Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to ...contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities.
The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning <R1,000 per month), and high prevalence of maternal psychosocial risk factors including alcohol use in pregnancy (n = 95; 14.5%), smoking (n = 241; 34.7%), depression (n = 156; 23.7%), lifetime intimate partner violence (n = 310; 47.3%), and history of maternal childhood trauma (n = 228; 34.7%). A high proportion of children were categorised as delayed (defined by scoring < -1 standard deviation below the mean scaled score calculated using the BSID-III norms from a United States population) in different domains (369 50.5% cognition, 402 55.6% receptive language, 389 55.4% expressive language, 169 23.2% fine motor, and 267 38.4% gross motor). Four hundred five (55.3%) children had >1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition β = -0.74; 95% CI -1.46 to -0.03, p = 0.042, receptive language β = -1.10; 95% CI -1.70 to -0.49, p < 0.001, expressive language β = -1.65; 95% CI -2.46 to -0.84, p < 0.001, and fine motor β = -0.70; 95% CI -1.20 to -0.20, p = 0.006 scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitations of the study include attrition of sample from birth to assessment age and missing data in some exposure areas from those assessed.
This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group.
There are approximately 16 million children who are HIV-exposed and uninfected (CHEU) worldwide. Studies suggest that CHEU are at risk for developmental impairment in infancy, particularly in ...language domains. However, there is limited research examining neurocognitive function in CHEU older than 2 years, including important pre-school years. This study aimed to investigate associations between HIV exposure without infection and neurocognitive outcomes and to determine risk factors for neurodevelopment in CHEU at age 3-4 years.
The Drakenstein Child Health Study is a South African population-based birth cohort which enrolled women in pregnancy with ongoing follow up. Neurocognitive outcomes were assessed in children at 3.5 years by trained assessors blinded to HIV status including general cognitive function, language, and memory, measured using the Kaufmann Assessment Battery for Children, Second Edition (KABC-II). Data were compared between CHEU and children who were HIV-unexposed uninfected (CHUU) using multivariable logistic and linear regression, including testing for effect modification; sex-stratified risk factor analyses were performed.
A total of 497 children were included (97 20% CHEU; 400 80% CHUU; 50% male), with a mean age of 3.5 years (range 3.4-3.6). Groups had similar birth and household characteristics, although mothers of CHEU were older, on average. Overall, CHEU had lower expressive language scores compared to CHUU on unadjusted and adjusted analyses (effect size: -0.23 95% CI -0.45, -0.01). There were no group differences in general cognitive or memory function (p>0.05). On sex-stratified analyses, male CHEU were found to have higher odds of suboptimal cognitive development compared to male CHUU (aOR 2.28 95% CI 1.06, 4.87, p = 0.034). Several other factors including birthweight, maternal education, maternal ART duration and HIV viral load during pregnancy were associated with cognition, memory, or expressive language outcomes in CHEU, dependent on child sex.
The findings suggest that perinatal HIV exposure continues to be associated with impaired language development across the preschool years, highlighting the importance of targeting early interventions to optimise language outcomes. Further, the results suggest the importance of demographic, biological and HIV-related variables influencing developmental outcomes in CHEU. The greater risk of suboptimal cognitive development in male CHEU requires investigation around sex-specific mechanisms.
Violence against women remains a significant public health problem globally. The majority of longitudinal studies documenting the negative impact of intimate partner violence (IPV) on the mental ...health of women come from high-income countries. The aim of this study was to investigate the longitudinal association between emotional, physical, or sexual IPV and depression symptoms among South African women in a prospective cohort study. Participants were 981 South African women enrolled in the Drakenstein Child Health Study—a cohort study investigating the early life determinants of child health. Interview data from four time-points (antenatal care visit, 6 months, 12 months, and 18 months postpartum) were included. The primary independent variable was self-reported emotional, physical, and sexual IPV in the past 12 months. Depressive symptoms were assessed at each time-point with the Edinburgh Postnatal Depression Scale (EPDS); a cutoff score of ⩾13 was used to define significant depression symptoms. We used pooled-multivariable logistic regression models to determine associations between the three different forms of IPV and significant depression symptoms while adjusting for time-fixed and time-updated covariates. The mean age of the sample at antenatal care visit was 27 years (standard deviation = 6.0). In the adjusted model including all forms of IPV and adjusting for sociodemographic and clinical characteristics, substance use, and childhood trauma, emotional (adjusted odds ratio aOR =1.55, 95% confidence interval (CI): 1.02, 2.34; p = .039) and sexual (aOR = 2.02, 95% CI: 1.10, 3.72; p < .001) IPV were significantly associated with significant depression symptoms. The relationship between physical IPV and significant depression symptoms was not statistically significant (aOR = 0.68, 95% CI: 0.44, 1.05; p = .485). Our study confirms findings from high-income countries of the association between IPV and depressive symptoms among women in South Africa. Routine screening for IPV, including emotional IPV and intervention programs for IPV among women, is needed in South Africa.
