Clinical Features of Typically Developing Children With and Without Prenatal Alcohol Exposure.

OBJECTIVE: To determine if prenatal alcohol exposure (PAE) affected physical and cognitive/behavioral outcomes in apparently typically developing, first-grade children. STUDY DESIGN: Three groups were compared: children with fetal alcohol spectrum disorders (FASD); children with PAE without FASD; and children without PAE. RESULTS: The three groups were significantly different on most physical traits and fewer neurodevelopmental traits. Two-group comparisons of exposed and unexposed, non-FASD groups were statistically different on: height, weight, head circumference (OFC), body mass index (BMI), and palpebral fissure length (PFL). Neurobehavioral outcomes were significant in three-group, but not two-group, comparisons. Few sex differences were observed; however, sex ratios indicated fewer male offspring in first grade among women who consumed 6+ drinks per occasion during pregnancy. For weight, OFC, BMI, age, rural residence, and drinking measures, mothers of exposed children without FASD were intermediaries between, and significantly different from, the other maternal groups. Adjusted for socioeconomic covariates, multivariate analysis of covariance (MANCOVA), three-group comparisons were significantly different for cognitive/behavioral variables (p<.001); however, two-group neurobehavior comparisons for children without FASD were not significant (p>.05). Physical trait MANCOVA comparisons of the non-FASD groups were significant only for weight (p<.004) when tested univariately and through stepdown analysis. Socioeconomic-adjusted trend plots were in the expected direction for nonverbal IQ, problem behaviors, attention, height, weight, OFC, vermilion, PFL, and total dysmorphology score. CONCLUSIONS: Even when meeting developmental norms, children with PAE exhibited trends of poorer growth and cognitive/behavioral traits than children without PAE. These findings support the notion that abstinence during pregnancy is best.

Contribution of ferritin and zinc to adverse infant outcomes among pregnancies with prenatal alcohol exposure in South Africa.

Nutritional status during pregnancy can impact fetal development, yet less is known about how alcohol may interact with nutritional status to influence infant outcomes. Pregnant women (n=196) completed 2, 24-hour dietary recalls and provided a venous blood sample to be analyzed for liver enzymes (GGT -gamma-glutamyl transferase; ALT -alanine transaminase; and AST -aspartate transferase), iron, ferritin, and zinc concentrations. Infants were assessed at 6 weeks of age. Women who consumed alcohol had significantly higher ferritin levels compared to non-drinkers (51.8 vs. 34.2). While 44% of women had ferritin <30 ug/L (an indicator of iron deficiency), and 24% of women were low in serum iron, and 72% were low in serum zinc. All six drinking measures for 1st trimester and previous week were significantly correlated with GGT and AST levels while 4 out of 6 alcohol measures were associated with levels of ALT and ferritin. At six weeks of age, nearly all physical measures differentiated infants with alcohol exposure from infants without exposure. Controlling for six covariates, maternal ferritin was significantly and inversely associated with infant head circumference (OFC) centile among infants with alcohol exposure. GGT was inversely associated with infant height and weight centile among unexposed infants. Seventy-four percent (74%) of mothers who consumed alcohol were found to be low in serum zinc, yet higher maternal zinc was associated with more dysmorphology. This may indicate that higher zinc status is not protecting the fetus from the teratogenic effects of alcohol. Prenatal alcohol exposure, ferritin, and zinc status influence infant growth and neurodevelopment.

Maternal risk factors for fetal alcohol spectrum disorders: Distal variables.

