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Objective:To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal sociodemographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study.Methods:The DCHS comprises a population-based birth cohort of 1143 children, of which, a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n = 260) and 24 months of age (n = 734). A subset of alcohol exposed, and unexposed children was included in this analysis at age 6 months (n = 52 exposed; n = 104 unexposed) and 24 months (n = 92 exposed; n=184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development.Results:PAE was significantly associated with decreased gross motor (OR = 0.16, 95%CI 0.06-0.44, p = 0.001) or fine motor (OR = 0.16, 95%CI 0.06-0.46, p = 0.001) functioning after adjusting for maternal sociodemographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time point.Conclusion:PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occurs. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.
This study formed part of the DCHS, a multidisciplinary birth cohort study investigating the early determinants of child health (Stein et al., 2015; Zar et al., 2016; Donald et al., 2018). The DCHS enrolled pregnant women (20–28 weeks’ gestation) from two primary health care clinics, Mbekweni (a predominantly black African community) and TC Newman (a mixed-ancestry community) in the Western Cape, South Africa. Both communities are characterised by low socio-economic status (SES) and a high prevalence of multiple psychosocial risk factors (Zar et al., 2016). Pregnant women were eligible to participate if they were 18 years or older, had access to one of the two primary health care clinics for antenatal care and had stated no intention to move out of the district within the following year. Mother–child dyads were followed longitudinally until children were at least 6 years of age. This study utilised a subgroup from the DCHS. The PAE group comprised mothers with a minimum score of 11 on the alcohol questions of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST; Humeniuk et al., 2008). A follow-up cohort completed a measure on alcohol questions at 3–6 weeks and 24 months of age. Mothers were asked postpartum to provide a positive history of alcohol use in any of the three trimesters of pregnancy at levels consistent with the World Health Organization’s moderate-to-severe alcohol use. The unexposed group included children whose mothers had a score less than 11 on the ASSIST antenatally. After birth, infants identified were included for the study unless the mothers had a positive urine screen for any other drug abuse (opiates, marijuana, cocaine, methamphetamine and barbiturates). Infants born prematurely or with any other congenital malformations as well as sets of twins and triplets were excluded from the study. In total, there were 1143 live births in the DCHS (see Donald et al., 2018). A subsample of the larger cohort completed the Bayley Scales of Infant Development-III (BSID-III) at 6 months (n = 260), whereas the full cohort was invited to participate at 24 months (n = 734) making a larger sample available. At 6 and 24 months of age, a subset of infants and toddlers were selected whose mothers reported moderate-to-severe levels of alcohol consumption and for whom BSID-III data were available. Of the 260 infants, 52 were exposed to alcohol at 6 months, and of the 734 toddlers, 92 were exposed to alcohol at 24 months. The unexposed group comprised 104 at 6 months and 184 at 24 months. Unexposed control children were randomly matched for maternal education and clinic site in a 1:2 ratio (Fig. 1). Study sample selection. Participants were asked to complete self-reported and clinician-administered measures at antenatal and postnatal study visits in their preferred language, English, Afrikaans or isiXhosa. At the point of assessments (6 and 24 months of age), every effort was made to ensure a safe, anonymous, confidential and supportive environment. Translation of the measures from English to Afrikaans and isiXhosa included a standard forward and back-translation process (see Stein et al., 2015). Prior to the administration of the measures, adult mothers or legal guardians of the children received enough information about the study and were asked to complete an informed consent form in their preferred language. Maternal socio-demographic, psychosocial and infant measures for this study have previously been described (Stein et al., 2015; Donald et al., 2018) and included: Measures included data on SES (maternal income, education, employment status and asset sum), marital status and HIV status (Myer et al., 2008). Higher scores on this validated composite score indicated higher SES. Measures included data on composite scores of maternal smoking (cigarette and cannabis use) and psychological variables (PTSD and depression) administered antenatally. Maternal smoking was assessed using the ASSIST (Humeniuk et al., 2008), maternal PTSD was assessed using the Modified Post-traumatic Stress Disorder Symptom Scale (Foa et al., 1993) and maternal depression was assessed using the Beck Depression Inventory (Beck et al., 1996). Composite scores were created for maternal smoking and psychological variables. The indicators for SES included maternal income, education, employment status and asset sum; smoking included