Individuals with posttraumatic stress disorder (PTSD) have been found to exhibit emotional regulation difficulties. However, the specific neural mechanisms that underlie these difficulties remain ...understudied. This study aimed to use pupillometry as an index function of parasympathetic nervous system activation, to investigate the mechanisms underlying emotional regulation difficulties in individuals with PTSD.
A total of 87 trauma-exposed mothers (34 with PTSD and 53 non-PTSD controls) completed an eye tracking assessment in which pupillary dilation in response to emotionally valenced stimuli was measured. The participants also completed two self-report measures of emotional regulation, namely the Difficulties in Emotional Regulation Scale and the Emotional Regulations Questionnaire. Linear mixed-effect modelling was used to assess potential group differences.
The PTSD group exhibited increased pupillary dilation to positively valenced stimuli compared to the non-PTSD group. However, no significant associations between the self-report measures and pupillary response to emotionally valenced stimuli were found.
Increased pupillary dilation in PTSD may reflect impaired parasympathetic nervous system processes. The lack of association of these measures with self-reported emotion regulation may suggest reporting biases. Larger studies with more generalised populations are required to consolidate these preliminary findings.
Background
Cohort studies have noted associations between hazardous alcohol use during pregnancy and infant growth outcomes, but many have not controlled for potential psychosocial confounders. To ...assess the unique contribution of hazardous alcohol use, we examined its effect on infant growth outcomes while controlling for maternal psychosocial stressors and hazardous tobacco and drug use in a cohort of 986 pregnant South African women enrolled into the Drakenstein Child Health Study between 2012 and 2015.
Methods
Data on psychosocial stressors and maternal risk behaviors were collected between 28 and 32 weeks of gestation. Participants were categorized as hazardous alcohol users if they obtained moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement Screening Test at this assessment or retrospectively reported drinking at least 2 drinks weekly during any trimester of pregnancy. Infant growth outcomes were recorded at delivery. Multivariable regression models examined correlates of hazardous alcohol use and associations between hazardous alcohol use and birth outcomes.
Results
Overall, 13% of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence (adjusted odds ratio (aOR) = 2.08; 95% confidence interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95% CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After controlling for potential psychosocial confounders, hazardous alcohol use remained associated with lower infant weight‐for‐age (B = −0.35, 95% CI: −0.56, −0.14), height‐for‐age (B = −0.46, 95% CI: −0.76, −0.17), and head‐circumference‐for‐age z‐scores (B = −0.43, 95% CI: −0.69, −0.17).
Conclusions
Interventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol‐related infant growth restrictions. As these growth deficits may lead to neurodevelopmental consequences, it is critical to identify alcohol‐related growth restrictions at birth and link exposed infants to early interventions for neurodevelopment.
We examined the effect of hazardous alcohol use among pregnant South African women on infant growth outcomes. Thirteen percent of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence and hazardous tobacco use were associated with hazardous alcohol use during pregnancy. Hazardous alcohol use predicted lower infant weight, height, and head circumference for age z‐scores. Findings demonstrate that interventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol‐related infant growth restrictions.
HIV infection is known to cause developmental delay, but the effects of HIV exposure without infection during pregnancy on child development are unclear. We compared the neurodevelopmental outcomes ...of HIV-exposed uninfected and HIV-unexposed children during their first 2 years of life.
Pregnant women (>18 years of age) at 20–28 weeks' gestation were enrolled into the Drakenstein Child Health cohort study while attending routine antenatal appointments at one of two peri-urban community-based clinics in Paarl, South Africa. Livebirths born to enrolled women during follow-up were included in the birth cohort. Mothers and infants received antenatal and postnatal HIV testing and antiretroviral therapy per local guidelines. Developmental assessments on the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), were done in a subgroup of infants at 6 months of age, and in the full cohort at 24 months of age, with assessors masked to HIV exposure status. Mean raw scores and the proportions of children categorised as having a delay (scores <–2 SDs from the reference mean) on BSID-III were compared between HIV-exposed uninfected and HIV-unexposed children.
