Changes in drinking patterns during and after pregnancy among mothers of children with fetal alcohol syndrome: A study in three districts of South Africa.

BACKGROUND: Mixed ancestry populations in South Africa have amongst the highest rates of fetal alcohol syndrome (FAS) worldwide. Defining the drinking patterns of women with a FAS child guides FAS preventive interventions. METHODS: Data were drawn from FAS prevalence surveys conducted in three districts: Witzenberg (Cape Winelands), Frances Baard (inland mining town) and Saldanha Bay (coastal towns). 156 mothers and 50 proxy informants of school-entry children diagnosed with FAS and partial-FAS were interviewed, and compared with 55 controls recruited in Saldanha Bay. RESULTS: Study participants were of low socio-economic status (SES), and a majority of children were either in foster care (12%) or had been cared for by relatives for long periods (44%). Of cases, 123/160 (77%) reported current drinking, similar between sites. During pregnancy, only 35% (49/139) of cases had stopped drinking, varying between sites (from 21% to 54% in chronological order of surveys; p<0.001), while 6% (7/109) increased drinking. Though many women who stopped in pregnancy resumed postpartum, cessation in pregnancy was strongly associated with discontinuation in the long run (OR=3.3; 95%CI=1.2-8.9; p=0.005). At interview, 36% of cases (54/151) and 18% of controls (9/51) were at risk of an alcohol-exposed pregnancy (p=0.02). Median maternal mass of cases was 22kg lower than controls, with 20% being underweight and 14% microcephalic. CONCLUSIONS: Increasing rates of drinking cessation during pregnancy over time suggest rising awareness of FAS. Cessation is associated with recidivism after pregnancy but also with reduced long-term drinking. Interventions should target alcohol abstinence in pregnancy, but extend into the puerperium.

Design, construction, and testing of a stereo-photogrammetric tool for the diagnosis of fetal alcohol syndrome in infants.

Stereo-photogrammetry provides a low cost, easy to use, and noninvasive alternative to traditional facial anthropometry for the diagnosis of fetal alcohol syndrome (FAS). We describe such a system for use in obtaining 3-D facial information in infants. The infant is photographed using three high resolution digital cameras simultaneously while seated in a car seat. The subject's head is enclosed in a control frame during imaging. Technical system tests, namely control frame interpolation, camera calibration reliability, and camera synchronization delay assessments were performed. Direct and stereo-photogrammetric measurements of a doll were compared. Of 275 inter-landmark distances, 100% were within a 1.5 mm error range and 92.36% within a 1 mm error range when the two modalities were compared. Stereo-photogrammetry proved to be highly precise with submillimeter error in landmark placement for all landmarks on the doll. An intra-modality comparison of inter-landmark distances using two sets of images of five subjects showed the stereo-photogrammetric system to be highly reliable, with an average 72.25% of distances within a 1 mm error range. The system has potential for large scale screening and surveillance studies for FAS.

Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: a third study.

OBJECTIVES: This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. METHODS: In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. RESULTS: Significant differences were found between the mothers of FASD children and controls in socio-economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS-producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The child's total dysmorphology score correlates significantly with mother's weight (-0.46) and BMI (-0.39). Bivariate correlations are significant between the child's dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partner's alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the child's verbal IQ, non-verbal IQ and behavioral problems. CONCLUSIONS: Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.

The epidemiology of fetal alcohol syndrome and partial FAS in a South African community.

OBJECTIVES: The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) were determined in a third primary school cohort in a community in South Africa (SA). METHODS: An active case ascertainment, two-tier screening methodology, and the revised Institute of Medicine diagnostic criteria were employed among 818 first grade pupils. Characteristics of children with FAS and PFAS are contrasted with a randomly selected control group. Data were collected and analyzed for children in the study regarding: (1) physical growth and development, including dysmorphology, (2) intelligence and behavioral characteristics, and (3) their mother's social, behavioral, and physical characteristics. RESULTS: The rate of FAS and PFAS in this area continues as the highest reported in any overall community and is much higher than rates elsewhere. In this cohort it is 68.0-89.2 per 1000. Severe episodic drinking on weekends among mothers of children with FAS and PFAS accounts for 96% of all alcohol consumed. Various measures of maternal drinking are significantly correlated with negative outcomes of children in the areas of non-verbal intelligence (-0.26), verbal intelligence (-0.28), problem behavior (0.31), and overall dysmorphology score (0.59). Significantly more FAS and PFAS exists among children of rural residents (OR=3.79). CONCLUSIONS: A high rate of FAS and PFAS was again documented in this community, and it has increased. Given population similarities, we suspect that other communities in the Western Cape Province of South Africa also have high rates. Programs for prevention are needed.