cigarette and cannabis use and psychological variables included PTSD and depression. Composite variables were used to combine data into a single score as they are considered more robust than a unidimensional measure (Field, 2013). As above, the ASSIST assessed alcohol or substance use. This measure includes seven items with scores from 0 to 10 for alcohol and 0 to 3 for illicit drugs indicating low risk, 11 to 26 for alcohol and 4 to 26 for illicit drugs indicating moderate risk, and above 26 as high risk of severe problems, with the likelihood of alcohol dependence (Group, 2002). The higher the score, the greater the alcohol-related risk. The ASSIST has good reliability and validity in several countries including Australia, Brazil, Ireland, India, Israel, the Palestinian Territories, Puerto Rico, the United Kingdom and Zimbabwe (Group, 2002) and in South Africa (Humeniuk et al., 2008). The BSID-III was conducted at the 6- and 24-month visits, to assess child development in infants and toddlers between 0 and 42 months (Bayley, 2006). This is an international, well-validated test that was used to measure language and motor development. The BSID-III has been standardised with a stratified sample of 1000 children ranging from 0 to 42 months that was representative of the US population with respect to gender, race/ethnicity, geographic region and parent education level having high reliability and validity (Bayley, 2006). The Bayley-III has been shown to be a reliable tool for use among the South African population (Rademeyer & Jacklin, 2013). The motor scale evaluated early fine and gross motor development (Bayley, 2006). The gross motor subset included 72 items that assessed movement of the limbs, static positioning (e.g. sitting and standing) and dynamic movement, including locomotion, coordination, balance and motor planning. The fine motor subtest included 66 items that assessed prehension, perceptual-motor integration, motor planning, speed, visual tracking, reaching, object grasping, object manipulation, functional hand skills and responses to tactile information. The motor assessments were administered using directly observed items for the infant and toddler (Bayley, 2006). The language scale assessed receptive and expressive communication and was directly administered to the infant or toddler (Bayley, 2006). The receptive communication subtest includes 49 items that assessed pre-verbal behaviour, vocabulary development (identifying objects and pictures), understanding morphological development (pronouns and prepositions), morphological markers (e.g. plural, tense markings and the possessive), social referencing and verbal comprehension (Bayley, 2006). The expressive communication subtest included 48 items that assessed pre-verbal communication (babbling and gesturing), vocabulary development (naming objects, pictures or naming attributes) and morpho-syntactic development. Composite scores were based on the composite equivalents of the scaled scores. Scaled scores were based on scores with a mean of 10 and a standard deviation of 3 and range from 1 to 19. At 6 months, scaled scores were corrected for prematurity. The assessors were trained by a paediatric neurologist who ensured quality control and scoring precision. A trained paediatric occupational therapist or physiotherapist administered the BSID-III scales in the home language of the infants and toddlers. The assessors had background experience in paediatric clinical and research environments and were blinded to the exposure status of the children. The DCHS was approved by the Faculty of Health Sciences Human Research Ethics Committees of the University of Cape Town and Stellenbosch University in South Africa, and by the Western Cape Department of Health Provincial Research Committee. All study participants provided written informed consent. The data were analysed using descriptive statistics which included frequencies and percentages for categorical data, while means (SD) were presented for normally distributed data. Medians [interquartile range (IQR)] were presented for data that were not normally distributed and for all BSID-III scores. For comparisons between alcohol-exposed and -unexposed children, chi-squared tests were used for categorical variables, while t-tests or, in the case of data that were not normally distributed, Mann–Whitney U-test was used. Variables that were associated with PAE at an alpha level of 0.05 or less were included in the final model to determine whether the outcome measures that were significantly associated with PAE remained significant after adjusting for potential confounders (see Appendices A and B). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development. The model was adjusted for the maternal socio-demographic and psychosocial confounding variables, which are known to be associated with child neurodevelopment (motor, language and cognitive outcomes). Potential confounding variables included composites of SES (Fried & Watkinson, 1988), smoking (cigarette and cannabis) and psychological variables (Fried & Watkinson, 1990), and child’s body mass index (BMI) z-score and child’s nutritional status according to their gender and age. Significance was set at 0.05, and 95% confidence intervals (CIs) were reported for all estimates, where applicable.
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