Exposure to Violence and Mental Health Outcomes Among Pre-schoolers in a South African Birth Cohort.

Little is known about the relationship between violence exposure and mental health in preschoolers living in low- and middle-income countries (LMICs). Multiple regression analyses investigated associations between violence exposure and mental health in the Drakenstein Child Health Study (N = 978), a South African birth cohort. Lifetime violence exposure was assessed at age 4.5 years using the parent-report Child Exposure to Community Violence Checklist (CECV). Mental health was assessed at age 5 years using the Child Behaviour Checklist (CBCL 1.5-5). Eighty-three percent of the children were exposed to some form of violence. Internalising and externalising behaviours were positively associated with overall violence exposure (ß per one unit change in the overall score = 0.55 [0.16, 0.94] and ß = 0.53 [0.23, 0.84], respectively), domestic victimisation (ß per one unit change in the subscore = 1.28 [0.28, 2.27]; ß = 1.14 [0.37, 1.90]) and witnessing community violence (ß = 0.77 [0.15, 1.39]; ß = 0.68 [0.19, 1.18]). There was a positive association between polyvictimisation and externalising (ß = 1.02 [0.30, 1.73]) but not internalising (ß = 0.87 [-0.06, 1.80]) behaviour problems. Evidence for an association of witnessing domestic violence with internalising (ß = 0.63 [-0.97, 2.24]) or externalising (ß = 1.23 [-0.04, 2.50]) behaviours was less robust. There was no association between community victimisation and internalising or externalising behaviours (ß = 0.72 [-1.52, 2.97; ß = 0.68 [ -1.06, 2.41]). Observations highlight the risk for mental health problems among preschoolers living in high-violence contexts and emphasize the need for early interventions.

Persistent Impact of Antenatal Maternal Anaemia on Child Brain Structure at 6-7 Years of Age: A South African Child Health Study.

Background: The study aim was to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, putamen, and caudate nucleus volumes previously described in children at age 2-3 years persist to age 6-7 years in the Drakenstein Child Health Study (DCHS). Methods: This neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin<11g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia. Results: Overall, 157 children (Mean [SD] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85% (50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference, -6.77%; p=0.003), left caudate nucleus (adjusted percentage difference, -5.98%, p=0.005), and right caudate nucleus (adjusted percentage difference, -6.12%; p=0.003). Continuous maternal haemoglobin was positively associated with total corpus callosum (ß=0.239 [CI: 0.10 to 0.38]; p<0.001) and caudate nucleus (ß=0.165 [CI: 0.02 to 0.31]; p=0.027) volumes. In a sub-group (n=89) with child haemoglobin data (Mean [SD] age of 76.06[4.84]), the prevalence of antenatal maternal anaemia and postnatal child anaemia was 38.20% (34/89) and 47.19% (42/89), respectively. There was no association between maternal and child anaemia (c2 = 0.799; p=0.372), and child anaemia did not contribute to regional brain volume differences associated with maternal anaemia. Conclusions: Associations between maternal anaemia and regional child brain volumes previously reported at 2-3 years of age were consistent and persisted to 6-7 years of age. Findings support the importance of optimizing antenatal maternal health and reinforce these brain regions as a future research focus on intervention outcomes.

Language outcomes of preschool children who are HIV-exposed uninfected: An analysis of a South African cohort.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.

Efficacy of a dialogic book-sharing intervention in a South African birth cohort: A randomized controlled trial.

