A pilot study of alcohol exposure and pharmacokinetics in women with or without children with fetal alcohol syndrome

Foundation for Alcohol Related Research, University of Cape Town Medical School, Cape Town, South Africa.
Alcohol and Alcoholism (Impact Factor: 2.89). 11/2004; 39(6):503-8. DOI: 10.1093/alcalc/agh089
Source: PubMed


To determine the alcohol exposure and pharmacokinetics of alcohol in a group of women who had given birth to children with FAS, compared with women who had not given birth to FAS children.
10 women who had given birth to FAS children (FAS mothers) and 20 Controls were studied to determine how they metabolize alcohol in a single limited-access quasi-experimental session of voluntary consumption of alcohol. They had free choice in the consumption of any amount of their favourite beverage for approximately 2.5 h, but their drinking was terminated if the breath alcohol concentrations (BrAC) exceeded 150 mg%. BrACs was measured during ethanol consumption and for several hours after, for estimation of alcohol exposure and pharmacokinetics.
FAS mothers consumed significantly larger amounts of alcohol, and achieved significantly higher peak BrAC levels than Controls. The rate of decline of alcohol from the circulation (beta-60) showed a 2-fold variation across subjects but there was no significant difference between the two groups.
This study did not show any difference in alcohol pharmacokinetics in free-choice drinking by non-pregnant women, who either have given or have never given birth to FAS children. However, mothers of FAS children tend to consume more alcohol per session. Future studies in larger samples will be needed to confirm these findings and to examine drinking patterns and other factors that may increase the risk of FAS in children of women who drink alcohol during pregnancy.

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    • "It is interesting, however, that the drinking data used in the regression model explain 60 to 65% of the variance in diagnosis, which is similar to the variance in child outcomes explained in complex structural equation models of child dysmorphology and neurobehavior (62 to 55%) that incorporate multiple measures of risk: socioeconomic status, childbearing history, and maternal physical variables (May et al., 2011, 2013b). Furthermore, genetic (Khaole et al., 2004) and epigenetic variables also influence outcome. They are also beyond the scope of these epidemiologic sample data and of this paper. "
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    ABSTRACT: Concise, accurate measures of maternal prenatal alcohol use are needed to better understand fetal alcohol spectrum disorders (FASD). Measures of drinking by mothers of children with specific FASD diagnoses and mothers of randomly-selected controls are compared and also correlated with physical and cognitive/behavioral outcomes. Measures of maternal alcohol use can differentiate maternal drinking associated with FASD from that of controls and some from mothers of alcohol-exposed normals. Six variables that combine quantity and frequency concepts distinguish mothers of FASD children from normal controls. Alcohol use variables, when applied to each trimester and three months prior to pregnancy, provide insight on critical timing of exposure as well. Measures of drinking, especially bingeing, correlate significantly with increased child dysmorphology and negative cognitive/behavioral outcomes in children, especially low non-verbal IQ, poor attention, and behavioral problems. Logistic regression links (p<.001) first trimester drinking (vs. no drinking) with FASD, elevating FASD likelihood 12 times; first and second trimester drinking increases FASD outcomes 61 times; and drinking in all trimesters 65 times. Conversely, a similar regression (p=.008) indicates that drinking only in the first trimester makes the birth of a child with an FASD 5 times less likely than drinking in all trimesters. There is significant variation in alcohol consumption both within and between diagnostic groupings of mothers bearing children diagnosed within the FASD continuum. Drinking measures are empirically identified and correlated with specific child outcomes. Alcohol use, especially heavy use, should be avoided throughout pregnancy.
    Drug and alcohol dependence 08/2013; 133(2). DOI:10.1016/j.drugalcdep.2013.07.013 · 3.42 Impact Factor
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    • "Larger women appear to be less likely to give birth to a child with an FASD (Khaole et al., 2004; May et al, 2004); 2005, 2008). This may be both a physiological effect and evidence of poor nutrition as enhancing risk for an FASD (Khaole et al., 2004; Sokol, et al., 1986; Abel and Hannigan, et al, 2005; Abel, 1998; Badger et al., 2005; Shankar et al., 2006, 2007; Thomas et al., 2004). "
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    ABSTRACT: Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R² = .30, p < .001), followed by maternal demographics (R² = .24, p < .001), maternal physical characteristics (R²=.15, p < .001), and childbearing variables (R² = .06, p < .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β = 0.61, p < .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables.
    Drug and alcohol dependence 06/2011; 119(1-2):18-27. DOI:10.1016/j.drugalcdep.2011.05.009 · 3.42 Impact Factor
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    • "Also significant are the mother's physical characteristics . For example, in both Italy and South Africa it has been documented that smaller mothers are more likely to bear a child with an FASD, presumably due to higher blood alcohol concentrations produced in the mother and therefore reaching the fetus [Khaole et al., 2004], Also significant in such models are the mother's social status and living conditions (e.g., low SES) which are highly influential on both drinking pattern [May et al., 2008] and in fetal outcome [Bingol et al., 1987]. "
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    ABSTRACT: Researching the epidemiology and estimating the prevalence of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) for mainstream populations anywhere in the world has presented a challenge to researchers. Three major approaches have been used in the past: surveillance and record review systems, clinic-based studies, and active case ascertainment methods. The literature on each of these methods is reviewed citing the strengths, weaknesses, prevalence results, and other practical considerations for each method. Previous conclusions about the prevalence of FAS and total FASD in the United States (US) population are summarized. Active approaches which provide clinical outreach, recruitment, and diagnostic services in specific populations have been demonstrated to produce the highest prevalence estimates. We then describe and review studies utilizing in-school screening and diagnosis, a special type of active case ascertainment. Selected results from a number of in-school studies in South Africa, Italy, and the US are highlighted. The particular focus of the review is on the nature of the data produced from in-school methods and the specific prevalence rates of FAS and total FASD which have emanated from them. We conclude that FAS and other FASD are more prevalent in school populations, and therefore the general population, than previously estimated. We believe that the prevalence of FAS in typical, mixed-racial, and mixed-socioeconomic populations of the US is at least 2 to 7 per 1,000. Regarding all levels of FASD, we estimate that the current prevalence of FASD in populations of younger school children may be as high as 2-5% in the US and some Western European countries.
    Developmental Disabilities Research Reviews 01/2009; 15(3):176-92. DOI:10.1002/ddrr.68 · 2.75 Impact Factor
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Nathaniel C O Khaole