BACKGROUND: A variety of maternal risk factors for fetal alcohol spectrum disorders (FASD) have been described in the literature. Here, we conducted a multivariate analysis of a large array of potential distal influences on FASD risk. METHODS: Interviews were conducted with 2515 mothers of first-grade students whose children were evaluated to assess risk for FASD. Topics included: physical/medical status, childbearing history, demographics, mental health, domestic violence, and trauma. Regression modeling utilized usual level of alcohol consumption by trimester and six selected distal variables (maternal head circumference, body mass index, age at pregnancy, gravidity, marital status, and formal years of education) to differentiate children with FASD from control children. RESULTS: Despite individual variation in distal maternal risk factors among and within the mothers of children with each of the common diagnoses of FASD, patterns emerged that differentiated risk among mothers of children with FASD from mothers whose children were developing typically. Case-control comparisons indicate that mothers of children with FASD were significantly smaller physically, had higher gravidity and parity, and experienced more miscarriages and stillbirths, were less likely to be married, reported later pregnancy recognition, more depression, and lower formal educational achievement. They were also less engaged with a formal religion, were less happy, suffered more childhood trauma and interpersonal violence, were more likely to drink alone or with her partner, and drank to deal with anxiety, tension, and to be part of a group. Regression analysis showed that the predictor variables explain 57.5% of the variance in fetal alcohol syndrome (FAS) diagnoses, 30.1% of partial FAS (PFAS) diagnoses, and 46.4% of alcohol-related neurodevelopmental disorder (ARND) diagnoses in children with FASD compared to controls. While the proximal variables explained most of the diagnostic variance, six distal variables explained 16.7% (1 /6 ) of the variance in FAS diagnoses, 13.9% (1 /7 ) of PFAS, and 12.1% (1 /8 ) of ARND. CONCLUSIONS: Differences in distal FASD risks were identified. Complex models to quantify risk for FASD hold promise for guiding prevention/intervention.

Maternal dietary intake among alcohol-exposed pregnancies is linked to early infant physical outcomes in South Africa.

Maternal dietary intake is likely a contributing factor to fetal alcohol spectrum disorders (FASD). Two, 24-hour dietary recalls were completed by pregnant women (n = 196) in South African communities with high rates of FASD. More than 50% of all women in this study were below the Estimated Average Requirement (EAR) for pregnancy for vitamins A, C, D, E, riboflavin, vitamin B6, folate, calcium, magnesium, iron, and zinc. More than 90% of mothers were below the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for pregnancy on vitamin A, K, D, E, choline, calcium, magnesium, zinc, and potassium. More than 80% were below RDA/AI for pantothenic acid, vitamin B6, and folate. Women who consumed alcohol reported significantly lower intake of calcium and three saturated fatty acids and significantly higher intake of two monounsaturated fatty acids. On average, infants were < 40th centile on length, weight, and head circumference at 6 weeks old, regardless of alcohol exposure. Twenty nutrients correlated with at least one measure of 1st trimester drinking (drinks per drinking day, number of drinking days per week, and/or total drinks per week). Nutrients included four saturated fatty acids, eight amino acids, calcium, B-complex vitamins, choline, and betaine. Calcium correlated with all three drinking measures. Further analyses revealed seven nutrients were associated with infant length, weight, and/or head circumference among unexposed infants, and 12 nutrients were associated among infants with prenatal alcohol exposure. Inadequate maternal dietary intake, with alcohol exposure, may increase risk for poor infant growth and likelihood of FASD in this population.

Assessing the sensitivity and specificity of phosphatidylethanol (PEth) cutoffs to identify alcohol exposed pregnancies.

In the literature on alcohol use biomarkers, there has been debate as to what a valid and/or utilitarian cut off level should be for various research applications. In this manuscript, we assessed the sensitivity and specificity of multiple cutoff values for phosphatidylethanol (PEth) from bloodspots relative to self-report, the Alcohol Use Disorder Identification Test (AUDIT) scores, and another alcohol use biomarker ethyl glucuronide (EtG) from fingernails in a sample of 222 pregnant women in the Western Cape Province of South Africa. Receiver operating characteristic (ROC) curves were used to assess the area under the curve (AUC) and assess PEth cutoff values of ≥2, ≥4, ≥8, ≥14, and ≥20 nanograms per milliliter (ng/ml). The highest AUC value was attained when PEth was compared to an AUDIT score of 1 or more. Depending on the cutoff used to determine alcohol consumption, PEth identified 47%-70% of the individuals as alcohol-consuming while 62.6%-75.2% were identified by self-reported measures, and 35.6% were identified by EtG. In this sample, sensitivity and accuracy were highest at less stringent PEth cutoffs when compared to self-report, AUDIT score of 1 or more, 5 or more, 8 or more, and EtG ≥ 8 picograms per milligram (pg/mg). For research purposes, less stringent cutoffs, such as PEth ≥ 8 ng/ml, may be considered a valid, positive cutoff for identifying women who consume alcohol during pregnancy in this population. A cutoff of PEth ≥ 20 ng/ml may miss individuals who reported consuming alcohol (false negatives).