Letter and category fluency in children with fetal alcohol syndrome from a community in South Africa.

OBJECTIVE: This study investigated whether there were differential effects of substantial prenatal alcohol exposure on letter and category fluency in children. Given that children with prenatal alcohol exposure are often impaired in executive functioning and that letter fluency taxes executive processes more than category fluency, it was expected that children with fetal alcohol syndrome (FAS) would be more impaired in letter than in category fluency. A second objective of the study was to examine the developmental trends in the two types of fluency in children with prenatal alcohol exposure. It was hypothesized that between the ages of 6 and 9 years, these FAS children would show age-related changes in category fluency but not in letter fluency. METHOD: As part of a neuropsychological test battery designed for an international collaborative study of FAS in South Africa, tests of letter and category fluency were administered in Afrikaans. The participants were 62 children with FAS and 61 controls matched with respect to age, gender (58 boys and 65 girls), ethnicity, and socioeconomic status. RESULTS: Results showed that the FAS group had relatively greater difficulty with letter fluency than with category fluency and that the FAS group generated fewer words in both fluency conditions. Contrary to the expectation, however, alcohol-affected children demonstrated age-related linear trends in both letter and category fluency. CONCLUSIONS: This is the first study of verbal fluency involving a large sample of well-diagnosed children with FAS conducted in a nonwestern environment. The results are nonetheless consistent with those obtained in western countries in studies of children with various levels of prenatal alcohol exposure and various levels of fetal alcohol spectrum disorder. This study suggests that at least some aspects of the cognitive profile associated with prenatal alcohol exposure may be generalizable across cultural and ethnic boundaries.

Eye measurements in 7-year-old black South African children.

BACKGROUND: Ethnic variation often renders anthropometric reference values obtained in one population unsuitable for use in others. Fetal alcohol syndrome (FAS) diagnosis relies in part on the evaluation of certain anthropometric facial features. Measurements of these facial features in South African children have not been compared with measurements obtained in other populations. AIM: The study seeks to determine the suitability of reference values obtained in other populations for the diagnosis of the facial phenotype associated with FAS in South African children. PARTICIPANTS AND METHODS: Palpebral fissure length (PFL), interpupillary distance (IPD), inner canthal distance (ICD) and outer canthal distance (OCD) measured in a group of black South African children were obtained from digital photographs using stereophotogrammetry, and compared with measurements published for other populations. The study population comprised 17 7-year-old boys and 17 7-year-old girls. The precision and reliability of measurements were examined with reference to published data. RESULTS: Eye distance measurements in the study population do not consistently reflect those in any one other population for which such measurements have been published. CONCLUSION: Population-specific reference values of eye distance measurements should be established for South African children.

Fetal alcohol syndrome epidemiology in a South African community: a second study of a very high prevalence area.

OBJECTIVE: The aim of the study was to determine the prevalence and characteristics of fetal alcohol syndrome (FAS) in a second primary school cohort in a community in South Africa. METHOD: Active case ascertainment, two-tier screening, and Institute of Medicine assessment methodology were employed among 857 first grade pupils, most born in 1993. Characteristics of children with FAS were contrasted with characteristics of a randomly selected control group from the same classrooms. Physical growth and development, dysmorphology and psychological characteristics of the children and measures of maternal alcohol use and smoking were analyzed. RESULTS: The rate of FAS found in this study is the highest yet reported in any overall community in the world, 65.2-74.2 per 1,000 children in the first grade population. These rates are 33-148 times greater than U.S. estimates and higher than in a previous cohort study in this same community (40.5-46.4 per 1,000). Detailed documentation of physical features indicates that FAS children in South Africa have characteristics similar to those elsewhere: poor growth and development, facial and limb dysmorphology, and lower intellectual functioning. Frequent, severe episodic drinking of beer and wine is common among mothers and fathers of FAS children. Their lives are characterized by serious familial, social and economic challenges, compared with controls. Heavy episodic maternal drinking is significantly associated with negative outcomes of children in the area of nonverbal intelligence but even more so in verbal intelligence, behavior and overall dysmorphology (physical anomalies). Significantly more FAS exists among children of women who were rural residents (odds ratio: 7.36, 95% confidence interval: 3.31-16.52), usually among workers on local farms. CONCLUSION: A high rate of FAS was documented in this community. Given social and economic similarities and racial admixture, we suspect that other communities in the Western Cape have rates that also are quite high.

