferase directly interacted with histone H3K9me3 and altered its methylation. Notably, alcohol did not down‐regulate H3K9me3 methylation after G9α suppression by short hairpin RNA in primary mouse cardiomyocytes, preventing MEF2C, Cx43, ANP and β‐MHC overexpression. These findings suggest that G9α histone methyltransferase‐mediated imbalance in histone H3K9me3 methylation plays a critical role in alcohol‐induced abnormal expression cardiomyogenesis‐related genes during pregnancy. Therefore, G9α histone methyltransferase may be an intervention target for congenital heart disease.

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Section: Discussionmentioning

confidence: 99%

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

Peng

Han

Chang

et al. 2019

J Cellular Molecular Medi

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“…It is well established that heavy alcohol use in pregnancy can cause foetal alcohol syndrome (Mukherjee, Hollins, & Turk, 2006), resulting in physical and cognitive impairments (Coles, Platzman, Lynch, & Freides, 2002;Gibbard, Wass, & Clarke, 2003;Guerri, Bazinet, & Riley, 2009). However, even at levels of alcohol consumption below that required for foetal alcohol syndrome, exposure to alcohol during gestation has been shown to be associated with detrimental outcomes in the offspring, such as being small for gestational age (Mamluk et al, 2017), and birth complications such as pre-eclampsia and placental abruption (Salihu et al, 2011), as well as behavioural outcomes such as increased risk of externalising disorders (Sayal et al, 2014) and internalising disorders (Sood et al, 2001;Walthall, O'Connor, & Paley, 2008). However, much research in this area has been conducted on Intrauterine alcohol and depression 4 offspring at an early age, with less research in older age groups to establish whether these associations persist into adulthood.…”

Section: Introductionmentioning

confidence: 99%

Association of intrauterine alcohol exposure and offspring depression: A negative control analysis of maternal and partner consumption

Easey

Timpson

Munafò

2018

Preprint

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Background: Previous research has suggested that intrauterine alcohol exposure is associated with a variety of adverse outcomes in offspring. However, few studies have investigated its association with offspring internalising disorders in late adolescence. Methods:Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the associations of maternal drinking in pregnancy with offspring depression at age 18. We also examined partner drinking as a negative control for intrauterine exposure for comparison. Results:Offspring of mothers that consumed any alcohol at 18 weeks gestation were at increased risk of having a diagnosis of depression (OR 1.15, 95% CI 1.00 to 1.32), but there was no clear evidence of association between partners alcohol consumption during pregnancy and increased risk of offspring depression (OR 0.90, 95% CI 0.78 to 1.04). Conclusions:Maternal drinking in pregnancy was associated with increased risk of offspring depression at age 18. Residual confounding may explain this association, but the negative control comparison of paternal drinking provides some evidence that it may be causal, and this warrants further investigation. Intrauterine alcohol and depression3 Association of intrauterine alcohol exposure and offspring depression:A negative control analysis of maternal and partner consumption 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

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“…Individuals exposed to low to moderate levels of alcohol do not typically present with facial, anthropometric or cognitive abnormalities. Indeed, a large systematic review found weak evidence of adverse effects from low to moderate alcohol exposure 7 However, previous research has suggested that low to moderate alcohol exposure may have modest adverse effects on offspring cognition and school performance 8; 9 and sub-clinical facial differences have been observed between low to moderately exposed, and unexposed individuals 10 . Variation (within the normal range) in facial morphology may be a marker of alcohol-related cognitive impairments; children exposed to alcohol with more FAS like facial symptoms have been shown to perform worse on psychometric tests 11 .…”

Section: Introductionmentioning

confidence: 99%

Prenatal alcohol exposure and facial morphology in a UK cohort

Howe

Sharp

Hemani

et al. 2018

Preprint

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High levels of prenatal alcohol exposure are known to cause an array of adverse outcomes including foetal alcohol syndrome (FAS); however, the effects of low to moderate exposure are less-well characterised. Previous findings suggest that differences in normal-range facial morphology may be a marker for alcohol exposure and related adverse effects. Therefore, in the Avon Longitudinal Study of Parents and Children, we tested for an association between maternal alcohol consumption and six FAS-related facial phenotypes in their offspring, using both self-report questionnaires and the maternal genotype at rs1229984 in ADH1B as measures of maternal alcohol consumption. In both self-reported alcohol consumption (N=4,233) and rs1229984 genotype (N=3,139) analyses, we found no strong statistical evidence for an association between maternal alcohol consumption and facial phenotypes tested. The directions of effect estimates were compatible with the known effects of heavy alcohol exposure, but confidence intervals were largely centred around zero. We conclude that, in a sample representative of the general population, there is no strong evidence for an effect of prenatal alcohol exposure on normal-range variation in facial morphology.We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

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Low alcohol consumption and pregnancy and childhood outcomes: time to change guidelines indicating apparently ‘safe’ levels of alcohol during pregnancy? A systematic review and meta-analyses

Cited by 144 publications

References 52 publications

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

Association of intrauterine alcohol exposure and offspring depression: A negative control analysis of maternal and partner consumption

Prenatal alcohol exposure and facial morphology in a UK cohort

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