Relationship-based intervention for children who were prenatally alcohol exposed in South Africa.

BACKGROUND: This early intervention study investigated the effectiveness of a relationship-based, developmental enhancement process for children who were prenatally exposed to alcohol in the South African context. METHODS: Groups were created according to the child's level of risk for alcohol-related developmental issues based on each mother's alcohol use during pregnancy as assessed using the Alcohol Use Disorders Identification Test (AUDIT). Primary caregiver/child dyads were the focus of the intervention and child development was monitored by the Ages and Stages Questionnaire (ASQ). Eighteen caregiver/child dyads were in the heavily alcohol-exposed group, and 20 caregiver/child dyads were in the no or light alcohol-exposure group. The Home Observation Measurement of the Environment (HOME) was measured pre and post intervention. RESULTS: The results indicated significant improvements in the home environment (p < .001) post-intervention for the entire cohort. For the total HOME score, there was a statistically significant main effect for time (pre- vs post-test), F(1, 36)= 65.205, p < .001, partial η2 = .64. with 99% confidence limits from .35 to .78. The offspring and parents from both the heavy alcohol exposure group and the no/low alcohol exposure group benefitted from the intervention over the duration of the intervention. Of the HOME domains affected, responsivity was the most improved in the households. The children's scores on the ASQ varied substantially over the months of the intervention, and the offspring of the heavy exposure group often performed significantly worse than the no/low exposure group. Nevertheless, further analysis revealed that children with the lowest performance at baseline improved their performance on most ASQ domains throughout the intervention and performed significantly better on all ASQ domains over time and at completion of the intervention. CONCLUSIONS: This relationship-based, early intervention program for children resulted in benefits to all of the children over time.

Multifaceted case management during pregnancy is associated with better child outcomes and less fetal alcohol syndrome.

BACKGROUND: Pregnant women participated in multifaceted case management (MCM) to prevent Fetal Alcohol Spectrum Disorders (FASD). METHODS: Women recruited from antenatal clinics for a longitudinal child development study were screened for alcohol use. Forty-four pregnant women were defined as high-risk drinkers on the Alcohol Use Disorder Identification Test (AUDIT) by an AUDIT score ≥8 and participated in 18 months of MCM to facilitate reduction or cessation of alcohol consumption. Forty-one women completed MCM. Fifty-five equally high-risk women who received standard antenatal care comprised the comparison/control group. Development in offspring was evaluated by a blinded interdisciplinary team of examiners through 5 years of age. RESULTS: At five years of age, more children (34%) of MCM participating women did not meet the criteria for FASD vs. non-MCM offspring (22%). Furthermore, a statistically significant (p = .01) lower proportion of MCM offspring (24%) was diagnosed with fetal alcohol syndrome (FAS) compared to controls (49%). Children of MCM participants had significantly (p < .05) better physical outcomes: lower total dysmorphology scores, larger head circumferences, longer palpebral fissures, and higher midfacial measurements. Neurodevelopment results showed mixed outcomes. While Bayley developmental scores indicated that MCM offspring were performing significantly worse on most domains through 18 months, group scores equalized and were not significantly different on Kaufman Assessment Battery neurobehavioral measures by five years. Regression analyses indicated that offspring of women who received standard antenatal care were associated with significantly more negative outcomes than MCM offspring: a diagnosis of FAS (OR = 3.2; 95% CI: 1.093-9.081), microcephaly (OR = 5.3; 95% CI: 2.1-13.5), head circumference ≤10th centile (OR = 4.3; 95%CI: 1.8-10.4), and short palpebral fissures (OR = 2.5; 95% CI: 1.0-5.8). CONCLUSION: At age five, proportionally fewer children of MCM participants qualified for a diagnosis of FAS, and proportionally more had physical outcomes indicating better prenatal brain development. Neurobehavioral indicators were not significantly different from controls by age five.KEY MESSAGESMultifaceted Case Management (MCM) was designed and employed for 18 months during the prenatal and immediate postpartum period to successfully meet multiple needs of women who had proven to be very high risk for birthing children with fetal alcohol spectrum disorders (FASD).Offspring of the women who participated in MCM were followed up through age five years and were found to have significantly better physical outcomes on multiple variables associated with fetal alcohol syndrome (FAS) and FASD, such as larger head circumferences and fewer minor anomalies, than those children born to equally at-risk women not receiving MCM.Fewer children of women receiving MCM were diagnosed with FASD than the offspring of equally-at-risk controls, and significantly (p = .01) fewer MCM offspring had FAS, the most severe FASD diagnosis.

