Healthcare provisions associated with multiple HIV-related outcomes among adolescent girls and young women living with HIV in South Africa: a cross-sectional study.

INTRODUCTION: Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV-related outcomes, particularly among AGYW mothers. METHODS: Eligible 12- to 24-year-old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018-2019 (90% recruited). Analysing surveys and medical records from n = 774 participants, we investigated associations of multiple HIV-related outcomes (past-week adherence, consistent clinic attendance, uninterrupted treatment, no tuberculosis [TB] and viral suppression) with seven healthcare provisions: no antiretroviral therapy (ART) stockouts, kind and respectful providers, support groups, short travel time, short waiting time, confidentiality, and safe and affordable facilities. Further, we compared HIV-related outcomes and healthcare provisions between mothers (n = 336) and nulliparous participants (n = 438). Analyses used multivariable regression models, accounting for multiple outcomes. RESULTS: HIV-related outcomes were poor, especially among mothers. In multivariable analyses, two healthcare provisions were "accelerators," associated with multiple improved outcomes, with similar results among mothers. Safe and affordable facilities, and kind and respectful staff were associated with higher predicted probabilities of HIV-related outcomes (p<0.001): past-week adherence (62% when neither accelerator was reported to 87% with both accelerators reported), clinic attendance (71%-89%), uninterrupted ART treatment (57%-85%), no TB symptoms (49%-70%) and viral suppression (60%-77%). CONCLUSIONS: Accessible and adolescent-responsive healthcare is critical to improving HIV-related outcomes, reducing morbidity, mortality and onward HIV transmission among AGYW. Combining these provisions can maximize benefits, especially for AGYW mothers.

Associations of formal childcare use with health and human capital development for adolescent mothers and their children in South Africa: A cross-sectional study.

AIM: This study aims to investigate associations of formal childcare with maternal and child outcomes in a large sample of adolescent mothers. BACKGROUND: Forty percent of adolescent girls in Africa are mothers. Increasing evidence shows positive impacts of formal childcare use for adult women, but no known studies in the Global South examine associations for adolescent mothers and their children. METHODS: We interviewed 1046 adolescent mothers and completed developmental assessments with their children (n = 1139) in South Africa's Eastern Cape between 2017 and 2019. Questionnaires measured childcare use, maternal and child outcomes and socio-demographic background variables. Using cross-sectional data, associations between formal childcare use and outcomes were estimated in multivariate multi-level analyses that accounted for individual-level and family-level clustering. RESULTS: Childcare use was associated with higher odds of being in education or employment (AOR: 4.01, 95% CIs: 2.59-6.21, p < .001), grade promotion (AOR: 2.08, 95% CIs: 1.42-3.05, p < .001) and positive future ideation (AOR: 1.58, 95% CIs: 1.01-2.49, p = .047) but no differences in mental health. Childcare use was also associated with better parenting on all measures: positive parenting (AOR: 1.66, 95% CIs: 1.16-2.38, p = .006), better parental limit-setting (AOR: 2.00, 95% CIs: 1.37-2.93, p < .001) and better positive discipline (AOR: 1.77, 95% CIs: 1.21-2.59, p = .003). For the children, there were no differences in temperament or illness, but a significant interaction showed stronger associations between childcare use and better cognitive, language and motor scores with increasing child age (AOR: 5.04, 95% CIs: 1.59-15.96, p = .006). CONCLUSIONS: Adolescent mothers might benefit substantially from formal childcare, but causal links need to be explored further. Childcare use was also associated with improved parenting and better child development over time, suggesting positive pathways for children. At an average of $9 per month, childcare provisions for adolescent mothers may offer low-cost opportunities to achieve high returns on health and human capital outcomes in Sub-Saharan African contexts.

Measuring Violence Against Children: A COSMIN Systematic Review of the Psychometric and Administrative Properties of Adult Retrospective Self-report Instruments on Child Abuse and Neglect.