1225 women were enrolled between March 5, 2012, and March 31, 2015. Of 1143 livebirths, 1065 (93%) children were in follow-up at 6 months and 1000 (87%) at 24 months. Two children were diagnosed with HIV infection between birth and 24-month follow-up and were excluded from the analysis. BSID-III assessments were done in 260 (24%) randomly selected children (61 HIV-exposed uninfected, 199 HIV-unexposed) at 6 months and in 732 (73%) children (168 HIV-exposed uninfected, 564 HIV-unexposed) at 24 months. All HIV-exposed uninfected children were exposed to antiretrovirals (88% to maternal triple antiretroviral therapy). BSID-III outcomes did not significantly differ between HIV-exposed uninfected and HIV-unexposed children at 6 months. At 24 months, HIV-exposed uninfected children scored lower than HIV-unexposed for receptive language (adjusted mean difference −1·03 95% CI −1·69 to −0·37) and expressive language (−1·17 –2·09 to −0·24), whereas adjusted differences in cognitive (−0·45 –1·32 to 0·43), fine motor (0·09 –0·49 to 0·66), and gross motor (−0·41 –1·09 to 0·27) domain scores between groups were not significant. Correspondingly, the proportions of HIV-exposed uninfected children with developmental delay were higher than those of HIV-unexposed children for receptive language (adjusted odds ratio 1·96 95% CI 1·09 to 3·52) and expressive language (2·14 1·11 to 4·15).
Uninfected children exposed to maternal HIV infection and antiretroviral therapy have increased odds of receptive and expressive language delays at 2 years of age. Further long-term work is needed to understand developmental outcomes of HIV-exposed uninfected children, especially in regions such as sub-Saharan Africa that have a high prevalence of HIV exposure among children.
Bill & Melinda Gates Foundation, SA Medical Research Council, Wellcome Trust.
Abstract
Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how
in utero
...exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study—the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (
β
= −1.95;
p
= 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.
IntroductionThere is growing awareness that psychosocial risk and resilience factors in early life play a key role in influencing later health. Most work has been done in high-income settings, rather ...than low-income and middle-income countries (LMICs), where the majority of the global childhood population resides. The few studies with well-defined cohorts in LMICs have employed various methods and measures, making comparisons across studies challenging. This presentation describes the methodology for infant and child developmental measures used in the Drakenstein Child Health Study (DCHS), a multidisciplinary longitudinal birth cohort study in South Africa.Methods and analysisWe outline a multilevel approach combining a range of measures including parental reports, behaviour observations, clinician-administered scales and brain imaging. Using this approach, we aim at a longitudinal perspective of developmental, cognitive, socioemotional and neurophysiological outcomes in a birth cohort of children in an LMIC.Ethics and disseminationThe study was approved by the faculty of Health Sciences, Human Research Ethics Committee, University of Cape Town (401/2009), Stellenbosch University (N12/02/0002) and the Western Cape Provincial Health Research committee (2011RP45).DiscussionChildren in the DCHS develop in a context typical of many communities in South Africa and other LMICs. There is a critical need for research in LMICs to elucidate underlying factors that inform risk for, and resilience to, poor developmental outcomes in infants born into high-risk communities. Such work may inform effective intervention strategies appropriate to this context.
Intimate partner violence (IPV) has been linked to poor fetal and infant growth. However, factors underlying this relationship are not well understood, particularly in the postnatal time period. In a ...South African cohort, we investigated (1) associations between IPV in pregnancy and growth at birth as well as postnatal IPV and child growth at 12 months and (2) whether maternal depression, tobacco or alcohol use or infant hospitalizations mediated IPV‐growth relationships. Mothers were enrolled in pregnancy. Maternal IPV was measured during pregnancy and 10 weeks postpartum; depression, alcohol and tobacco use were measured during pregnancy and at 6 months postpartum. Child weight and length were measured at birth and 12 months and converted to z‐scores for analysis. Linear regression and structural equation models investigated interrelationships between IPV and potential mediators of IPV‐growth relationships. At birth, among 1,111 mother–infant pairs, maternal emotional and physical IPV were associated with reduced weight‐for‐age z‐scores (WFAZ). Only physical IPV was associated with length‐for‐age z‐scores (LFAZ) at birth. Antenatal maternal alcohol and tobacco use mediated IPV‐growth relationships at birth. Postnatally, among 783 mother–infant pairs, emotional and physical IPV were associated with reduced WFAZ at 12 months. Only emotional IPV was associated with LFAZ at 12 months. Maternal tobacco use was a mediator postnatally. Findings highlight the role of physical and emotional IPV as risk factors for compromised fetal and infant growth. Findings underscore the importance of programmes to address interrelated risk factors for compromised infant growth, specifically IPV and substance use, which are prevalent in high‐risk settings.
Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality. There is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). ...Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort study. Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0-6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0-6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was associated with increased incidence rates of hospitalisation in infants (IRR 1.63 95% CI 1.29-2.05) and longer hospital admission (p = 0.004). Prematurity (HR 2.82 95% CI 2.28-3.49), delayed infant vaccinations (HR 1.43 95% CI 1.12-1.82), or raised maternal HIV viral load in HEU infants were risk factors for hospitalisation; breastfeeding was protective (HR 0.69 95% CI 0.53-0.90). In conclusion, children in SSA experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at greater risk of hospitalisation in infancy compared to HUU children. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have additional impact in reducing hospitalisation.
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