Maternal and paternal risk factors for fetal alcohol spectrum disorders: Alcohol and other drug use as proximal influences.

OBJECTIVE: To explore and analyze the significance of proximal influences of maternal and paternal traits associated with bearing a child with a fetal alcohol spectrum disorder (FASD). METHODS: Aggregated, maternal interview-collected data (N = 2515) concerning alcohol, tobacco, and other drug use were examined to determine risk for FASD from seven cross-sectional samples of mothers of first-grade students who were evaluated for a possible diagnosis of FASD. RESULTS: Mothers of children with fetal alcohol syndrome (FAS) reported the highest alcohol use throughout pregnancy, proportion of binge drinking, drinks per drinking day (DDD), drinking days per week, and total drinks per week. Mothers of children with FAS also consumed significantly more alcohol than mothers of children with partial FAS (PFAS), alcohol-related neurodevelopmental disorder (ARND), or typically developing controls. Mothers of children with PFAS and ARND reported similar drinking patterns, which exposed fetuses to 3-4 times more alcohol than mothers of controls, but the PFAS group was more likely than the ARND group to abstain in latter trimesters. Fathers of all children were predominantly drinkers (70%-85%), but more fathers of children with FASD binged heavily on more days than fathers of controls. Compared to the few mothers of controls who used alcohol during pregnancy, the ARND group binge drank more (3+ DDD) throughout pregnancy and drank more DDD before pregnancy and first trimester. Regression analysis, controlling for tobacco use, indicated that mothers who reported drinking <1 DDD were significantly more likely than abstainers to bear a child with FASD (OR = 2.75) as were those reporting higher levels such as 5-5.9 DDD (OR = 32.99). Exclusive, first-trimester maternal drinking increased risk for FASD five times over that of abstinence (p < 0.001, OR = 5.05, 95% CI: 3.88-6.58), first- and second-trimester drinking by 12.4 times, and drinking all trimesters by 16 times (p < 0.001, OR = 15.69, 95% CI: 11.92-20.64). Paternal drinking during and prior to pregnancy, without adjustment, increased the likelihood of FASD significantly (OR = 1.06 and 1.11, respectively), but the significance of both relationships disappeared when maternal alcohol and tobacco use were controlled. CONCLUSIONS: Differences in FASD risk emerged from the examination of multiple proximal variables of maternal alcohol and tobacco use, reflecting increased FASD risk at greater levels of maternal alcohol consumption.

Untargeted Metabolome Analysis of Alcohol-Exposed Pregnancies Reveals Metabolite Differences That Are Associated with Infant Birth Outcomes.

