First-Trimester Maternal Alcohol Consumption and the Risk of Infant Oral Clefts in Norway: A Population-based Case-Control Study

Epidemiology Branch, National Institute of Environmental Health Sciences/National Institutes of Health, Durham, NC 27709, USA.
American journal of epidemiology (Impact Factor: 5.23). 10/2008; 168(6):638-46. DOI: 10.1093/aje/kwn186
Source: PubMed


Although alcohol is a recognized teratogen, evidence is limited on alcohol intake and oral cleft risk. The authors examined
the association between maternal alcohol consumption and oral clefts in a national, population-based case-control study of
infants born in 1996–2001 in Norway. Participants were 377 infants with cleft lip with or without cleft palate, 196 with cleft
palate only, and 763 controls. Mothers reported first-trimester alcohol consumption in self-administered questionnaires completed
within a few months after delivery. Logistic regression was used to calculate odds ratios and 95% confidence intervals, adjusting
for confounders. Compared with nondrinkers, women who reported binge-level drinking (≥5 drinks per sitting) were more likely
to have an infant with cleft lip with or without cleft palate (odds ratio = 2.2, 95% confidence interval: 1.1, 4.2) and cleft
palate only (odds ratio = 2.6, 95% confidence interval: 1.2, 5.6). Odds ratios were higher among women who binged on three
or more occasions: odds ratio = 3.2 for cleft lip with or without cleft palate (95% confidence interval: 1.0, 10.2) and odds
ratio = 3.0 for cleft palate only (95% confidence interval: 0.7, 13.0). Maternal binge-level drinking may increase the risk
of infant clefts.

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Available from: Lisa A. DeRoo
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    • "Secondhand smoke exposure does not seem to increase risk (43). Maternal alcohol consumption is controversial, although binge drinking may increase risk (44). Confounding between cigarette and alcohol use occurs frequently and their effects should be analyzed independently. "
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    ABSTRACT: Orofacial clefts comprise a range of congenital deformities and are the most common head and neck congenital malformation. Clefting has significant psychological and socio- economic effects on patient quality of life and require a multidisciplinary team approach for management. The complex interplay between genetic and environmental factors play a significant role in the incidence and cause of clefting. In this review, the embryology, classification, epidemiology, and etiology of cleft lip are discussed. The primary goals of surgical repair are to restore normal function, speech development, and facial esthetics. Different techniques are employed based on surgeon expertise and the unique patient presentations. Pre-surgical orthopedics are frequently employed prior to definitive repair to improve outcomes. Long term follow up and quality of life studies are discussed.
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    • "Reporting any binge drinking ( 5 drinks) during the first trimester has been associated with increased risk of oral clefts (DeRoo et al., 2008), and consumption of only 2 to 3.5 drinks per week during the first trimester has been associated with an increased chance of fetal death (Andersen et al., 2012). The animal studies, with their possibility of using an experimental design, have contributed considerably within this field of research. "
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    ABSTRACT: Fetal binge alcohol exposure has been associated with neurobehavioral and cognitive symptoms. This study explored whether binge drinking mainly before recognition of pregnancy predicted high symptom scores on the Strengths and Difficulties Questionnaire (SDQ) in 5.5-year-old children. In a population-based, longitudinal study representative of pregnant women in Oslo, Norway, questionnaires were answered at 17 and 30 weeks of pregnancy, 6 months after term, and at child age 5.5 years (n = 1,116, constituting 66% of the original cohort). Logistic regression analyses identified factors predicting high SDQ scores, and multiple regression analyses identified direct effects on the SDQ Total. Binge exposure (≥5 standard units per occasion [SUpo]) during pregnancy week 0 to 6, that is, 0 to 4 weeks after conception, predicted scores in the Abnormal and Borderline range on the SDQ in 5.5-year-olds, after adjusting for other confounding variables. Very early binge exposure less often than once a week predicted high symptom scores on the SDQ Total (p = 0.05) and Hyperactivity/Inattention (significant), while exposure at least once a week demonstrated a 3- to 5-fold significant increase in high symptom scores on Total, Emotional, and Conduct problems. Reporting ≥8 SUpo had stronger predictive power than reporting 5 to 7 SUpo. The results were not explained by participants reporting major lifetime depression. Other predictive factors, although weaker, were maternal symptoms of depression and anxiety during the child's infancy. High education (mother and father), high income (maternal partner), higher child birth weight, and child female sex reduced the likelihood of high SDQ symptom scores. Path analysis demonstrated early binge exposure to have a direct effect on the SDQ Total score. Binge drinking up to 4 weeks after conception had a strong and direct predictive effect on SDQ symptom scores in 5.5-year-olds. These results strongly support the advice to avoid binge drinking when planning pregnancy.
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    • "Previous research has reported a positive association between occurrence of NSCL/P and oxidative stress-initiating environmental factors [59]. Oxidative generation of DSBs and other types of DNA lesions have been reported to arise from many cleft-related environmental factors, such as maternal exposure to alcohol, nicotine, phenytoin, and valproic acid [59], [60], [61], [62], [63], [64], [65], [66], [67]. Among these, valproic acid has been reported to down-regulate homologous recombination DNA repair genes (e.g. "
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