Valid, meaningful, and reliable adult retrospective measures of violence against children (VAC) are essential for establishing the prevalence, risk factors, and long-term effects of VAC. We aim to summarize the available evidence on the psychometric properties of adult retrospective VAC measures and to provide evidence-based recommendations for appropriate measure selection. We searched six electronic databases and gray literature for studies that report on the development, content validity, or psychometric properties of adult retrospective child abuse and neglect measures for this review (PROSPERO: CRD4201706). We used the 2018 Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria to evaluate each included study and measure. We assessed if measures included questions on frequency or severity, the perpetrator, or the location of the violence, and noted the administrative practicalities for each instrument such as length, readability, available translations, and cost to access. We identified 288 studies and 77 measures. The quality of evidence ranged from "low" to "high," depending on the measure and the psychometric properties assessed. The measures with the most robust evidence available across multiple contexts are the: ACE and ACE-IQ; FBQ and FBQ-U; CTQ and CTQ-SF; and ICAST-R. This review shows the strengths and weaknesses of retrospective VAC measures. The substantial evidence presented in this review can be used by researchers to make psychometrically sound decisions for measurement selection which should be supported by extensive piloting and adaptation to the respective local context.

Associations of social media and health content use with sexual risk behaviours among adolescents in South Africa.

Increasing rates of mobile phone access present potential new opportunities and risks for adolescents' sexual and reproductive health in resource-poor settings. We investigated associations between mobile phone access/use and sexual risks in a cohort of 10-24-year-olds in South Africa. 1563 adolescents (69% living with HIV) were interviewed in three waves between 2014 and 2018. We assessed mobile phone access and use to search for health content and social media. Self-reported sexual risks included: sex after substance use, unprotected sex, multiple sexual partnerships and inequitable sexual partnerships in the past 12 months. We examined associations between mobile phone access/use and sexual risks using covariate-adjusted mixed-effects logistic regression models. Mobile phone access alone was not associated with any sexual risks. Social media use alone (vs. no mobile phone access) was associated with a significantly increased probability of unprotected sex (adjusted average marginal effects [AMEs] + 4.7 percentage points [ppts], 95% CI 1.6-7.8). However, health content use (vs. no mobile phone access) was associated with significantly decreased probabilities of sex after substance use (AMEs -5.3 ppts, 95% CI -7.4 to -3.2) and unprotected sex (AMEs -7.5 ppts, 95% CI -10.6 to -4.4). Moreover, mobile phone access and health content use were associated with increased risks of multiple sexual partnerships in boys. Health content use was associated with increased risks of inequitable sexual partnerships in adolescents not living with HIV. Results suggest an urgent need for strategies to harness mobile phone use for protection from growing risks due to social media exposure.

Key normative, legal, and policy considerations for supporting pregnant and postpartum adolescents in high HIV-burden settings: a critical analysis.

Rates of adolescent pregnancy within sub-Saharan Africa are increasing. Adolescent mothers ages 10-19 years face a distinct set of risks to their own and their children's health, compounded by many economic, social, and epidemiological challenges, such as living with HIV. In navigating this complex developmental period, many adolescent mothers face structural barriers impeding safe transitions to adulthood and motherhood. Drawing on existing literature and emerging data, we outline three normative, legal, and policy issues - violence and gender inequity, access to sexual and reproductive health services, and access to social and structural supports - which affect the health, wellbeing and development of adolescent mothers and their children. We also highlight emergent evidence about programming and policy changes that can better support adolescent mothers and their children. These key proposed responses include removing barriers to SRH and HIV service integration; ensuring implementation of return-to-school policies; and extending social protection systems to cater for adolescent mothers. Despite ongoing global crises and shifts in funding priorities, these normative, legal, and policy considerations remain critical to safeguard the health and wellbeing of adolescent mothers and their children.

Improving educational and reproductive outcomes for adolescent mothers in South Africa: A cross-sectional analysis towards realising policy goals.

Adolescent mothers face numerous challenges. This study aimed to address the operationalisation of the new South African national policy for young mothers by testing the associations of potential protective provisions with three policy goals: School return, grade promotion, and pregnancy/HIV prevention. Adolescent mothers aged 12-24 from rural and urban communities of South Africa's Eastern Cape completed study questionnaires between 2017-2019. Using multivariate multi-level analysis, we simultaneously estimated associations between hypothesized provisions and protective variables and all policy-aligned goals. School return was associated with using formal childcare services, higher confidence and self-efficacy scores, and remaining in school throughout pregnancy. Grade promotion was associated with greater exposure to friendly and respectful health staff, using formal childcare services, higher confidence and self-efficacy scores, and remaining in school throughout pregnancy. Pregnancy/HIV prevention (condom use) was moderately associated with greater exposure to friendly and respectful health staff. There was evidence of synergies of provisions whereby a combination of protective characteristics showed larger positive effects than receipt of any single factor alone. This study provides essential evidence for operationalising South Africa's new policy on the Prevention and Management of Learner Pregnancy in Schools, and points to implementation strategies that provide low-cost opportunities to promote educational and health outcomes for adolescent mothers.