Prenatal alcohol exposure can produce offspring growth deficits and is a leading cause of neurodevelopmental disability. We used untargeted metabolomics to generate mechanistic insight into how alcohol impairs fetal development. In the Western Cape Province of South Africa, 52 women between gestational weeks 5-36 (mean 18.5 ± 6.5) were recruited, and they provided a finger-prick fasting bloodspot that underwent mass spectrometry. Metabolomic data were analyzed using partial least squares-discriminant analyses (PLS-DA) to identify metabolites that correlated with alcohol exposure and infant birth outcomes. Women who consumed alcohol in the past seven days were distinguished by a metabolite profile that included reduced sphingomyelins, cholesterol, and pregnenolones, and elevated fatty acids, acyl and amino acyl carnitines, and androsterones. Using PLS-DA, 25 of the top 30 metabolites differentiating maternal groups were reduced by alcohol with medium-chain free fatty acids and oxidized sugar derivatives having the greatest influence. A separate ortho-PLS-DA analysis identified a common set of 13 metabolites that were associated with infant length, weight, and head circumference. These included monoacylglycerols, glycerol-3-phosphate, and unidentified metabolites, and most of their associations were negative, implying they represent processes having adverse consequences for fetal development.

The prevalence of fetal alcohol spectrum disorders in rural communities in South Africa: A third regional sample of child characteristics and maternal risk factors.

BACKGROUND: This study is the ninth cross-sectional community study of fetal alcohol spectrum disorders (FASD) conducted by the multidisciplinary Fetal Alcohol Syndrome Epidemiology Research team in the Western Cape Province of South Africa. It is the third comprehensive study of FASD in a rural, agricultural region of South Africa. METHODS: Population-based, active case ascertainment methods were employed among a school-based cohort to assess child physical and neurobehavioral traits, and maternal risk factor interviews were conducted to identify all children with FASD to determine its prevalence. RESULTS: Consent was obtained for 76.7% of 1158 children attending first grade in the region's public schools. Case-control results are presented for 95 with fetal alcohol syndrome (FAS), 64 with partial fetal alcohol syndrome (PFAS), 77 with alcohol-related neurodevelopmental disorder (ARND), 2 with alcohol-related birth defects (ARBD), and 213 randomly-selected controls. Four techniques estimating FASD prevalence from in-person examinations and testing yielded a range of total FASD prevalence of 206-366 per 1000. The final weighted, estimated prevalence of FAS was 104.5 per 1000, PFAS was 77.7 per 1000, ARND was 125.2 per 1000, and total FASD prevalence was 310 per 1000 (95% CI = 283.4-336.7). Expressed as a percentage, 31% had FASD. Although the rate of total FASD remained steady over 9 years, the proportion of children within the FASD group has changed significantly: FAS trended down and ARND trended up. A detailed evaluation is presented of the specific child physical and neurobehavioral traits integral to assessing the full continuum of FASD. The diagnosis of a child with FASD was significantly associated with maternal proximal risk factors such as: co-morbid prenatal use of alcohol and tobacco (OR = 19.1); maternal drinking of two (OR = 5.9), three (OR = 5.9), four (OR = 38.3), or more alcoholic drinks per drinking day; and drinking in the first trimester (OR = 8.4), first and second trimesters (OR = 17.7), or throughout pregnancy (OR = 18.6). Distal maternal risk factors included the following: slight or small physical status (height, weight, and head circumference), lower BMI, less formal education, late recognition of pregnancy, and higher gravidity, parity, and older age during the index pregnancy. CONCLUSION: The prevalence of FASD remained a significant problem in this region, but the severity of physical traits and anomalies within the continuum of FASD is trending downwards.

The influence of maternal weight and alcohol exposure on infant physical characteristics and neurodevelopmental outcomes.

