Identifying and Validating Alcohol Diagnostics for Injury-Related Trauma in South Africa: Protocol for a Mixed Methods Study.

BACKGROUND: The burden of alcohol use among patients with trauma and the relative injury risks is not routinely measured in South Africa. Given the prominent burden of alcohol on hospital trauma departments, South Africa needs practical, cost-effective, and accurate alcohol diagnostic tools for testing, surveillance, and clinical management of patients with trauma. OBJECTIVE: This study aims to validate alcohol diagnostics for injury-related trauma and assess its use for improving national health practice and policy. METHODS: The Alcohol Diagnostic Validation for Injury-Related Trauma study will use mixed methods across 3 work packages. Five web-based focus group discussions will be conducted with 6 to 8 key stakeholders, each across 4 areas of expertise (clinical, academic, policy, and operational) to determine the type of alcohol information that will be useful for different stakeholders in the injury prevention and health care sectors. We will then conduct a small pilot study followed by a validation study of alcohol diagnostic tools (clinical assessment, breath analysis, and fingerprick blood) against enzyme immunoassay blood concentration analysis in a tertiary hospital trauma setting with 1000 patients. Finally, selected alcohol diagnostic tools will be tested in a district hospital setting with a further 1000 patients alongside community-based participatory research on the use of the selected tools. RESULTS: Pilot data are being collected, and the protocol will be modified based on the results. CONCLUSIONS: Through this project, we hope to identify and validate the most appropriate methods of diagnosing alcohol-related injury and violence in a clinical setting. The findings from this study are likely to be highly relevant and could influence our primary beneficiaries-policy makers and senior health clinicians-to adopt new practices and policies around alcohol testing in injured patients. The findings will be disseminated to relevant national and provincial government departments, policy experts, and clinicians. Additionally, we will engage in media advocacy and with our stakeholders, including community representatives, work through several nonprofit partners to reach civil society organizations and share findings. In addition, we will publish findings in scientific journals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52949.

Perceptions of perinatal alcohol use and treatment needs in Cape Town, South Africa: a qualitative study.

Background: South Africa has one of the world's highest rates of foetal alcohol spectrum disorders (FASD). Recent evidence also showed that alcohol use during lactation significantly compromises child development in children exposed to alcohol through breastfeeding, independent of prenatal alcohol exposure. This study explored perceptions of perinatal alcohol use and treatment needs in Cape Town, South Africa, to inform the development of an intervention to encourage alcohol abstinence during pregnancy and breastfeeding. Methods: Individual in-depth interviews (IDIs) were conducted with women who were pregnant with a recent history of alcohol use (n=32) and clinic and community stakeholders (n=16). Interviews were audio recorded and transcribed verbatim. Coding and thematic analyses were conducted in NVivo 12. Results: Results indicate widespread perception that women know the dangers of drinking alcohol while pregnant with much less known about drinking while breastfeeding. Mixed views were shared about whether women who are pregnant or breastfeeding experience alcohol-related stigma. Participants described contextual factors impacting drinking that include interpersonal violence, lack of support, stress, anxiety and poverty, and drinking being normalised. Finally, participants had mixed views and conflicting knowledge of available resources to support alcohol reduction and highlighted a desire for support groups and the involvement of partners in alcohol interventions. Conclusions: Findings from this study highlight the need for an alcohol intervention programme that is innovative and tailored to the needs of women who are pregnant or postpartum. It also highlights the importance of including community-based support and partner involvement in these interventions.

Epidemiology of alcohol use and alcohol use disorders among people living with HIV on antiretroviral therapy in Northwest Tanzania: implications for ART adherence and case management.