Effects over time of parenting interventions to reduce physical and emotional violence against children: a systematic review and meta-analysis.

Background: Violence against children affects over one billion children globally. International organisations promote parenting interventions as a main strategy to reduce violence against children. Parenting interventions have therefore been implemented rapidly across the globe. Yet, evidence for their longer-term effects remains unclear. We integrated global evidence to estimate effects over time of parenting interventions to reduce physical and emotional violence against children. Methods: In this systematic review and meta-analysis, we searched 26 databases and trial registries (14 non-English: Spanish, Chinese, Farsi, Russian, Thai) and conducted an extensive grey literature search up to August 01, 2022. We included randomised controlled trials (RCTs) of parenting interventions based on social learning theory for parents of children aged 2-10 years, without time or context restrictions. We critically appraised studies using Cochrane's Risk of Bias Tool. Data were synthesised using robust variance estimation meta-analyses. This study is registered with PROSPERO, CRD42019141844. Findings: We screened 44,411 records and included 346 RCTs. Sixty RCTs reported outcomes on physical or emotional violence. Trials were distributed across 22 countries (22% LMICs). Risk of bias was high for various domains. Outcome data ranged from 0 weeks to 2 years after the intervention, and was largely based on parent self-report. Parenting interventions reduced physical and emotional violent parenting behaviours immediately after the intervention (n = 42, k = 59; d = -0.46; 95% CI: -0.59, -0.33), at 1-6 months follow-up (n = 18, k = 31; d = -0.24; 95% CI: -0.37, -0.11) and at 7-24 months follow-up (n = 12, k = 19; d = -0.18; 95% CI: -0.34, -0.02), but effects were smaller over time. Interpretation: Our findings suggest that parenting interventions can reduce physical and emotional violence against children. Effects are maintained up to 24 months follow-up, but with diminished effect sizes. With global policy interest and imminent importance, research beyond 2 years and how effects can be better sustained over time is urgently needed. Funding: Student scholarship from the Economic Social Research Council, Clarendon, and Wolfson Isaiah Berlin Fund.

Who goes back to school after birth? Factors associated with postpartum school return among adolescent mothers in the Eastern Cape, South Africa.

Early motherhood can negatively impact health, educational, and socio-economic outcomes for adolescent mothers and their children. Supporting adolescent mothers' educational attainment, and timely return to school, may be key to interrupting intergenerational cycles of adversity. Yet, there remains a paucity of evidence on the factors that are associated with mothers' postpartum return to school and the mediators of this process, particularly across sub-Saharan Africa where adolescent pregnancy rates remain high . This paper is based on interviews with 1,046 adolescent mothers from South Africa. Mothers who had returned to school after birth showed lower poverty, fewer repeated grades preceding the pregnancy, continued schooling during pregnancy, higher daycare/crèche use, more family childcare support, and lower engagement in exclusive breastfeeding within six months postpartum. Mediation analyses showed that lower poverty was directly associated with school return and via two indirect pathways: continued schooling during pregnancy and using daycare/crèche services. This study demonstrates that lacking childcare constitutes a major hurdle to mothers' school return which needs to be addressed in addition to socioeconomic and individual-level barriers. Policy makers and practitioners should consider supporting young mothers with combination interventions which include services supporting school retention during pregnancy and access to, and financial supplements for, daycare.

Measuring Violence Against Children: A COSMIN Systematic Review of the Psychometric Properties of Child and Adolescent Self-Report Measures.