Background: Mothers of children with fetal alcohol spectrum disorders tend to have lower weight compared to other mothers. Yet how alcohol and maternal weight may predispose infants to poorer physical growth and neurodevelopmental trajectories is relatively unexplained. Methods: South African mothers (n = 406) were recruited prenatally and their offspring were provided standardized dysmorphology and neurodevelopment examinations at 6 weeks and 9 months of age. Maternal weight was obtained postpartum, and linear mixed modeling determined whether postpartum maternal weight and prenatal alcohol exposure significantly influenced infant growth, dysmorphology, and neurodevelopment within the first year of life. Results: Postpartum maternal weight was positively associated with birth length, weight, and head circumference centile, but the rate of growth from birth to nine months was similar among all infants. Maternal weight was inversely associated with dysmorphology. Many infants in this population were performing within the borderline or extremely low range. Higher maternal weight was associated with significantly better cognitive and motor performance at 6 weeks; however, the rate of developmental growth was similar among all infants, regardless of postpartum maternal weight. Conclusion: Higher postpartum maternal weight may be a protective factor but does not eliminate the adverse effects of alcohol on infant growth and dysmorphology. Regardless of maternal weight, alcohol remains a powerful teratogen and moderate to high use prenatally can result in adverse infant physical and neurocognitive development.

The prevalence, child characteristics, and maternal risk factors for the continuum of fetal alcohol spectrum disorders: A sixth population-based study in the same South African community.

BACKGROUND: Prevalence and characteristics of fetal alcohol spectrum disorders (FASD) have been described previously in this community. METHODS: Active case ascertainment methods were employed in a new cross-sectional study with Revised Institute of Medicine criteria among first grade students (n = 735) via dysmorphology examinations and neurobehavioral assessments. Their mothers were interviewed regarding risk factors. Final diagnoses were assigned via structured case conferences. RESULTS: Children with fetal alcohol syndrome (FAS), partial FAS (PFAS), and alcohol related-neurodevelopmental disorder (ARND) were significantly different from controls on all cardinal variables, multiple dysmorphology traits and neurobehavioral performance. Mothers of children with FASD reported significantly more drinking before and during pregnancy (mothers of children with FAS reported 7.8 (±6.1) drinks per drinking day (DDD) prior to pregnancy and 5.1 (±5.9) after pregnancy recognition). Distal risk variables for a diagnosis on the continuum of FASD were: lower maternal height, weight, and body mass index; higher gravidity; lower education and household income; and later pregnancy recognition. Alcohol and tobacco remain the only commonly used drugs. Women reporting first trimester drinking of two DDD were 13 times more likely (95 % CI:1.3-133.4) to have a child with FASD than non-drinkers; and those who reported drinking throughout pregnancy were 19.4 times more likely (95 % CI:8.2-46.0) to have a child with FASD. CONCLUSION: Seventeen years after the first study in this community, FASD prevalence remains high at 16 %-31 %. The FAS rate may have declined somewhat, but rates of PFAS and ARND seemed to plateau, at a high rate.

Early-Life Predictors of Fetal Alcohol Spectrum Disorders.

BACKGROUND AND OBJECTIVES: Fetal alcohol spectrum disorders (FASD) comprise the continuum of disabilities associated with prenatal alcohol exposure. Although infancy remains the most effective time for initiation of intervention services, current diagnostic schemes demonstrate the greatest confidence, accuracy, and reliability in school-aged children. Our aims for the current study were to identify growth, dysmorphology, and neurodevelopmental features in infants that were most predictive of FASD at age 5, thereby improving the timeliness of diagnoses. METHODS: A cohort of pregnant South African women attending primary health care clinics or giving birth in provincial hospitals was enrolled in the project. Children were followed longitudinally from birth to 60 months to determine their physical and developmental trajectories (N = 155). Standardized protocols were used to assess growth, dysmorphology, and development at 6 weeks and at 9, 18, 42, and 60 months. A structured maternal interview, including estimation of prenatal alcohol intake, was administered at 42 or 60 months. RESULTS: Growth restriction and total dysmorphology scores differentiated among children with and without FASD as early as 9 months (area under the receiver operating characteristic curve = 0.777; P < .001; 95% confidence interval: 0.705-0.849), although children who were severely affected could be identified earlier. Assessment of developmental milestones revealed significant developmental differences emerging among children with and without FASD between 18 and 42 months. Mothers of children with FASD were significantly smaller, with lower BMIs and higher alcohol intake during pregnancy, than mothers of children without FASD. CONCLUSIONS: Assessment of a combination of growth, dysmorphology, and neurobehavioral characteristics allows for accurate identification of most children with FASD as early as 9 to 18 months.