OBJECTIVE: Evidence shows that dialogic book-sharing improves language development in young children in low-middle income countries (LMICs), particularly receptive and expressive language. It is unclear whether this intervention also boosts development of other neurocognitive and socio-emotional domains in children. Using a randomized controlled trial (RCT) nested in the Drakenstein Child Health Study (DCHS), a book-sharing intervention was implemented in caregivers of 3.5-year-old preschool children living in low-income South African communities. METHODS: 122 Caregivers and their children (mean age 3.5 years) were randomly assigned to an intervention group (n = 61) or waitlist control group (n = 61). A neurocognitive battery determined baseline receptive and expressive language, executive function, theory of mind, and behavior scores. RESULTS: No differences were observed between intervention and control groups on receptive and expressive language, or any of the neurocognitive or socio-emotional measures from baseline (3.5 years) to 4 months post-intervention administration (4 years). CONCLUSION: The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated at 4 months post-intervention, in children from 3.5 to 4 years of age. This suggests the importance of early intervention and emphasizes the need for further research on adaptation of book-sharing for older participants in a South African context. TRIAL REGISTRATION: retrospectively registered on 03/04/2022 PACTR202204697674974.

1H-MRS neurometabolite profiles and motor development in school-aged children who are HIV-exposed uninfected: a birth cohort study.

Objective: Alterations in regional neurometabolite levels as well as impaired neurodevelopmental outcomes have previously been observed in children who are HIV-exposed uninfected (CHEU). However, little is known about how neurometabolite profiles may relate to their developmental impairment. This study aimed to compare neurometabolite concentrations in school-aged CHEU and children who are HIV-unexposed (CHU) and to explore associations of neurometabolite profiles with functional neurodevelopment in the context of perinatal HIV exposure. Methods: We used 3 T single voxel proton magnetic resonance spectroscopy (1H-MRS) to quantify absolute and relative neurometabolites in the parietal gray and parietal white matter in school-aged CHEU and aged- and community-matched CHU. Functional neurodevelopmental outcomes were assessed using the early learning outcome measure (ELOM) tool at 6 years of age. Results: Our study included 152 school-aged children (50% males), 110 CHEU and 42 CHU, with an average age of 74 months at the neuroimaging visit. In an adjusted multiple linear regression analysis, significantly lower glutamate (Glu) concentrations were found in CHEU as compared to CHU in the parietal gray matter (absolute Glu, p = 0.046; Glu/total creatine (Cr+PCr) ratios, p = 0.035) and lower total choline to creatine ratios (GPC+PCh/Cr+PCr) in the parietal white matter (p = 0.039). Using factor analysis and adjusted logistic regression analysis, a parietal gray matter Glu and myo-inositol (Ins) dominated factor was associated with HIV exposure status in both unadjusted (OR 0.55, 95% CI 0.17-0.45, p = 0.013) and adjusted analyses (OR 0.59, 95% CI 0.35-0.94, p = 0.031). With Ins as one of the dominating metabolites, this neurometabolic factor was similar to that found at the age of two years. Furthermore, this factor was also found to be correlated with ELOM scores of gross motor development in CHEU (Pearson's r = -0.48, p = 0.044). In addition, in CHEU, there was a significant association between Ins/Cr+PCr ratios in the parietal white matter and ELOM scores of fine motor coordination and visual motor integration in CHEU (Pearson's r = 0.51, p = 0.032). Conclusion: Reduced Glu concentrations in the parietal gray matter may suggest regional alterations in excitatory glutamatergic transmission pathways in the context of perinatal HIV and/or antiretroviral therapy (ART) exposure, while reduced Cho ratios in the parietal white matter suggest regional myelin loss. Identified associations between neurometabolite profiles and gross and fine motor developmental outcomes in CHEU are suggestive of a neurometabolic mechanism that may underlie impaired motor neurodevelopmental outcomes observed in CHEU.

Early Childhood Violence Exposure Patterns in The Drakenstein Child Health Study (DCHS).