Research on violence against children (VAC) requires meaningful, valid, and reliable self-report by children. Many instruments have been used globally and decisions to select suitable measures are complex. This review identifies child and adolescent self-report measures that are most likely to yield valid, reliable, and comparable data in this field. A systematic review (PROSPERO: CRD4201706) was conducted using the 2018 Consensus-based Standards for the selection of health Measurement Instrument (COSMIN) criteria. Six electronic databases and gray literature were searched. Manuscripts published in English and describing the development and psychometric qualities of child/adolescent self-report instruments were included. Thirty-nine original instruments and 13 adaptations were identified in 124 studies. The quality of evidence ranged from "very low" to "high" depending on the measure and the psychometric properties assessed. Most measures were not widely used, and some have been applied in many settings despite limited evidence of their psychometric rigor. Few studies assessed content validity, particularly with children. The ACE, CTQ, CTS-PC, CECA, ICAST, and JVQ have the best psychometric properties. An overview of items measuring frequency, onset, duration, perpetrators, and locations is provided as well as an assessment of the practicalities for administration to help researchers select the instrument best suited for their research questions. This comprehensive review shows the strengths and weaknesses of VAC research instruments. Six measures that have sufficient psychometric properties are recommended for use in research, with the caveat that extensive piloting is carried out to ensure sufficient content validity for the local context and population.

Exploring the cognitive development of children born to adolescent mothers in South Africa.

This study explores the cognitive development of children born to adolescent mothers within South Africa compared to existing reference data, and explores development by child age bands to examine relative levels of development. Cross-sectional analyses present data from 954 adolescents (10-19 years) and their first-born children (0-68 months). All adolescents completed questionnaires relating to themselves and their children, and standardized child cognitive assessments (Mullen Scales of Early Learning) were undertaken. Cognitive development scores of the sample were lower than USA reference population scores and relative performance compared to the reference population was found to decline with increasing child age. When compared to children born to adult mothers in the sub-Saharan African region, children born to adolescent mothers (human immunodeficiency virus [HIV] unexposed; n = 724) were found to have lower cognitive development scores. Findings identify critical periods of development where intervention may be required to bolster outcomes for children born to adolescent mothers. Highlights: An exploration of the cognitive development of children born to adolescent mothers within South Africa utilizing the Mullen Scales of Early Learning.Cognitive development scores of children born to adolescent mothers within South Africa were lower compared to USA norm reference data and declined with child age.Previous studies utilizing the Mullen Scales of Early Learning within sub-Saharan Africa were summarized, and comparisons were made with the current sample.Findings highlight a potential risk of developmental delay among children born to adolescent mothers compared to children of adult mothers in the sub-Saharan African region.

Achieving the health and well-being Sustainable Development Goals among adolescent mothers and their children in South Africa: Cross-sectional analyses of a community-based mixed HIV-status cohort.

The Sustainable Development Goals (SDGs) are a visionary and multi-sectoral agenda for human development. With less than a decade left to reach these targets, it is important to identify those at greatest risk of not meeting these ambitious targets. Adolescent mothers and their children are a highly vulnerable group. We mapped 35 SGD-related targets among 1,046 adolescent mothers and their oldest child (n = 1046). Questionnaires using validated scales were completed by 10- to 24-year-old adolescent girls and young women who had their first child before age 20 in an HIV-endemic district in the Eastern Cape province of South Africa. Maternal outcomes included 26 SDG-aligned indicators, while child-related outcomes included 9 indicators. Data was collected by trained researchers, following informed voluntary consent by the adolescent mothers and their caregivers. Frequencies and chi-square tests were conducted to compare progress along SDG-aligned indicators among adolescent mothers by HIV status. Overall, adolescent mothers reported low attainment of SDG-aligned indicators. While four in five adolescent mothers lived in poor households, nearly 93% accessed at least one social cash transfer and 80% accessed a child support grant for their children. Food security rates among adolescent mothers (71%) were lower than among their children (91%). Only two-thirds of adolescent mothers returned to school after childbirth, and only one-fifth were either studying or employed. Over half of adolescent mothers had experienced at least one type of violence (domestic, sexual or community). HIV-positive status was associated with higher rates of hunger and substance use, poorer school attendance, and higher rates of exposure to violence. Understanding progress and gaps in meeting the SDGs among highly vulnerable groups is critical, particularly for adolescent mothers and their children. These complex vulnerabilities suggest that programming for adolescent mothers must address their unique needs.