A utilitarian comparison of two alcohol use biomarkers with self-reported drinking history collected in antenatal clinics.

BACKGROUND: Alcohol use is reported accurately among pregnant women in some populations. METHODS: Self-reported alcohol use via the AUDIT and 90-day recall for 193 women from antenatal clinics was compared to biomarker results: phosphatidylethanol (PEth) from bloodspots and ethyl glucuronide (EtG) in fingernails. RESULTS: AUDIT was positive for 67.9% of respondents, and 65.3% directly reported drinking. Individual biomarkers detected less drinking (PEth = 57.0%, EtG = 38.9%) than self-report. But 64.8% had drinking-positive values (>8 ng) on one or both biomarkers, which was not significantly different from self-report. Biomarkers indicated that 3.1% -6.8% of drinkers denied drinking. Combined biomarker sensitivity was 95% -80% and specificity 49% -76% for drinking in the previous 7-90 days. Combined biomarker results have their best yield (89.6%) and accuracy (78.8%) when measuring 90 day drinking. CONCLUSIONS: Women reported their alcohol use accurately, and the combined use of PEth and EtG is supported.

Who is most affected by prenatal alcohol exposure: Boys or girls?

OBJECTIVE: To examine outcomes among boys and girls that are associated with prenatal alcohol exposure. METHODS: Boys and girls with fetal alcohol spectrum disorders (FASD) and randomly-selected controls were compared on a variety of physical and neurobehavioral traits. RESULTS: Sex ratios indicated that heavy maternal binge drinking may have significantly diminished viability to birth and survival of boys postpartum more than girls by age seven. Case control comparisons of a variety of physical and neurobehavioral traits at age seven indicate that both sexes were affected similarly for a majority of variables. However, alcohol-exposed girls had significantly more dysmorphology overall than boys and performed significantly worse on non-verbal IQ tests than males. A three-step sequential regression analysis, controlling for multiple covariates, further indicated that dysmorphology among girls was significantly more associated with five maternal drinking variables and three distal maternal risk factors. However, the overall model, which included five associated neurobehavioral measures at step three, was not significant (p=0.09, two-tailed test). A separate sequential logistic regression analysis of predictors of a FASD diagnosis, however, indicated significantly more negative outcomes overall for girls than boys (Nagelkerke R2=0.42 for boys and 0.54 for girls, z=-2.9, p=0.004). CONCLUSION: Boys and girls had mostly similar outcomes when prenatal alcohol exposure was linked to poor physical and neurocognitive development. Nevertheless, sex ratios implicate lower viability and survival of males by first grade, and girls have more dysmorphology and neurocognitive impairment than boys resulting in a higher probability of a FASD diagnosis.

Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child Characteristics, and Maternal Risk Factors in a Second Sample of Rural Communities in South Africa.

Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods: Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results: Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 9-129 per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children in these communities. Conclusions: Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample.

BACKGROUND: The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community. METHODS: An active case ascertainment approach was employed among all first grade learners in this community (n=862). Following individual examination by clinical geneticists/dysmorphologists, cognitive/behavioral testing, and maternal interviews, final diagnoses were made in multidisciplinary case conferences. RESULTS: Physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories in a consistent, linear fashion, from severe to mild. Neurodevelopmental delays and behavioral problems were significantly worse for each of the FASD diagnostic categories, although not as consistently linear across diagnostic groups. Alcohol use was documented by direct report from the mother in 71% to 100% of cases in specific diagnostic groups. Significant distal maternal risk factors in this population are: advanced maternal age at pregnancy; low height, weight, and body mass index (BMI); small head circumference; low education; low income; and rural residence. Even when controlling for socioeconomic status, prenatal drinking correlates significantly with total dysmorphology score, head circumference, and five cognitive and behavioral measures. In this community, FAS occurs in 59-79 per 1,000 children, and total FASD in 170-233 per 1,000 children, or 17% to 23%. CONCLUSIONS: Very high rates of FASD continue in this community where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development in a significant portion of the population.