Background: Research has highlighted high rates of exposure to violence among South African youth. However, work to date has been largely cross-sectional, focused on violence exposure during the adolescence period, and has been limited to specific types of violence exposure. We examined violence exposure in South African preschool children between 3 and 6 years of age, capturing both direct and indirect forms of violence, and tested for potential sex differences across the several types of exposures. Methods: Lifetime direct and indirect exposure to domestic and community violence was measured by parental report when children were 3.5 years (N = 530), 4.5 years (N = 749) and 6 years of age (N= 417) in a South African birth cohort located in a peri-urban community. Results: There are three main findings. First, a large proportion of children (72%-75%) were reported as having been exposed to some form of direct or indirect violent experience in their homes or communities from a young age. Second, there was significant polyvictimization,  with 49% of the children being exposed to more than one type of violence by age 6. Third, by 4.5 years of age, there was evidence that boys were more likely than girls to be exposed to domestic victimisation (28% vs. 17%) and polyvictimization (38% vs. 28%). Conclusions: These findings highlight the high levels of violence exposure in young South African children, particularly among boys, and the need for prevention at both the community and individual levels.

Maternal perinatal depression and child brain structure at 2-3 years in a South African birth cohort study.

Maternal perinatal depression is associated with risk of adverse child developmental outcomes and differences in offspring brain structure. Evidence from low- and middle-income countries is lacking as is an investigation of antenatal, postnatal, and persistent depression in the same sample. In a South African birth cohort, we investigated the effect of antenatal and postpartum maternal depressive symptoms on offspring brain structure at 2-3 years of age. Magnetic resonance imaging was performed, extracting cortical thickness and surface areas in frontal cortex regions of interest and subcortical volumes using FreeSurfer software. Maternal depressive symptoms were measured using the Edinburgh Postpartum Depression Scale and the Beck Depression Inventory II antenatally and at 6-10 weeks, 6 months, 12 months, and 18 months postpartum and analyzed dichotomously and continuously. Linear regressions were used controlling for child age, sex, intracranial volume, maternal education, age, smoking, alcohol use and HIV. 146 children were included with 38 (37%) exposed to depressive symptoms antenatally and 44 (35%) exposed postnatally. Of these, 16 (13%) were exposed to both. Postpartum, but not antenatal, depressive symptoms were associated with smaller amygdala volumes in children (B = -74.73, p = 0.01). Persistent maternal depressive symptoms across pregnancy and postpartum were also independently associated with smaller amygdala volumes (B = -78.61, p = 0.047). Differences in amygdala volumes among children exposed to postnatal as well as persistent maternal depressive symptomatology underscore the importance of identifying women at-risk for depression during the entire perinatal period.

DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort.

BACKGROUND: Exposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother to child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10 µm or less (PM10) was measured inside participants' homes during the second trimester of pregnancy. RESULTS: A total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM10 and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01, 0.86] for cg00694520 to 0.54 [0.11, 1.56] for cg05023582. CONCLUSIONS: Our findings suggest that DNAm may mediate the association between prenatal PM10 exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.

Antenatal maternal intimate partner violence exposure is associated with sex-specific alterations in brain structure among young infants: Evidence from a South African birth cohort.

Maternal psychological distress during pregnancy has been linked to adverse outcomes in children with evidence of sex-specific effects on brain development. Here, we investigated whether in utero exposure to intimate partner violence (IPV), a particularly severe maternal stressor, is associated with brain structure in young infants from a South African birth cohort. Exposure to IPV during pregnancy was measured in 143 mothers at 28-32 weeks' gestation and infants underwent structural and diffusion magnetic resonance imaging (mean age 3 weeks). Subcortical volumetric estimates were compared between IPV-exposed (n = 63; 52% female) and unexposed infants (n = 80; 48% female), with white matter microstructure also examined in a subsample (IPV-exposed, n = 28, 54% female; unexposed infants, n = 42, 40% female). In confound adjusted analyses, maternal IPV exposure was associated with sexually dimorphic effects in brain volumes: IPV exposure predicted a larger caudate nucleus among males but not females, and smaller amygdala among females but not males. Diffusivity alterations within white matter tracts of interest were evident in males, but not females exposed to IPV. Results were robust to the removal of mother-infant pairs with pregnancy complications. Further research is required to understand how these early alterations are linked to the sex-bias in neuropsychiatric outcomes later observed in IPV-exposed children.

Externalizing behavior in preschool children in a South African birth cohort: Predictive pathways in a high-risk context.