The development of children born to young mothers with no, first- or second-generation HIV acquisition in the Eastern Cape province, South Africa: a cross-sectional study.

BACKGROUND: The intergenerational effects of HIV require long-term investigation. We compared developmental outcomes of different generations impacted by HIV-children of mothers not living with HIV, the 'second generation' (ie, with recently infected mothers) and the 'third generation' (ie, children of perinatally infected mothers). METHODS: A cross-sectional community sample of N=1015 young mothers (12-25 years) and their first children (2-68 months, 48.2% female), from South Africa's Eastern Cape Province. 71.3% (n=724) of children were born to mothers not living with HIV; 2.7% (n=27; 1 living with HIV) were third-generation and 26.0% (n=264; 11 living with HIV) second-generation children. Child scores on the Mullen Scales of Early Learning (MSEL), the WHO Ten Questions Screen for Disability and maternal demographics were compared between groups using χ2 tests and univariate approach, analysis of variance analysis. Hierarchical linear regressions investigated predictive effects of familial HIV infection patterns on child MSEL composite scores, controlling for demographic and family environment variables. RESULTS: Second-generation children performed poorer on gross (M=47.0, SD=13.1) and fine motor functioning (M=41.4, SD=15.2) and the MSEL composite score (M=90.6, SD=23.0) than children with non-infected mothers (gross motor: M=50.4, SD=12.3; fine motor: M=44.4, SD=14.1; composite score: M=94.1, SD=20.7). The third generation performed at similar levels to non-exposed children (gross motor: M=52.4, SD=16.1; fine motor: M=44.3, SD=16.1, composite score: M=94.7, SD=22.2), though analyses were underpowered for definite conclusions. Hierarchical regression analyses suggest marginal predictive effects of being second-generation child compared with having a mother not living with HIV (B=-3.3, 95% CI=-6.8 to 0 .1) on MSEL total scores, and non-significant predictive effects of being a third-generation child (B=1.1, 5% CI=-7.5 to 9.7) when controlling for covariates. No group differences were found for disability rates (26.9% third generation, 27.7% second generation, 26.2% non-exposed; χ2=0.02, p=0.90). CONCLUSION: Recently infected mothers and their children may struggle due to the disruptiveness of new HIV diagnoses and incomplete access to care/support during pregnancy and early motherhood. Long-standing familial HIV infection may facilitate care pathways and coping, explaining similar cognitive development among not exposed and third-generation children. Targeted intervention and fast-tracking into services may improve maternal mental health and socioeconomic support.

Adolescent mothers and their children affected by HIV-An exploration of maternal mental health, and child cognitive development.

BACKGROUND: Some children born to adolescent mothers may have developmental challenges, while others do not. Research focusing on which children of adolescent mothers are at the highest risk for cognitive delay is still required. Both maternal HIV status and maternal mental health may affect child development. An examination of maternal mental health, especially in the presence of maternal HIV infection may be timely. This study explores the relationship between the mental health of adolescent mothers (comparing those living with and not living with HIV) and the cognitive development performance scores of their children. Additional possible risk and protective factors for poor child development are explored to identify those children born to adolescent mothers who may be at the greatest risk of poor cognitive development. METHODS: Cross-sectional data utilised within the analyses was drawn from a large cohort of adolescent mothers and their children residing in South Africa. Detailed study questionnaires were completed by adolescent mothers relating to their self and their child and, standardised cognitive assessments were completed by trained researchers for all children using in the Mullen Scales of Early Learning. Chi-square, t-tests (Kruskal Wallis tests, where appropriate), and ANOVA were used to explore sample characteristics and child cognitive development scores by maternal mental health status (operationalised as likely common mental disorder) and combined maternal mental health and HIV status. Multivariable linear regression models were used to explore the relationship between possible risk factors (including poor maternal mental health and HIV) and, child cognitive development scores. RESULTS: The study included 954 adolescent mothers; 24.1% (230/954) were living with HIV, 12.6% (120/954) were classified as experiencing likely common mental disorder. After adjusting for covariates, maternal HIV was found to be associated with reduced child gross motor scores (B = -2.90 [95%CI: -5.35, -0.44], p = 0.02), however, no other associations were identified between maternal likely common mental disorder, or maternal HIV status (including interaction terms), and child cognitive development scores. Sensitivity analyses exploring individual maternal mental health scales identified higher posttraumatic stress symptomology scores as being associated with lower child cognitive development scores. Sensitivity analyses exploring potential risk and protective factors for child cognitive development also identified increased maternal educational attainment as being protective of child development scores, and increased child age as a risk factor for lower development scores. CONCLUSIONS: This study addresses a critical evidence gap relating to the understanding of possible risk factors for the cognitive development of children born to adolescent mothers affected by HIV. This group of mothers experience a complex combination of risk factors, including HIV, likely common mental disorder, and structural challenges such as educational interruption. Targeting interventions to support the cognitive development of children of adolescent mothers most at risk may be of benefit. Clearly a basket of interventions needs to be considered, such as the integration of mental health provision within existing services, identifying multiple syndemics of risk, and addressing educational and structural challenges, all of which may boost positive outcomes for both the mother and the child.