Alcohol use disorders (AUD) among people living with HIV (PLHIV) are associated with poor health outcomes. This cross-sectional study examined current alcohol use and AUD among 300 PLHIV on ART at four HIV care centres in Northwest Tanzania. Participants' data were collected using questionnaires. Alcohol use was assessed using Alcohol Use Disorders Identification Test (AUDIT). Logistic regression was used to examine associations between each outcome (current drinking and AUD) and sociodemographic and clinical factors. Association between alcohol use and ART adherence was also studied. The median age of participants was 43 years (IQR 19-71) and 41.3% were male. Twenty-two (7.3%) participants failed to take ART at least once in the last seven days. The prevalence of current drinking was 29.3% (95% CI 24.2-34.8%) and that of AUD was 11.3% (8.2%-15.5%). Males had higher odds of alcohol use (OR 3.03, 95% CI 1.79-5.14) and AUD (3.89, 1.76-8.60). Alcohol use was associated with ART non-adherence (OR = 2.78, 1.10-7.04). There was a trend towards an association between AUD and non-adherence (OR = 2.91, 0.92-9.21). Alcohol use and AUD were common among PLHIV and showed evidence of associations with ART non-adherence. Screening patients for alcohol use and AUD in HIV clinics may increase ART adherence.

Does Reducing Alcohol Use Among People with HIV Alleviate Psychological Distress and Symptoms of Depression? A Randomized Controlled Trial in Tshwane, South Africa.

Although alcohol use is associated with depression, it is unclear if brief alcohol reduction interventions can ameliorate depression and psychological distress among people with HIV (PWH). We use data from a two-arm randomised controlled trial to examine this question. PWH on antiretroviral treatment (ART) were randomly assigned to receive a brief intervention or treatment as usual (n = 622). Screening was done with the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-C, Centre for Epidemiological Studies Depression inventory and Kessler Psychological Distress Scale, at baseline and at 3- and 6-months post-baseline. Changes in depression and psychological distress was assessed using analysis of covariance models with baseline measures of alcohol consumption, sex and age included as covariates and adjusting for baseline symptom severity. Changes in alcohol consumption between baseline and follow-up were included in the analysis to establish if this affected outcomes. For both the intervention and control groups, there were significant reductions in symptom severity at 3-months and 6-months for depression and psychological distress, but no significant between group differences were observed. Reductions in alcohol consumption were significantly associated with reductions in depression and psychological distress, supporting the hypothesis that alcohol use is linked to depression among PWH.Trial Registration Pan African Clinical Trials Register, PACTR201405000815100.nh.

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.

Alcohol diagnostic validation for injury-related trauma: Findings from a pilot study.

Introduction: Alcohol consumption is a key driver of the burden of violence and injury in South Africa (SA). Hence, we aim to validate various alcohol assessment tools against a blood test to assess their utility for improving national health practice and policy. Methods: We conducted a cross-sectional pilot study from 3 to 19 August 2022 at Groote Schuur Hospital in Cape Town, SA. This was to test logistics for the time of venous blood centrifugation and validation of alcohol assessment tools used in injured patients ahead of the main validation study. Adults aged 18 years and older, who were injured <8 h before arrival were included. Consent was obtained for venous blood alcohol testing to validate, as the gold standard, against the following: active- and passive breath alcohol testing, clinical screening and a finger prick test. Descriptive statistics were reported for the pilot study. Results: The active breath alcohol test's digital reading and the passive test's 'yes/no' results corresponded well against the venous blood alcohol results. The average time to centrifugation was within the laboratory's 2-h cut-off requirement to preserve the alcohol in the serum. Discussion and Conclusion: The pilot study was helpful in identifying challenges with one of the alcohol assessment tools and prevented further costs ahead of the main validation study. We also determined that the selected tertiary hospital site caused a delay in recruiting eligible patients due to other hospital referrals. Hence, the main validation study is in progress at a district-level hospital for a larger sample of eligible patients for testing.

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.

Efficacy of alcohol reduction interventions among people with HIV as evaluated by self-report and a phosphatidylethanol (PEth) outcome: protocol for a systematic review and individual participant data meta-analysis.

INTRODUCTION: Unhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone. METHODS AND ANALYSIS: We will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias. ETHICS AND DISSEMINATION: The study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings. PROSPERO REGISTRATION NUMBER: CRD42022373640.

Motivational interviewing and problem-solving therapy intervention for patients on antiretroviral therapy for HIV in Tshwane, South Africa: A randomized controlled trial to assess the impact on alcohol consumption.

