Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure

Prenatal alcohol exposure may be a risk factor for the development of alcohol problems in humans. We use data beginning with interviews of women in prenatal care at midpregnancy to predict alcohol use and alcohol-related problems in their offspring now aged 21 years. Maternal drinking during pregnancy was assessed from November 4, 1974, through October 2, 1975, along with measures of maternal smoking, use of caffeine and other drugs, and demographic factors. Family history of alcohol problems was assessed from interviews with parents when offspring were 14 years of age and updated when offspring were 21 years of age. Measures of parental use of alcohol and other drugs and many aspects of the family environment were assessed at 7 different ages, prenatally through 21 years. Young adult offspring (age, 21 years [N = 433]) provided self-reports of drinking quantity and frequency and completed the Alcohol Dependence Scale as a measure of alcohol-related problems and dependence. Univariate, partial least squares, and regression analyses indicate that prenatal alcohol exposure is significantly associated with alcohol problems at 21 years of age. The relationship persists independent of the effects of family history of alcohol problems, nicotine exposure, other prenatal exposures, and postnatal environmental factors including parental use of other drugs. Prenatal nicotine exposure was not associated with alcohol problems by offspring at 21 years of age. Prenatal alcohol exposure is a risk factor for the development of drinking problems in humans. Potential mechanisms for the role of fetal exposure and the development of alcohol problems deserve study.

Little is known about the contribution of fetal alcohol exposure to the development of alcohol disorders in early adulthood. To examine the independent effect of maternal alcohol use during early vs late periods in pregnancy on the time of onset of alcohol disorders in offspring. Follow-up study of the Mater-University of Queensland Study of Pregnancy and Its Outcomes (MUSP), a population-based birth cohort study commenced in Brisbane, Australia, in 1981 and designed to examine the association of maternal alcohol exposure with the onset of alcohol disorders. Mothers and children were followed up at birth, 6 months, and 5, 14, and 21 years after the initial interview. Maternal alcohol use was assessed before pregnancy, in early and late pregnancy, and at the 5- and 14-year follow-up visits. Alcohol disorders in early adulthood were assessed at age 21 years using the lifetime version of the Composite International Diagnostic Interview-computerized version. Population-based birth cohort study. A subsample of 2138 participants for whom complete data were available at the 21-year follow-up. Onset of alcohol disorder from adolescence to 21 years of age. In utero alcohol exposure of 3 or more glasses was associated with alcohol disorders. The fully adjusted odds ratios (95% confidence intervals) of developing early-onset alcohol disorders at age 21 years were 2.95 (1.62-5.36) for those exposed to maternal drinking in early pregnancy and 1.35 (0.69-2.63) for those exposed in late pregnancy. There was also a strong association between alcohol exposure in early pregnancy and late-onset alcohol disorders (odds ratio, 3.29 [95% confidence interval, 1.74-6.24]). Our results provide support for a biological origin of adult alcohol disorders and suggest that the association is not explained solely by maternal drinking or smoking during childhood and adolescence or other intervening factors. Further research is needed to understand the mechanisms underlying the association.

Developmental studies often assess the effect of treatment of the pregnant mother on offspring. The use of multiparous species such as rats and mice in such studies creates a special set of design and analysis problems. These arise for two reasons. First, the availability of many offspring per litter tempts the experimenter to inflate sample size by treating scores from several pups per litter as independent observations. Second, large litter size seldom makes it practical to measure exposure effects in all offspring of an exposed dam. Such studies commonly involve two-stage sampling: Drawing a random sample of dams for treatment, then drawing a second sample of pups per dam for neurobehavioral measurements. In this article, such sampling was modeled by two different simulations. The first, a standard Monte-Carlo approach, sampled from random-normal distributions for litter mean and within-litter variability. The second simulation sampled without replacement from actual data on weight of all pups in a series of 39 nontreated rat litters. These mutually-supportive approaches demonstrate that litter effects, even over as few as three litters, are generally large and statistically meaningful. Consequently, statistical significance tests are sensitive to litter effects. Inflation of sample size by treating as few as 2 pups per litter as independent measurements can almost triple the nominal 0.05 alpha level. Furthermore, two-stage sampling increases the within-treatment error term and correspondingly reduces statistical power relative to one-stage sampling.(ABSTRACT TRUNCATED AT 250 WORDS)