Maternal risk factors for fetal alcohol syndrome in the Western cape province of South Africa: a population-based study.

OBJECTIVES: We defined risk factors for fetal alcohol syndrome (FAS) in a region with the highest documented prevalence of FAS in the world. METHODS: We compared mothers of 53 first-grade students with FAS (cases) with 116 randomly selected mothers of first-grade students without FAS (controls). RESULTS: Differences between case and control mothers in our study population existed regarding socioeconomic status, religiosity, education, gravidity, parity, and marital status. Mothers of children with FAS came from alcohol-abusing families in which heavy drinking was almost universal; control mothers drank little to no alcohol. Current and past alcohol use by case mothers was characterized by heavy binge drinking on weekends, with no reduction of use during pregnancy in 87% of the mothers. Twenty percent of control mothers drank during pregnancy, a rate that declined to 12.7% by the third trimester. The percentage who smoked during pregnancy was higher for case mothers than for control mothers (75.5% vs 30.3%), but the number of cigarettes smoked was low among case mothers. The incidence of FAS in offspring of relatively young women (28 years) was not explained by early drinking onset or years of drinking (mean, 7.6 years among case mothers). In addition to traditional FAS risk factors, case mothers were smaller in height, weight, head circumference, and body mass index, all anthropomorphic measures that indicate poor nutrition and second-generation fetal alcohol exposure. CONCLUSIONS: Preventive interventions are needed to address maternal risk factors for FAS.

A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 institute of medicine criteria.

BACKGROUND: The adverse effects of alcohol on the developing human represent a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). The first descriptions in the modern medical literature of a distinctly recognizable pattern of malformations associated with maternal alcohol abuse were reported in 1968 and 1973. Since that time, substantial progress has been made in developing specific criteria for defining and diagnosing this condition. Two sets of diagnostic criteria are now used most widely for evaluation of children with potential diagnoses in the FASD continuum, ie, the 1996 Institute of Medicine (IOM) criteria and the Washington criteria. Although both approaches have improved the clinical delineation of FASD, both suffer from significant drawbacks in their practical application in pediatric practice. OBJECTIVE: The purpose of this report is to present specific clarifications of the 1996 IOM criteria for the diagnosis of FASD, to facilitate their practical application in clinical pediatric practice. METHODS: A large cohort of children who were prenatally exposed to alcohol were identified, through active case-ascertainment methods, in 6 Native American communities in the United States and 1 community in the Western Cape Province of South Africa. The children and their families underwent standardized multidisciplinary evaluations, including a dysmorphology examination, developmental and neuropsychologic testing, and a structured maternal interview, which gathered data about prenatal drinking practices and other demographic and family information. Data for these subjects were analyzed, and revisions and clarifications of the existing IOM FASD diagnostic categories were formulated on the basis of the results. RESULTS: The revised IOM method defined accurately and completely the spectrum of disabilities among the children in our study. On the basis of this experience, we propose specific diagnostic criteria for fetal alcohol syndrome and partial fetal alcohol syndrome. We also define alcohol-related birth defects and alcohol-related neurodevelopmental disorder from a practical standpoint. CONCLUSIONS: The 1996 IOM criteria remain the most appropriate diagnostic approach for children prenatally exposed to alcohol. The proposed revisions presented here make these criteria applicable in clinical pediatric practice.

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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Alcohol consumption and other maternal risk factors for fetal alcohol syndrome among three distinct samples of women before, during, and after pregnancy: the risk is relative.

