Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa)

Abstract

Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999–2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

Adolescence and the next generation

“…Although there are fewer human studies, alcohol consumption of more than two standard drinks per day is linked to morphological changes in sperm 60 . One report of a very large study has found effects of heavy (more than five standard drinks per day) paternal but not maternal preconception drinking on offspring head circumference and risk of microcephaly 61 . Paternal obesity generates risks of metabolic disturbance and obesity in offspring through the gamete epigenome, but diet and exercise appear to modify these risks 62,63 .…”

The causal web of foetal alcohol spectrum disorders: a review and causal diagram

“…Nevertheless, on average, binge and heavy chronic patterns of maternal alcohol use are most likely to result in FASD [29][30][31][32][33][34]. Evidence on the effects of low to moderate PAE on developmental outcomes is limited and inconsistent, ranging from evidence of harm, to no effect, to evidence of slight benefit [35][36][37][38][39][40][41][42][43][44]. For example, Kelly et al found that 3-year-old boys who were born to mothers who reported drinking no more than one to two units of alcohol per week or per occasion during pregnancy had a lower risk of hyperactivity and conduct problems than those born to abstainers [40].…”

“…For example, Kelly et al found that 3-year-old boys who were born to mothers who reported drinking no more than one to two units of alcohol per week or per occasion during pregnancy had a lower risk of hyperactivity and conduct problems than those born to abstainers [40]. Negative control studies that compare the strength of association for maternal and paternal exposures have also been used to investigate the causal effects of low to moderate PAE, but did not find evidence of intrauterine effects on child IQ or head circumference [41,42]. In contrast, Mendelian randomisation studies have offered evidence that low to moderate PAE can cause persistent conduct problems and adversely affect cognitive and academic outcomes [37,38,43].…”

Maternal alcohol consumption during pregnancy and offspring epigenome-wide DNA methylation: findings from six general population-based birth cohorts

“…Firstly, we found low inter-study heterogeneity for most of our CpG sites – if there was a prominent interaction between alcohol (a folate antagonist) and folate (a methyl donor), then we might expect more heterogeneity due to country- and timing-specific differences in folate intake. Secondly, our results were largely null – confounding by folic acid supplementation, which is indirectly associated with alcohol consumption [14,68], is unlikely to be exaggerating estimates of the association between maternal alcohol and offspring methylation. We also consider that some of our findings may be affected by selection bias: women who are actively trying to get pregnant may abstain from drinking alcohol, but these women were excluded from our analyses of sustained and binge drinking.…”

“…Evidence of an effect of light-to-moderate levels of prenatal alcohol exposure is sparse and inconsistent. Although the majority of systematic reviews and studies published after these reviews have not found convincing evidence of association between light-to-moderate drinking and adverse offspring health and neurodevelopment [7–14], a recent comprehensive review of prospective studies found suggestive evidence of an association between mothers consuming up to four UK units of alcohol per week and babies born small-for-gestational age or preterm [15]. Furthermore, results from quasi-experimental study designs, which are more robust to the presence of confounding by parental socio-economic factors, have shown some evidence of effect of (mostly light-to-moderate) maternal alcohol consumption on offspring cognition and behaviour [16–18].…”