BACKGROUND AND AIMS: Reduction of alcohol consumption is important for people undergoing treatment for HIV. We tested the efficacy of a brief intervention for reducing the average volume of alcohol consumed among patients on HIV antiretroviral therapy (ART). DESIGN, SETTING AND PARTICIPANTS: This study used a two-arm multi-centre randomized controlled trial with follow-up to 6 months. Recruitment occurred between May 2016 and October 2017 at six ART clinics at public hospitals in Tshwane, South Africa. Participants were people living with HIV, mean age 40.8 years [standard deviation (SD) = 9.07], 57.5% female, and on average 6.9 years (SD = 3.62) on ART. At baseline (BL), the mean number of drinks consumed over the past 30 days was 25.2 (SD = 38.3). Of 756 eligible patients, 623 were enrolled. INTERVENTION: Participants were randomly assigned to a motivational interviewing (MI)/problem-solving therapy (PST) intervention arm (four modules of MI and PST delivered over two sessions by interventionists) or a treatment as usual (TAU) comparison arm. People assessing outcomes were masked to group assignment. MEASUREMENTS: The primary outcome was the number of standard drinks (15 ml pure alcohol) consumed during the past 30 days assessed at 6-month follow-up (6MFU). FINDINGS: Of the 305 participants randomized to MI/PST, 225 (74%) completed the intervention (all modules). At 6MFU, retention was 88% for the control and 83% for the intervention arm. In support of the hypothesis, an intention-to-treat-analysis for the primary outcome at 6MFU was -0.410 (95% confidence interval = -0.670 to -0.149) units lower on log scale in the intervention group than in the control group (P = 0.002), a 34% relative reduction in the number of drinks. Sensitivity analyses were undertaken for patients who had alcohol use disorders identification test (AUDIT) scores ≥ 8 at BL (n = 299). Findings were similar to those of the whole sample. CONCLUSIONS: In South Africa, a motivational interviewing/problem-solving therapy intervention significantly reduced drinking levels in HIV-infected patients on antiretroviral therapy at 6-month follow-up.

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).

Effective alcohol policies are associated with reduced consumption among demographic groups who drink heavily.

BACKGROUND: Alcohol policies stand out among other noncommunicable disease-relevant policies for the lack of uptake. Composite indicators have been developed to measure the effects of alcohol control policy. We investigated whether drinking patterns among demographic groups from general population samples of drinkers from diverse countries are associated with alcohol control policy as measured by the International Alcohol Control (IAC) Policy Index. METHODS: Representative samples of adult drinkers from 10 countries (five high-income and five middle-income) were surveyed about alcohol consumption, using beverage and location-specific questions. MEASUREMENTS: The IAC Policy Index was analyzed with frequency, typical occasion quantity, and volume consumed. Analyses used mixed models that included interactions between country IAC Policy Index score and age group, gender, and education level. FINDINGS: Each increase in IAC policy index score (reflecting more effective alcohol policy) was associated with a 13.9% decrease in drinking frequency (p = 0.006) and a 16.5% decrease in volume (p = 0.001). With each increase in IAC Policy Index score, both genders decreased for all three measures, but men less so than women. Women decreased their typical occasion quantity by 1.2% (p = 0.006), frequency by 3.1% (p < 0.001), and total volume by 4.2% (p < 0.001) compared to men. Low and mid-education groups decreased their typical occasion quantity by 2.6% (p < 0.001) and 1.6% (p = 0.001), respectively, compared to high education, while for drinking frequency the low education group increased by 7.0% (p < 0.001). There was an overall effect of age (F = 19.27, p < 0.0001), with 18-19 and 20-24-year-olds showing the largest decreases in typical occasion quantity with increasing IAC policy index score. CONCLUSIONS: The IAC Policy Index, reflecting four effective policies, was associated with volume and frequency of drinking across 10 diverse countries. Each increase in the IAC Policy Index was associated with lower typical quantities consumed among groups reporting heavy drinking: young adults and less well-educated. There is value in implementing such alcohol policies and a need to accelerate their uptake globally.

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.

Self-reported alcohol use versus phosphatidylethanol in behavioral trials: A study of people living with HIV in Tshwane, South Africa.