Data were obtained from three samples of women of childbearing age. One sample of women is from prenatal clinics serving Plains Indian women. The second sample is of women from the Plains whose children were referred to special diagnostic developmental clinics, as their children were believed to have developmental issues consistent with prenatal alcohol consumption. The third sample is of women from South Africa, each of whom has given birth to a child diagnosed with full fetal alcohol syndrome (FAS). Data across samples conform to expected trends on many variables. For example, the maternal age at time of pregnancy, a major risk factor for FAS, ranged from a mean of 23.5 years for the prenatal clinic sample, to 23.8 years for the developmental clinic sample, to 27.6 for the sample of women who have delivered children with FAS. Other variables of maternal risk for FAS expected from the extant literature, such as high gravidity and parity, binge drinking, heavy intergenerational drinking in the mother's extended family and immediate social network, and length of drinking career, were compared across the three samples with variable results. However, normative measures of drinking problems are unreliable when reported across cultures. An unexpected finding from this three-sample comparison was the differential risk found when comparing U.S. women to South African women. Women in the U.S. Plains Indian samples report a high consumption of alcohol in a binge pattern of drinking, yet there is less detectable damage to the fetus than among the South African women. Body mass index (BMI) and lifelong and current nutrition may have a substantial impact, along with the above factors, in relative risk for an FAS birth. The level of risk for producing a child with FAS is influenced by environmental and behavioral conditions that vary between populations and among individual women. Also, because many syndromes are genetically based, there is a need for full behavioral and genetic histories of the mother, family, and child being studied. Collecting extensive behavioral information as well as genetic histories will provide the requisite information for making an accurate diagnosis of FAS.

Validation of a new biomarker of fetal exposure to alcohol.

OBJECTIVE: To test the sensitivity and specificity of fatty acid ethyl esters (FAEEs) extracted from meconium to identify alcohol-using pregnant women with a sensitive and specific methodology, gas chromatography-tandem mass spectroscopy (GC/MS/MS). Study design Twenty-seven samples of meconium were obtained from infants from the mixed race community in Cape Town, South Africa, who were enrolled in a longitudinal neurobehavioral study. Maternal alcohol use was reported prospectively during pregnancy. FAEEs were isolated from meconium and quantitated by GC/MS/MS. RESULTS: Ethyl oleate was the FAEE that correlated most strongly with maternal self-reported drinking, especially with the average ounces of absolute alcohol ingested per drinking day. Ethyl oleate was most strongly related to drinking in the second and third trimesters (Pearson r=.55 and.40, respectively). At a threshold of 1.5 average ounces of absolute alcohol ingested per drinking day, the area under the receiving operator characteristic curve was.92 (95% confidence interval, 0.74-0.97). Using a cut-off value of 32 ng/g, sensitivity was 84.2% and specificity was 83.3%. CONCLUSIONS: Ethyl oleate concentration in meconium assayed by GC/MS/MS provides a highly sensitive and specific indicator of maternal alcohol use during pregnancy.

Role of depth in eye distance measurements: comparison of single and stereo-photogrammetry.

Photogrammetry has been used as an alternative to direct measurements to obtain facial distances for a variety of anthropometric applications. Taking measurements from photographs is less intrusive to subjects and reduces screening time, but measurements from single frontal photographs neglect depth information and may be inadequate for screening purposes. This study examined the role of depth in measurements of palpebral fissure length, interpupillary distance, inner canthal distance, and outer canthal distance using single- and stereo-photogrammetry; an operator selected landmarks on single and stereo digital photographs displayed on a computer monitor. Depth was not found to make a significant contribution to eye distances in an idealized system where the real-world coordinates of points on the eye were known from three-dimensional calibration of stereo photographs. However, the differences found between measurements taken from single frontal photographs and those from stereo-photogrammetry indicated that measurements from single photographs are prone to errors due to misalignment of the camera, the face, and the calibration instrument during image acquisition; if single photographs are to be used, the placement of these components should be carefully monitored.

Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa.

Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners. A previous report has suggested that a founder effect may explain the higher prevalence of PXE in Afrikaners, a European-derived population that first settled in South Africa in the 17th century. To investigate this hypothesis, we performed haplotype and mutational analysis of DNA from 24 South African families of Afrikaner, British and Indian descent. Among the 17 Afrikaner families studied, three common haplotypes and six different disease-causing variants were identified. Three of these mutant alleles were missense variants, two were nonsense mutations and one was a single base-pair insertion. The most common variant accounted for 53% of the PXE alleles, whereas other mutant alleles appeared at lower frequencies ranging from 3% to 12%. Haplotype analysis of the Afrikaner families showed that the three most frequent mutations were identical-by-descent, indicating a founder origin of PXE in this population.