Mental health problems often begin in early childhood. However, the associations of various individual and contextual risk factors with mental health in the preschool period are incompletely understood, particularly in low- to middle-income countries (LMICs) where multiple risk factors co-exist. To address this gap, we prospectively followed 981 children in a South African birth cohort, the Drakenstein Child Health Study, assessing pre-and postnatal exposures and risk factors. The predictive value of these factors for child mental health (assessed by the Child Behavior Checklist) was modeled using structural equation modeling. We identified two key pathways to greater externalizing behavior: (1) prenatal exposure to substances (alcohol and smoking) directly predicted increased externalizing behavior (ß = 0.24, p < 0.001); this relationship was partially mediated by an aspect of infant temperament (negative emotionality; ß = 0.05, p = 0.016); (2) lower socioeconomic status and associated maternal prenatal depression predicted more coercive parenting, which in turn predicted increased externalizing behavior (ß = 0.18, p = 0.001). Findings in this high-risk LMIC cohort cohere with research from higher income contexts, and indicate the need to introduce integrated screening and intervention strategies for maternal prenatal substance use and depression, and promoting positive parenting across the preschool period.

Association of Maternal and Child Anemia With Brain Structure in Early Life in South Africa.

Importance: Anemia affects millions of pregnant women and their children worldwide, particularly in low- and middle-income countries. Although anemia in pregnancy is a well-described risk factor for cognitive development, the association with child brain structure is poorly understood. Objective: To explore the association of anemia during pregnancy and postnatal child anemia with brain structure in early life. Design, Setting, and Participants: This neuroimaging nested cohort study was embedded within the Drakenstein Child Health Study (DCHS), a population-based birth cohort in South Africa. Pregnant individuals were enrolled into the DCHS between 2012 and 2015 from 2 clinics in a periurban setting. Mother-child pairs were assessed prospectively; follow-up is ongoing. A subgroup of children had brain magnetic resonance imaging (MRI) at age 2 to 3 years from 2015 to 2018. This study focused on the 147 pairs with structural neuroimaging and available hemoglobin data. Data analyses were conducted in 2021 and 2022. Exposures: Mothers had hemoglobin measurements during pregnancy, and a subgroup of children had hemoglobin measurements during early life. Anemia was classified as hemoglobin levels less than 11 g/dL based on World Health Organization guidelines; children younger than 6 months were classified using local guidelines. Main Outcomes and Measures: Child brain volumes of global, subcortical, and corpus callosum structures were quantified using T1-weighted MRI. Linear regression models were used to analyze the associations between maternal and child anemia with child brain volumes, accounting for potential confounders. Results: Of 147 children (mean [SD] age at MRI, 34 [2] months; 83 [56.5%] male) with high-resolution MRI scans, prevalence of maternal anemia in pregnancy was 31.3% (46 of 147; median [IQR] gestation of measurement: 13 [9-20] weeks). Maternal anemia during pregnancy was significantly associated with smaller volumes of the child caudate bilaterally (adjusted percentage difference, -5.30% [95% CI, -7.01 to -3.59]), putamen (left hemisphere: -4.33% [95% CI, -5.74 to -2.92]), and corpus callosum (-7.75% [95% CI, -11.24 to -4.26]). Furthermore, antenatal maternal hemoglobin levels were also associated with brain volumes in the caudate (left hemisphere: standardized ß = 0.15 [95% CI, 0.02 to 0.28]; right hemisphere: ß = 0.15 [95% CI, 0.02 to 0.27]), putamen left hemisphere (ß = 0.21 [95% CI, 0.07 to 0.35]), and corpus callosum (ß = 0.24 [95% CI, 0.09 to 0.39]). Prevalence of child anemia was 52.5% (42 of 80; median [IQR] age of measurement: 8.0 [2.7 to 14.8] months). Child anemia was not associated with brain volumes, nor did it mediate the association of maternal anemia during pregnancy with brain volumes. Conclusions and Relevance: In this cohort study, anemia in pregnancy was associated with altered child brain structural development. Given the high prevalence of antenatal maternal anemia worldwide, these findings suggest that optimizing interventions during pregnancy may improve child brain outcomes.

Corrigendum: Applicability of a novel attunement instrument and its relationship to parental sensitivity in infants with and without visual impairments.

[This corrects the article DOI: 10.3389/fpsyg.2022.872114.].

Antenatal maternal depression, early life inflammation and neurodevelopment in a South African birth cohort.

BACKGROUND: Antenatal exposure to maternal psychological adversity, including depression, increases the risk of impaired neurodevelopment in children. The underlying biological mechanisms remain unclear, especially in early life during critical windows of development and maturation. This study investigated the association of antenatal maternal depression, maternal and early life inflammatory markers and neurodevelopmental outcomes in children at 2 years of age. METHODS: A subgroup of mothers and their children (n = 255) that were enrolled in a South African birth cohort study, the Drakenstein Child Health Study, were followed from the antenatal period through to 2 years of child age. Maternal depressive symptoms were measured by the Beck Depression Inventory (BDI-II) at 26 weeks gestation. Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were measured in mothers at enrolment and in their children at 6-10 weeks and at 2 years. Neurodevelopment was assessed at 2 years using the Bayley Scales of Infant and Toddler Development III. RESULTS: Antenatal depressive symptoms (present in 25% of the mothers) were significantly associated with higher levels of IL-7 (p = 0.008), IL-8 (p = 0.019) and TNF-α (p = 0.031) in the mothers after correcting for sociodemographic and lifestyle factors. Serum IL-1ß and NGAL levels were significantly elevated over time in children born to mothers with depressive symptoms compared to those without depression, after controlling for maternal and child health and sociodemographic factors. Elevated infant IL-1ß at 6-10 weeks of age partially mediated the association of maternal depressive symptoms with poorer language scores at 2 years. CONCLUSION: Alterations in early life immunity, as reflected by elevated IL-1ß, is a potential pathway through which antenatal maternal depressive symptoms may impact language development in young children.

Influence of Maternal Childhood Trauma on Perinatal Depression, Observed Mother-Infant Interactions, and Child Growth.

INTRODUCTION: Mothers who have experienced childhood trauma may be at increased risk for disruptions in caregiving behavior, with potential consequences for early child development. However, assessments of caregiving behavior tend to be self-reported, which may bias results, and have been limited in lower-resource settings. METHODS: In an overall sample of 256 South African mothers followed across the perinatal period, this longitudinal study used structural equation modeling to test pathways of association between maternal childhood trauma and depressive symptoms on observed mother-infant interactions at 3.5 months and subsequent child growth outcomes at 1 year. RESULTS: On average, mothers with childhood trauma histories tended to show lower rated overall interactions with their infants (B = - 0.16, p = .013), which in turn was associated with reduced child growth at 1 year (B = 0.17, p = .046). When this model was adjusted for maternal age and relative socioeconomic status (SES), maternal SES strongly explained child growth (B = 0.31, p < .001) such that the direct effect of mother-infant interactions was no longer significant. DISCUSSION: For child growth in a lower-resource setting, quality of mother-infant interactions could be a relevant predictor but more strongly explained by maternal SES factors, suggesting a need for broader approaches that not only improve dyadic relationships but also address maternal ecological resources.

Applicability of a Novel Attunement Instrument and Its Relationship to Parental Sensitivity in Infants With and Without Visual Impairments.

This study investigated the applicability of a novel instrument to assess parent-child attunement in free play interactions, in dyads with an infant with and without visual impairments (VI). We here report the findings on the reliability and applicability of the newly developed Attune & Stimulate Mother-Infant 56-items Instrument (A&S M-I) in two separate samples: one with infants with VI (N = 20) and one with typically sighted infants (N = 24). In addition, we assessed the contribution of parental sensitivity to attunement in dyadic interactions. The A&S M-I is an observational comprehensive instrument of behaviors that captures different body parts and their motility (i.e., finger movements, arm waving, and foot kicking), and different senses (i.e., audio, tactile, and visual). The appropriate responding of a parent to the child's signal (i.e., matching and containing) reflects the ability to attune in the dyad as well as parent's ability to stimulate the child to become engaged in the contact or activity. Consistency assessments revealed good reliability for maternal and infant behaviors, acceptable internal consistency and good test-retest reliability. Furthermore, both samples scored significantly above chance level on attunement, suggesting that the instrument captures parent-infant behavioral coordination, and VI was not related to parent-infant attunement. Lastly, a relation between parental sensitivity and attunement was found only in the TS sample. Altogether, these findings provide promising initial evidence of the applicability of the A&S M-I instrument for assessing dyadic attunement across different populations and ages. Having assessed the applicability of this observational instrument, future work should corroborate these findings in larger samples.

In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study.

BACKGROUND AND AIMS: There is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10 µm, PM10) and tobacco smoke with neurodevelopment and 2) to determine whether these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA). METHODS: Data of 734 children from the South African Drakenstein Child Health Study were analyzed. Prenatal PM10 exposure was measured using devices placed in the families' homes. Maternal smoking during pregnancy was determined by maternal urine cotinine measures. The Bayley Scales of Infant and Toddler Development III (BSID-III) was used to measure cognition, language and motor development and adaptive behavior at two years of age. Linear regression models adjusted for maternal age, gestational age, sex of child, ancestry, birth weight/length, and socioeconomic status were used to explore associations between air pollutants and BSID-III scores. A mediation analysis was conducted to analyze if these associations were mediated by ΔGA using DNA methylation measurements from cord blood. RESULTS: An increase of one interquartile range in natural-log transformed PM10 (lnPM10; 1.58 µg/m3) was significantly associated with lower composite scores in cognition, language, and adaptive behavior sub-scores (composite score ß-estimate [95%-confidence interval]: -0.950 [-1.821, -0.120]). Maternal smoking was significantly associated with lower adaptive behavior scores (-3.386 [-5.632, -1.139]). Associations were not significantly mediated by ΔGA (e.g., for PM10 and cognition, proportion mediated [p-value]: 4% [0.52]). CONCLUSION: We found an association of prenatal exposure to indoor air pollution (PM10) and tobacco smoke on neurodevelopment at two years of age, particularly cognition, language, and adaptive behavior. Further research is needed to understand underlying biological mediators.

A Neurometabolic Pattern of Elevated Myo-Inositol in Children Who Are HIV-Exposed and Uninfected: A South African Birth Cohort Study.

Introduction: Exposure to maternal HIV in pregnancy may be a risk factor for impaired child neurodevelopment during the first years of life. Altered neurometabolites have been associated with HIV exposure in older children and may help explain the mechanisms underlying this risk. For the first time, we explored neurometabolic profiles of children who are HIV-exposed and uninfected (CHEU) compared to children who are HIV-unexposed (CHU) at 2-3 years of age. Methods: The South African Drakenstein Child Health Study enrolled women during pregnancy and is following mother-child pairs through childhood. MRI scans were acquired on a sub-group of children at 2-3 years. We used single voxel magnetic resonance spectroscopy to measure brain metabolite ratios to total creatine in the parietal grey matter, and left and right parietal white matter of 83 children (36 CHEU; 47 CHU). Using factor analysis, we explored brain metabolite patterns in predefined parietal voxels in these groups using logistic regression models. Differences in relative concentrations of individual metabolites (n-acetyl-aspartate, myo-inositol, total choline, and glutamate) to total creatine between CHEU and CHU groups were also examined. Results: Factor analysis revealed four different metabolite patterns, each one characterized by covarying ratios of a single metabolite in parietal grey and white matter. The cross-regional pattern dominated by myo-inositol, a marker for glial reactivity and inflammation, was associated with HIV exposure status (OR 1.63; 95% CI 1.11-2.50) which held after adjusting for child age, sex, and maternal alcohol use during pregnancy (OR 1.59; 95% CI 1.07 -2.47). Additionally, higher relative concentrations of myo-inositol to total creatine were found in left and right parietal white matter of CHEU compared to CHU (p=0.025 and p=0.001 respectively). Discussion: Increased ratios of myo-inositol to total creatine in parietal brain regions at age 2-3 years in CHEU are suggestive of early and ongoing neuroinflammatory processes. Altered relative concentrations of neurometabolites were found predominantly in the white matter, which is sensitive to neuroinflammation, and may contribute to developmental risk in this population. Future work on the trajectory of myo-inositol over time in CHEU, alongside markers of neurocognitive development, and the potential for specific neurodevelopmental interventions will be useful.

The Shared Pleasure Paradigm: A study in an observational birth cohort in South Africa.

Mother-infant dyads in low- and middle-income countries (LMICs) may be exposed to a range of factors associated with suboptimal development. Optimal infant development is likely supported by synchronicity in the early mother-infant relationship, but limited corroborative research is available in LMICs. The Drakenstein Child Health Study (DCHS) provided an opportunity to study this synchronicity and its associations in South Africa. A South African birth cohort study investigating early-life determinants of child health in a LMIC context provided participants. The Shared Pleasure (SP) paradigm helped assess early mother-infant synchronicity in videos of a sub-set of 291 mother-infant dyads at their 14-week well baby visit. General linear regression models investigated the relationship between selected maternal and infant characteristics and the presence of Shared Pleasure moments. Out of a possible 291 dyads, 82% (n = 239) yielded Shared Pleasure moments. The mean age of mothers was 27 years, while infant sex distribution comprised 54% females and 46% males. The shortest single Shared Pleasure moment lasted at least 0.5 s and the longest 28 s. Shared Pleasure moments were associated with higher gestation age at delivery (p = 0.008) and higher infant birth weight (p = 0.006), but were not related to mother's mental health and infant health outcomes at 14 weeks. The high frequency of positive Shared Pleasure moments in reciprocal dyadic interactions in this sample suggests that significant disruption in shared pleasure may be present only in extreme cases (e.g. mothers with severe mental disorders). Further work is needed to investigate the mechanisms underlying the associations between early mother-infant synchronicity and better outcomes noted here, and to assess whether SP may serve as a culturally appropriate screen for assessing connectedness.

Maternal emotional and physical intimate partner violence and early child development: investigating mediators in a cross-sectional study in a South African birth cohort.

OBJECTIVES: This study investigated associations between recent maternal intimate partner violence (IPV) (emotional, physical and sexual) and child development at 2 years as well as whether maternal depression or alcohol use mediated these relationships. DESIGN: Cross-sectional study nested in a South African birth cohort. SETTING: Two primary care clinics in Paarl, South Africa. PARTICIPANTS: 626 mother-child pairs; inclusion criteria for maternal antenatal enrolment were clinic attendance and remaining in the study area for at least 1 year; women were excluded if a minor. PRIMARY OUTCOME MEASURES: Child cognitive, language and motor development composite scores. These were assessed using the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Emotional IPV was associated with lower cognitive (ß=-0.32; 95% CI -0.60 to -0.04), language (ß=-0.36; 95% CI -0.69 to -0.01) or motor composite scores (ß=-0.58; 95% CI -0.95 to -0.20) in children at 2 years of age. Physical IPV was associated with lower motor scores (ß=-0.42; 95% CI -0.75 to -0.09) at 2 years. Sexual IPV was unrelated to developmental outcomes, possibly due to low prevalence. Neither recent maternal depression nor alcohol use were shown to mediate the relationship between IPV and developmental outcomes. CONCLUSIONS: Interventions to reduce maternal physical and emotional IPV and early-life interventions for infants and toddlers are needed to promote optimal child development.

Maternal psychosocial risk factors and child gestational epigenetic age in a South African birth cohort study.

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 (ß = -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.