Breastfeeding and maternal alcohol use: Prevalence and effects on child outcomes and fetal alcohol spectrum disorders.

OBJECTIVE: Determine any effects that maternal alcohol consumption during the breastfeeding period has on child outcomes. METHODS: Population-based samples of children with fetal alcohol spectrum disorders (FASD), normally-developing children, and their mothers were analyzed for differences in child outcomes. RESULTS: Ninety percent (90%) of mothers breastfed for an average of 19.9 months. Of mothers who drank postpartum and breastfed (MDPB), 47% breastfed for 12 months or more. In case control analyses, children of MDPB were significantly lighter, had lower verbal IQ scores, and more anomalies in comparisons controlling for prenatal alcohol exposure and final FASD diagnosis. Utilizing a stepwise logistic regression model adjusting for nine confounders of prenatal drinking and other maternal risks, MDPB were 6.4 times more likely to have a child with FASD than breastfeeding mothers who abstained from alcohol while breastfeeding. CONCLUSIONS: Alcohol use during the period of breastfeeding was found to significantly compromise a child's development.

The continuum of fetal alcohol spectrum disorders in four rural communities in South Africa: Prevalence and characteristics.

BACKGROUND: Prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in previously unstudied rural, agricultural, lower socioeconomic populations in South Africa (ZA). METHODS: Using an active case ascertainment approach among first grade learners, 1354 (72.6%) were consented into the study via: height, weight, and/or head circumference ≤ 25th centile and/or random selection as normal control candidates. Final diagnoses were made following: examination by pediatric dysmorphologists/geneticists, cognitive/behavioral testing, and maternal risk factor interviews. RESULTS: FASD children were significantly growth deficient and dysmorphic: physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories from severe to mild to normal in a consistent, linear fashion. Neurodevelopmental delays were also significantly worse for each of the FASD diagnostic categories, although not as consistently linear across groups. Alcohol use is well documented as the proximal maternal risk factor for each diagnostic group. Significant distal maternal risk factors in this population are: low body weight, body mass, education, and income; and high gravidity, parity, and age at birth of the index child. In this low SES, highly rural region, FAS occurs in 93-128 per 1000 children, PFAS in 58-86, and, ARND in 32-46 per 1000. Total FASD affect 182-259 per 1000 children or 18-26%. CONCLUSIONS: Very high rates of FASD exist in these rural areas and isolated towns where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development.

Indicated Prevention of Fetal Alcohol Spectrum Disorders in South Africa: Effectiveness of Case Management.

In the Western Cape Province of South Africa (ZA) a subculture of binge drinking produces the highest global documented prevalence of fetal alcohol spectrum disorders (FASD). FASD prevention research activities in ZA use the Comprehensive Prevention approach from the United States Institute of Medicine. Case management (CM) was delivered as a method of indicated prevention to empower heavy drinking pregnant women to achieve cessation or a reduction in drinking. CM activities incorporated life management, Motivational Interviewing (MI) techniques and the Community Reinforcement Approach (CRA). Data were collected at baseline, 6, 12 and 18 months. Mean drinking decreases 6 months into CM; but overall alcohol consumption rose significantly over time to levels higher than baseline at 12 and 18 months. Alcohol consumption drops significantly from before pregnancy to the second and third trimesters. AUDIT scores indicate that problematic drinking decreases significantly even after the vulnerable fetus/baby was born. CM significantly increases client happiness, which correlates with reduced weekend drinking. CM was successful for women with high-risk drinking behaviour, and was effective in helping women stop drinking, or drink less, while pregnant, reducing the risk of FASD.