Objectives: Fetal alcohol spectrum disorders are more common in disadvantaged populations. Environmental factors, like suboptimal nutrition, may potentiate the developmental effects of prenatal alcohol exposure. To evaluate the impact of micronutrients, including choline, on reduction of effects of exposure, we examined timing and dose of alcohol and effects of nutritional supplementation at two OMNI-Net sites in Western Ukraine that included high and low risk individuals. Methods: Alcohol-using and nondrinking women were randomized to one of three multivitamin/mineral supplement groups: none, multivitamins/minerals (MVM), and multivitamin/minerals plus choline. Children (N = 367) were tested at 6 months with the Bayley Scales of Infant Development (2nd ED) yielding standard scores for Mental Development Index (MDI), Psychomotor Development Index (PDI) and Behavior. Results: Generalized linear modeling was used: (1) for factorial analysis of effects of alcohol group, multivitamin/minerals, and choline supplementation; and (2) to examine the relationship between amount and timing of alcohol (ounces of absolute alcohol/day [ozAA/day] peri-conception and on average in the second trimester) and MVM supplementation on developmental outcomes while controlling sex, social class, and smoking. MDI was significantly impacted by peri-conceptual alcohol dose ($$\upchi_{(1)}^{2} = 8.54$$χ(1)2=8.54, p < .001) with more alcohol associated with lower scores and males more negatively affected than females ($$\upchi_{(3)}^{2} = 11.04$$χ(3)2=11.04, p < .002). Micronutrient supplementation had a protective effect; those receiving supplements performed better ($$\upchi_{(1)}^{2} = 8.03$$χ(1)2=8.03, p < .005). The PDI motor scores did not differ by group but were affected by peri-conceptual alcohol dose ($$\upchi_{(1)}^{2} = 4.17$$χ(1)2=4.17, p < .04). Conclusions for Practice: Multivitamin/mineral supplementation can reduce the negative impact of alcohol use during pregnancy on specific developmental outcomes.

Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a “pathway to pathology”. In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-ɣ IL-10, TNF-β TNF-α and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.

The 2012 meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) focused on the development and ethics of biomarkers for fetal alcohol exposure. This one-day international conference brought students and trainees together with clinicians and researchers to discuss the latest research on FASD. One keynote speaker discussed the value of profiling epigenetic modifications in readily available fetal tissues to diagnose fetal exposure to environmental agents, while the second speaker discussed the ethics of biomarker development within the context of core principles of justice, autonomy, beneficence and non-maleficence. Three sessions of short data talks informed the audience of research advances with particular emphasis on the diagnosis of FASD. Other activities included updates on FASD-related activities by representatives of government agencies, a report on the implementation FASD-related diagnostic criteria in the fifth edition of the Diagnostic and Statistical Manual (DSM-5) of the American Psychiatric Association and a networking lunch, and the presentation of the "Merit Award" to Dr. Nathan Muraski for his work on behavioral outcomes of fetal alcohol exposure. The capstone of the meeting was the presentation of the "Henri Rosett" award to Dr. Denis Viljoen, in recognition of his role in raising awareness about the incidence of FASD in South Africa and in promoting FASD prevention and treatment programs as chairperson and chief executive officer of the Foundation for Alcohol Related Research (FARR).

Background: Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods: Subjects were 407 youth with prenatal alcohol exposure (n = 192) and controls (n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years] ) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. Results: No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Conclusions: Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains.