Neuroendocrine mechanisms in the links between early life stress, affect, and youth substance use: A conceptual model for the study of sex and gender differences.

Early life stress (ELS) is defined as an acute or chronic stressor that negatively impacts a child's development. ELS is associated with substance use and mental health problems. This narrative literature review focuses on sex and gender differences in the effects of ELS on 1) adolescent neuroendocrine development; 2) pubertal brain maturation; and 3) development of internalizing symptoms and subsequent substance use. We posit that ELS may generate larger hormonal dysregulation in females than males during puberty, increasing internalizing symptoms and substance use. Future research should consider sex and gender differences in neuroendocrine developmental processes when studying the link between ELS and negative health outcomes.

Family-Focused Universal Substance Use Prevention in Primary Care: Advancing a Pragmatic National Healthcare Agenda.

This article advances ideas presented at a National Academies of Sciences, Engineering, and Medicine workshop in 2022 that highlighted clinical practice and policy recommendations for delivering universal, family-focused substance use preventive interventions in pediatric primary care. Pediatric primary care is a natural setting in which to offer families universal anticipatory guidance and links to systematic prevention programming; also, several studies have shown that offering effective parenting programs in primary care is feasible. The article describes a blueprint for designing a pragmatic national agenda for universal substance use prevention in primary care that builds on prior work. Blueprint practice schematics leverage efficacious family-focused prevention programs, identify key program implementation challenges and resources, and emphasize adopting a core element approach and utilizing digital interventions. Blueprint policy schematics specify avenues for improving cross-sector policy and resource alignment and collaboration; expanding, diversifying, and strengthening the prevention workforce; and enhancing financing for family-focused prevention approaches. The article then draws from these schematics to assemble a candidate universal prevention toolkit tailored for adolescent patients that contains four interlocking components: education in positive parenting practices, parent and youth education in substance use risks, a parent-youth structured interaction task, and parent and youth linkage to in-person and web-based prevention resources.

Contrasting speed and accuracy approaches to measure executive functions in three low-and middle-income countries.

Executive functions (EF) can be measured by tests assessing accuracy, reaction times and by computing scores which combine these two components. Interpretation issues can arise from the use of different scoring methods across studies. Given that EF measures and their scoring methods are predominantly developed and validated in high income countries, little is known about the generalisability of such methods cross- culturally. The current paper compares two different established scoring approaches for measures of inhibition and cognitive flexibility: difference scores (which utilise reaction time only) and computed scores (combining accuracy and reaction time). We utilised data collected in adulthood from three low- and middle-income birth cohorts (Guatemala, Philippines, South Africa). Non-normal distributions were observed for both scoring methods in all three samples; however, this was more pronounced for the difference score method. Differing distribution patterns were observed across the three cohorts, which was especially evident in the Guatemala cohort, highlighting potential issues with using these methods across diverse populations. The data suggest that the computed scores may be a reliable measure of EF. However, the different ways of scoring and interpreting EF instruments need to be considered carefully for each population before use.

Assessing household financial burdens for preprimary education and associated socioeconomic inequalities: a case study in China.

BACKGROUND: Providing young children with universal access to preprimary education (PPE) is considered a powerful tool for human capital development and eliminating the intergenerational transmission of poverty. To remove household financial barrier for achieving universal PPE, this study proposed a measure to identify households incurring 'heavy financial burdens from paying for PPE' (HBPPE) and conducted a case study in China. METHODS: Using nationally representative data in 2019, we estimated the percentage of households with HBPPE (spent 7% or more of their total annual expenditure) and associated socioeconomic inequalities. We also applied a three-level logit regression model to investigate the factors associated with the probabilities of households incurring HBPPE. RESULTS: Half of the sampled households spent 7% or more of their expenditures on PPE. Households in the lowest wealth quintile (54%) or households with children attending private PPE (55%) had higher percentages of HBPPE than households in other wealth quintiles (eg, 51% in the highest wealth quintile) or households with children attending public kindergartens (41%). Logit regression analysis shows that the poorest households and households with children attending private kindergarten were more likely to incur HBPPE than their counterparts. CONCLUSION: To ensuring universal access to PPE in China, future policy should consider increasing the enrolment of children from low-income families in public kindergartens and increasing governmental investments in low-income households by subsidising children attending PPE.

Growth in Infancy and Childhood and Age at Menarche in Five Low- or Middle-Income Countries: Consortium of Health Orientated Research in Transitional Societies (COHORTS).

BACKGROUND: Earlier age at menarche is associated with behavioral and noncommunicable disease risks. The influence of birth weight (BW) (intrauterine) and postnatal growth on age at menarche is not well studied in low- and middle-income countries (LMICs). OBJECTIVE: Therefore, we investigated these associations in 5 LMIC birth cohorts. METHODS: We analyzed data from Brazil, Guatemala, India, the Philippines, and South Africa (n = 3983). We derived stunting (< -2 SD scores) at 24 mo using the WHO child growth standards. We generated interaction terms with categorized BW and conditional weight (lighter < 0 or heavier ≥ 0), and height (shorter < 0 or taller ≥ 0) z-scores. We categorized early-, modal-, and late-onset menarche and used multilevel ordinal regression. We used multilevel linear regression on continuous age at menarche. RESULTS: Mean age at menarche was 12.8 y (95% CI: 12.7 12.9). BW was not associated with age at menarche. Conditional height at 24 mo and mid-childhood (OR: 1.35; 95% CI: 1.27, 1.44 and 1.32; 1.25, 1.41, respectively) and conditional weight at 24 mo and mid-childhood (OR: 1.15; 1.08, 1.22 and 1.18; 1.11, 1.25, respectively) were associated with increased likelihood of early-onset menarche. Being heavier at birth and taller at 24 mo was associated with a 4-mo (95% CI: 0.8, 7.6) earlier age at menarche than being lighter at birth and shorter at 24 mo. Being heavier at birth but lighter in mid-childhood was associated with a 3-mo (95% CI: 0.8, 4.8) later age at menarche than being lighter at birth and mid-childhood. Age at menarche was 7 mo later in stunted than nonstunted girls. CONCLUSION: Age at menarche is inversely related to relative weight gain but also to rapid linear growth among those born shorter but remained stunted, and those born taller and grew excessively. These findings do not deter the global health goal to reduce growth faltering but emphasize the potential adverse effects of an obesogenic environment on adolescent development.

Childhood adversity during the post-apartheid transition and COVID-19 stress independently predict adult PTSD risk in urban South Africa: A biocultural analysis of the stress sensitization hypothesis.

OBJECTIVES: The COVID-19 pandemic in South Africa introduced new societal adversities and mental health threats in a country where one in three individuals are expected to develop a psychiatric condition sometime in their life. Scientists have suggested that psychosocial stress and trauma during childhood may increase one's vulnerability to the mental health consequences of future stressors-a process known as stress sensitization. This prospective analysis assessed whether childhood adversity experienced among South African children across the first 18 years of life, coinciding with the post-apartheid transition, exacerbates the mental health impacts of psychosocial stress experienced during the 2019 coronavirus (COVID-19) pandemic (ca. 2020-2021). MATERIALS AND METHODS: Data came from 88 adults who participated in a follow-up study of a longitudinal birth cohort study in Soweto, South Africa. Childhood adversity and COVID-19 psychosocial stress were assessed as primary predictors of adult PTSD risk, and an interaction term between childhood adversity and COVID-19 stress was calculated to evaluate the potential effect of stress sensitization. RESULTS: Fifty-six percent of adults exhibited moderate-to-severe PTSD symptoms. Greater childhood adversity and higher COVID-19 psychosocial stress independently predicted worse post-traumatic stress disorder symptoms in adults. Adults who reported greater childhood adversity exhibited non-significantly worse PTSD symptoms from COVID-19 psychosocial stress. DISCUSSION: These results highlight the deleterious mental health effects of both childhood trauma and COVID-19 psychosocial stress in our sample and emphasize the need for greater and more accessible mental health support as the pandemic progresses in South Africa.

Global tracking of access and quality in early childhood care and education.

Investments in early childhood care and education (ECCE) have contributed to a growing demand for internationally comparable data. Yet data on access to quality ECCE are not routinely collected in many countries, leading to limited information on equitable access to ECCE, quality of provision, and the impact on learning and wellbeing outcomes. This paper outlines the current status of global measurement of access to quality ECCE and identifies issues with definitions, availability, and accuracy of ECCE data across countries and outlines paths forward. We argue that estimates of access to ECCE should be based on children's participation in quality ECCE across multiple program types, rather than enrollment or attendance alone, given the critical importance of dosage and participation for ensuring positive benefits from ECCE. Governments, international organizations, and researchers all have roles to play in setting standards to define and monitor ECCE, generating workable tools for measuring nationally, and globally investing in national monitoring systems and routine household surveys to obtain accurate estimates of access to quality ECCE.

Infection, nutritional status, and body composition: Associations at birth and 6 months postnatally in Soweto, South Africa.

INTRODUCTION: The impact of infection on infant nutritional status, body size, and growth is well documented. However, research into the impact of infection on infant body composition is limited. Greater understanding is, therefore, needed on the effects of infection in early life. METHODS: Associations between a composite morbidity index consisting of the sum of the cumulative tallies for a range of symptoms representing infection and morbidity in the infants and nutritional status (height-for-age (HAZ), and weight-for-height (WHZ)), and body composition (fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI)) at 6 months of age were investigated using hierarchical regression analysis. RESULTS: The sample comprised data between birth and 6 months postnatally, of 156 infants who were a priori born healthy in Soweto, South Africa. Morbidity, over the cumulative period of birth to 6 months, was associated with lower FMI (ß = -1.77) and lower FM (ß = -0.61), and conversely with higher FFM (ß = 0.94), in infants at 6 months. No associations were found between the morbidity index and FFMI, HAZ, and WHZ. Increased birthweight was associated with a higher FFM (ß = 0.66), HAZ (ß = 1.14), and WHZ (ß = 0.87). Finally, safely managed sanitation facilities, representative of reduced environmental exposure to fecal-oral transmission pathways were associated with a higher HAZ (ß = 1.21). DISCUSSION: Reduction in FMI and FM and exposure to inflammatory cytokines associated with mounting an immune response could alter phenotypic trajectories during to this period of plasticity. From a public health perspective, these results imply that it is important to intensify efforts to prevent infection in infants in the first 6 months postnatally, and that these efforts should concentrate on access to safely managed sanitation facilities.

Family play, reading, and other stimulation and early childhood development in five low-and-middle-income countries.

This paper used longitudinal data from five studies conducted in Bangladesh, Bhutan, Cambodia, Ethiopia, and Rwanda to examine the links between family stimulation and early childhood development outcomes (N = 4904; Mage = 51.5; 49% girls). Results from random-effects and more conservative child-fixed effects models indicate that across these studies, family stimulation, measured by caregivers' engagement in nine activities (e.g., reading, playing, singing), predicted increments in children's early numeracy, literacy, social-emotional, motor, and executive function skills (standardized associations ranged from 0.05 to 0.11 SD). Study-specific models showed variability in the estimates, with null associations in two out of the five studies. These findings indicate the need for additional research on culturally specific ways in which caregivers may support early development and highlight the importance of promoting family stimulation to catalyze positive developmental trajectories in global contexts. RESEARCH HIGHLIGHTS: Research on the links between family stimulation and early childhood development in low-and-middle-income countries (LMICs) is limited. We used longitudinal data from studies conducted in five LMICs to examine the links between family stimulation and early childhood development outcomes. Results suggest that family stimulation predicted increments in children's numeracy, literacy, social-emotional, motor, and executive function skills. We found variability in the observed estimates, with null associations in two out of the five studies, suggesting the need for additional research in LMICs.

The Mitigating Effects of Protective Parenting on Level of Adolescent Substance Use Risk.

Background: Protective parenting clearly reduces the risk of substance use among young people, but its relationship with cumulative risk for substance use, or the number of risk factors a young person experiences, has not been examined. Objectives: The analysis explores how protective parenting is associated with cumulative risk for adolescent substance use. Methods: A nationally representative online survey of adolescents ages 12-17 (N = 965; 50.8% male; 49.2% female) explored the role of a number of protective parenting variables in predicting substance use risk among adolescents. Parenting behaviors, such as providing warmth, trust, and emotional support; spending time together; communicating about substance use; and monitoring were considered protective. Risk factors included having close friends who use substances, witnessing use, low perceptions of harm, unreliable sources of information about substances, perceived access, and lying to parents. Results: 21.7% of respondents reported 0-1 risk factors, 27.6% reported 2-3 risk factors, and 50.7% reported 4 or more risk factors. Controlling for demographics, a protective parenting composite measure of trust, warmth, and emotional support was associated with decreased risk of reporting 4 or more risk factors (0.45 RRR, p<.05) and spending time together was associated with decreased risk of reporting 2-3 and 4 or more risk factors compared to 0-1 risk factors (0.42 RRR, p<.05; 0.43 RRR, p<.05). Conclusion: These findings highlight the importance of protective parenting in mitigating the cumulative risk for youth substance use. Involving parents in prevention efforts should be a routine component of prevention practice, especially for youth at higher risk.

Protocol for the PLAY Study: a randomised controlled trial of an intervention to improve infant development by encouraging maternal self-efficacy using behavioural feedback.

INTRODUCTION: The early infant caregiving environment is crucial in the formation of parent-child relationships, neurobehavioural development and thus child outcomes. This protocol describes the Play Love And You (PLAY) Study, a phase 1 trial of an intervention designed to promote infant development through encouraging maternal self-efficacy using behavioural feedback, and supportive interventions. METHODS AND ANALYSIS: 210 mother-infant pairs will be recruited at delivery from community clinics in Soweto, South Africa, and individually randomised (1:1) into two groups. The trial will consist of a standard of care arm and an intervention arm. The intervention will start at birth and end at 12 months, and outcome assessments will be made when the infants are 0, 6 and 12 months of age. The intervention will be delivered by community health helpers using an app with resource material, telephone calls, in person visits and behavioural feedback with individualised support. Every 4 months, mothers in the intervention group will receive rapid feedback via the app and in person on their infant's movement behaviours and on their interaction styles with their infant. At recruitment, and again at 4 months, mothers will be screened for mental health risk and women who score in the high-risk category will receive an individual counselling session from a licensed psychologist, followed by referral and continued support as necessary. The primary outcome is efficacy of the intervention in improving maternal self-efficacy, and the secondary outcomes are infant development at 12 months, and feasibility and acceptability of each component of the intervention. ETHICS AND DISSEMINATION: The PLAY Study has received ethical approval from the Human Research Ethics Committee of the University of the Witwatersrand (M220217). Participants will be provided with an information sheet and required to provide written consent prior to being enrolled. Study results will be shared via publication in peer-reviewed journals, conference presentation and media engagement. TRIAL REGISTRATION NUMBER: This trial was registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 10 February 2022 (identifier: PACTR202202747620052).

Growth patterns in childhood and adolescence and adult body composition: a pooled analysis of birth cohort studies from five low and middle-income countries (COHORTS collaboration).

OBJECTIVE: We examined associations among serial measures of linear growth and relative weight with adult body composition. DESIGN: Secondary data analysis of prospective birth cohort studies. SETTINGS: Six birth cohorts from Brazil, Guatemala, India, the Philippines and South Africa. PARTICIPANTS: 4173 individuals followed from birth to ages 22-46 years with complete and valid weight and height at birth, infancy, childhood and adolescence, and body composition in adult life. EXPOSURES: Birth weight and conditional size (standardised residuals of height representing linear growth and of relative weight representing weight increments independent of linear size) in infancy, childhood and adolescence. PRIMARY OUTCOME MEASURES: Body mass index, fat mass index (FMI), fat-free mass index (FFMI), fat mass/fat-free mass ratio (FM/FFM), and waist circumference in young and mid-adulthood. RESULTS: In pooled analyses, a higher birth weight and relative weight gains in infancy, childhood and adolescence were positively associated with all adult outcomes. Relative weight gains in childhood and adolescence were the strongest predictors of adult body composition (ß (95% CI) among men: FMI (childhood: 0.41 (0.26 to 0.55); adolescence: 0.39 (0.27 to 0.50)), FFMI (childhood: 0.50 (0.34 to 0.66); adolescence: 0.43 (0.32 to 0.55)), FM/FFM (childhood: 0.31 (0.16 to 0.47); adolescence: 0.31 (0.19 to 0.43))). Among women, similar patterns were observed, but, effect sizes in adolescence were slightly stronger than in childhood. Conditional height in infancy was positively associated with FMI (men: 0.08 (0.03 to 0.14); women: 0.11 (0.07 to 0.16)). Conditional height in childhood was positively but weakly associated with women's adiposity. Site-specific and sex-stratified analyses showed consistency in the direction of estimates, although there were differences in their magnitude. CONCLUSIONS: Prenatal and postnatal relative weight gains were positive predictors of larger body size and increased adiposity in adulthood. A faster linear growth in infancy was a significant but weak predictor of higher adult adiposity.

Breastfeeding: crucially important, but increasingly challenged in a market-driven world.

In this Series paper, we examine how mother and baby attributes at the individual level interact with breastfeeding determinants at other levels, how these interactions drive breastfeeding outcomes, and what policies and interventions are necessary to achieve optimal breastfeeding. About one in three neonates in low-income and middle-income countries receive prelacteal feeds, and only one in two neonates are put to the breast within the first hour of life. Prelacteal feeds are strongly associated with delayed initiation of breastfeeding. Self-reported insufficient milk continues to be one of the most common reasons for introducing commercial milk formula (CMF) and stopping breastfeeding. Parents and health professionals frequently misinterpret typical, unsettled baby behaviours as signs of milk insufficiency or inadequacy. In our market-driven world and in violation of the WHO International Code for Marketing of Breast-milk Substitutes, the CMF industry exploits concerns of parents about these behaviours with unfounded product claims and advertising messages. A synthesis of reviews between 2016 and 2021 and country-based case studies indicate that breastfeeding practices at a population level can be improved rapidly through multilevel and multicomponent interventions across the socioecological model and settings. Breastfeeding is not the sole responsibility of women and requires collective societal approaches that take gender inequities into consideration.

Marketing of commercial milk formula: a system to capture parents, communities, science, and policy.

Despite proven benefits, less than half of infants and young children globally are breastfed in accordance with the recommendations of WHO. In comparison, commercial milk formula (CMF) sales have increased to about US$55 billion annually, with more infants and young children receiving formula products than ever. This Series paper describes the CMF marketing playbook and its influence on families, health professionals, science, and policy processes, drawing on national survey data, company reports, case studies, methodical scoping reviews, and two multicountry research studies. We report how CMF sales are driven by multifaceted, well resourced marketing strategies that portray CMF products, with little or no supporting evidence, as solutions to common infant health and developmental challenges in ways that systematically undermine breastfeeding. Digital platforms substantially extend the reach and influence of marketing while circumventing the International Code of Marketing of Breast-milk Substitutes. Creating an enabling policy environment for breastfeeding that is free from commercial influence requires greater political commitment, financial investment, CMF industry transparency, and sustained advocacy. A framework convention on the commercial marketing of food products for infants and children is needed to end CMF marketing.

Triple Benefit: Impact of an Integrated Early Childhood Development and PMTCT Intervention on ART Outcomes Among Mothers Living with HIV and Infants in Malawi-An Endline Evaluation.

We conducted a programmatic, observational cohort study with mother-infant pairs (MIPs) enrolled in prevention-of-mother-to-child-transmission (PMTCT) programs in Malawi to assess the feasibility and potential HIV-related benefits of integrating Early Childhood Development (ECD) services into PMTCT programs. Six health facilities were included in the intervention. We offered ECD counseling from the WHO/UNICEF Care for Child Development package in PMTCT waiting spaces while MIPs waited for PMTCT and broader treatment consultations. Primary outcomes were mothers' retention in HIV care at 12 months and infant HIV testing at 6 weeks and 12 months after birth. Routine facility-level data from six comparison health facilities were collected as an adhoc standard of care comparison and used to calculate the cost of delivering the intervention. A total of 607 MIPs were enrolled in the integrated ECD-PMTCT intervention between June 2018 and December 2019. The average age of MIPs was 30 years and 7 weeks respectively. We found that 86% of mothers attended ≥ 5 of the 8 ECD sessions over the course of 12 months; 88% of intervention mothers were retained in PMTCT versus 59% of mothers in comparison health facilities, and 96% of intervention infants were tested for HIV by six weeks compared to 66% of infants in comparison health facilities. Costing data demonstrated the financial feasibility of integrating ECD and PMTCT programs in government health facilities in Malawi. Integrating ECD into PMTCT programs was feasible, acceptable, resulted in better programmatic outcomes for both mothers and infants. Further investigation is required to determine optimal delivery design for scale-up.

Early-life stature, preschool cognitive development, schooling attainment, and cognitive functioning in adulthood: a prospective study in four birth cohorts.

BACKGROUND: Nutrition is important for growth and brain development and therefore cognitive ability. Growth faltering in early childhood, an important indicator of early adversity, is associated with poorer developmental outcomes, some into adulthood, but this association probably reflects early-life deprivation. We aimed to investigate the associations between early-life stature, child IQ, and adult IQ. METHODS: In this cohort study, we used prospective longitudinal data collected in four birth cohorts from Brazil (born in 1993), Guatemala (born in 1969-77), the Philippines (born in 1983-84), and South Africa (born in 1990). Using multivariable linear models, we estimated the relative contributions of early-life stature, child IQ, and schooling (highest school year completed) to adult IQ, including interaction effects among the early-childhood measures and schooling. FINDINGS: We included 2614 individuals in the analysis. Early-life stature was associated with adult IQ (range across eight site-by-sex groups -0·14 to 3·17 IQ points) and schooling (-0·05 to 0·77 years) per height-for-age Z-score. These associations were attenuated when controlling for child IQ (-0·86 to 1·72 for adult IQ and -0·5 to 0·60 for schooling). The association of early-life stature with adult IQ was further attenuated when controlling for schooling (-1·86 to 1·21). Child IQ was associated with adult IQ (range 3·91 to 10·02 points) and schooling (0·25 to 1·30 years) per SD of child IQ in all groups; these associations were unattenuated by the addition of early-life stature to the models. The interaction between schooling and child IQ, but not that between schooling and early-life stature, was positively associated with adult IQ across groups. INTERPRETATION: The observed associations of early-life stature with adult IQ and schooling varied across cohorts and sexes and explained little variance in adult IQ beyond that explained by child IQ. These findings suggest that interventions targeted at growth for health and early development are important. Our results are consistent with the inference that improving long-term cognitive outcomes might require interventions that more specifically target early cognitive ability. FUNDING: Bill & Melinda Gates Foundation.

Maternal Education Potentially Moderates the MAOA uVNTR Effects on Externalizing Behavior in Black South African Children.

Interactions between the MAOA uVNTR and rearing environment are suggested to influence the developmental manifestations of childhood internalizing and externalizing behavior. However, few studies in the MAOA literature have included continental African children, or focused on non-clinical samples. We explored the main and interactive effects of the MAOA uVNTR (high and low activity alleles) in Black South African male (n = 478) and female (n = 540) children who were part of the longitudinal Birth to Twenty Plus cohort. Historical data on birth weight, gestational age at delivery, socioeconomic status, and maternal education were combined with genotypic information and analyzed using regression modeling. We found no significant main effects for the MAOA uVNTR on childhood behavior in either sex. A significant interaction (p = .04) was identified between MAOA and maternal education, suggesting that externalizing behavior in boys carrying a low activity MAOA allele varied in direct proportion to the education levels of their mothers. However, the model fit failed to reach significance, possibly due to our inclusion of only non-clinical pre-pubertal males. No significant interactions were detected for female children. Our findings lend tentative credibility to the Environmental Sensitivity metaframework, which suggests that MAOA is an important plasticity factor in childhood development.

Psychological legacies of intergenerational trauma under South African apartheid: Prenatal stress predicts greater vulnerability to the psychological impacts of future stress exposure during late adolescence and early adulthood in Soweto, South Africa.

BACKGROUND: South Africa's rates of psychiatric morbidity are among the highest in sub-Saharan Africa and are foregrounded by the country's long history of political violence during apartheid. Growing evidence suggests that in utero stress exposure is a potent developmental risk factor for future mental illness risk, yet the extent to which the psychiatric effects of prenatal stress impact the next generation are unknown. We evaluate the intergenerational effects of prenatal stress experienced during apartheid on psychiatric morbidity among children at ages 17-18 and also assess the moderating effects of maternal age, social support, and past household adversity. METHODS: Participants come from Birth-to-Twenty, a longitudinal birth cohort study in Soweto-Johannesburg, South Africa's largest peri-urban township which was the epicentre of violent repression and resistance during the final years of the apartheid regime. Pregnant women were prospectively enrolled in 1990 and completed questionnaires assessing social experiences, and their children's psychiatric morbidity were assessed at ages 17-18. RESULTS: Full data were available from 304 mother-child pairs in 2007-8. Maternal prenatal stress in 1990 was not directly associated greater psychiatric morbidity during at ages 17-18. Maternal age and past household adversity moderated the intergenerational mental health effects of prenatal stress such that children born to younger mothers and late adolescent/young adult children experiencing greater household adversity exhibited worse psychiatric morbidity at ages 17-18. Social support did not buffer against the long-term psychiatric impacts of prenatal stress. CONCLUSIONS: Greater prenatal stress from apartheid predicted adverse psychiatric outcomes among children born to younger mothers and adolescents/young adults who experienced greater concurrent stress. Our findings suggest that prenatal stress may affect adolescent mental health, have stress-sensitising effects, and represent possible intergenerational effects of trauma experienced under apartheid in this sample.