BACKGROUND: Accurately quantifying alcohol use among persons with HIV (PWH) is important for validly assessing the efficacy of alcohol reduction interventions. METHODS: We used data from a randomized controlled trial of an intervention to reduce alcohol use among PWH who were receiving antiretroviral therapy in Tshwane, South Africa. We calculated agreement between self-reported hazardous alcohol use measured by the Alcohol Use Disorders Identification Test (AUDIT; score ≥8) and AUDIT-Consumption (AUDIT-C; score ≥3 for females and ≥4 for males), heavy episodic drinking (HED) in the past 30 days, and heavy drinking in the past 7 days with a gold standard biomarker--phosphatidylethanol (PEth) level (≥50 ng/mL)--among 309 participants. We used multiple logistic regression to assess whether underreporting of hazardous drinking (AUDIT-C vs. PEth) differed by sex, study arm, and assessment time point. RESULTS: Participants' mean age was 40.6 years, 43% were males, and 48% were in the intervention arm. At 6 months, 51% had PEth ≥50 ng/mL, 38% and 76% had scores indicative of hazardous drinking on the AUDIT and AUDIT-C, respectively, 11% reported past 30-day HED, and 13% reported past 7-day heavy drinking. At 6 months, there was low agreement between AUDIT-C scores and past 7-day heavy drinking relative to PEth ≥50 (sensitivities of 83% and 20% and negative predictive values of 62% and 51%, respectively). Underreporting of hazardous drinking at 6 months was associated with sex (OR = 3.504. 95% CI: 1.080 to 11.364), with odds of underreporting being greater for females. CONCLUSIONS: Steps should be taken to decrease underreporting of alcohol use in clinical trials.

Effective alcohol policies and lifetime abstinence: An analysis of the International Alcohol Control policy index.

INTRODUCTION: Alcohol abstinence remains common among adults globally, although low and middle-income countries are experiencing declines in abstention. The effect of alcohol policies on lifetime abstinence is poorly understood. The International Alcohol Control (IAC) policy index was developed to benchmark and monitor the uptake of effective alcohol policies and has shown strong associations with alcohol per capita consumption and drinking patterns. Uniquely, the index incorporates both policy 'stringency' and 'impact', reflecting policy implementation and enforcement, across effective policies. Here we assessed the association of the IAC policy index with lifetime abstinence in a diverse sample of jurisdictions. METHODS: We conducted a cross-sectional analysis of the relationship between the IAC policy index score, and its components, and lifetime abstinence among adults (15+ years) in 13 high and middle-income jurisdictions. We examined the correlations for each component of the index and stringency and impact separately. RESULTS: Overall, the total IAC policy index scores were positively correlated with lifetime abstinence (r = 0.76), as were both the stringency (r = 0.62) and impact (r = 0.82) scores. Marketing restrictions showed higher correlations with lifetime abstinence than other policy domains (r = 0.80), including restrictions on physical availability, pricing policies and drink-driving prevention. DISCUSSION AND CONCLUSION: Our findings suggest that restricting alcohol marketing could be an important policy for the protection of alcohol abstention. The IAC policy index may be a useful tool to benchmark the performance of alcohol policy in supporting alcohol abstention in high and middle-income countries.

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.

Hazardous drinking and alcohol use disorders.

Alcohol is one of the most widely consumed psychoactive drugs globally. Hazardous drinking, defined by quantity and frequency of consumption, is associated with acute and chronic morbidity. Alcohol use disorders (AUDs) are psychiatric syndromes characterized by impaired control over drinking and other symptoms. Contemporary aetiological perspectives on AUDs apply a biopsychosocial framework that emphasizes the interplay of genetics, neurobiology, psychology, and an individual's social and societal context. There is strong evidence that AUDs are genetically influenced, but with a complex polygenic architecture. Likewise, there is robust evidence for environmental influences, such as adverse childhood exposures and maladaptive developmental trajectories. Well-established biological and psychological determinants of AUDs include neuroadaptive changes following persistent use, differences in brain structure and function, and motivational determinants including overvaluation of alcohol reinforcement, acute effects of environmental triggers and stress, elevations in multiple facets of impulsivity, and lack of alternative reinforcers. Social factors include bidirectional roles of social networks and sociocultural influences, such as public health control strategies and social determinants of health. An array of evidence-based approaches for reducing alcohol harms are available, including screening, pharmacotherapies, psychological interventions and policy strategies, but are substantially underused. Priorities for the field include translating advances in basic biobehavioural research into novel clinical applications and, in turn, promoting widespread implementation of evidence-based clinical approaches in practice and health-care systems.

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.