Risk factors for poor mental health among adolescent mothers in South Africa.

In South Africa, high rates of adolescent pregnancy and HIV pose prominent public health challenges with potential implications for mental wellbeing. It is important to understand risk factors for mental health difficulties among adolescent mothers affected by HIV. This study aims to identify the prevalence of likely common mental disorder among adolescent mothers (both living with and not living with HIV) and explores hypothesised risk factors for likely common mental disorder. Cross-sectional data from adolescent mothers (10-19 years; n=1002) utilised within these analyses are drawn from a cohort of young mothers residing in the Eastern Cape Province, South Africa. All mothers completed a detailed questionnaire consisting of standardised measures of sociodemographic characteristics, mental health, and hypothesised risk factors. Logistic regression models were utilised to explore associations between hypothesised risk factors and likely common mental disorder. Risk factors were clustered within a hypothesised socioecological framework and entered into models using a stepwise sequential approach. Interaction effects with maternal HIV status were additionally explored. The prevalence of likely common mental disorder among adolescent mothers was 12.6%. Adolescent mothers living with HIV were more likely to report likely common mental disorder compared to adolescent mothers not living with HIV (16.2% vs 11.2%, X2=4.41, p=0.04). Factors associated with likely common mental disorder were any abuse exposure (OR=2.54 [95%CI:1.20-5.40], p=0.01), a lack of perceived social support (OR=4.09 [95%CI:2.48-6.74], p=<0.0001), and community violence exposure (OR=2.09 [95%CI:1.33-3.27], p=0.001). There was limited evidence of interaction effects between risk factors, and maternal HIV status. Violence exposure and a lack of perceived support are major risk factors for poor mental health among adolescent mothers in South Africa. Violence prevention interventions and social support may help to reduce risk. Identified risk factors spanning individual, interpersonal, and community levels have the potential to impact adolescent maternal mental health.

Which factors affect postpartum educational enrollment of adolescent mothers in South Africa? A latent class analysis.

Interrupted education of adolescent mothers remains a major concern, but limited evidence-based programming exists to support postpartum schooling of this group. This study aimed to better understand the factors that render some adolescent mothers vulnerable to school non-enrollment, and how to reduce these risks. Data from 1,046 adolescent and young mothers (10-24 years) from rural and urban communities in South Africa's Eastern Cape was obtained through a questionnaire containing validated and study-specific measures relating to sociodemographic characteristics, schooling, relationships, violence exposure, and health. Using latent class analysis, we explored emerging latent groups and their relationship to mothers' enrollment in school, college, or tertiary education. The analyses revealed three distinct groups of mothers: The 'most disadvantaged' subgroup (39%) experienced multiple risks, including food insecurity, living in informal housing, lacking positive relationships with their caregiver, and the highest distance to school; The 'disadvantaged' subgroup (44%) did not experience food insecurity whilst reporting better caregiver relationships and lower distance to school. However, this group still showed high probabilities of residing in informal housing and in communities that expose them to violence; A 'least disadvantaged' subgroup (17%) was largely unaffected by economic and community risks and experienced good caregiver relationships. Compared to the most disadvantaged mothers, the least disadvantaged mothers showed the highest probability of being enrolled in education (65% versus 45%). Adolescent motherhood can impede continued enrollment in education and individual-centered interventions alone might not be sufficient to mitigate the risks for non-enrollment. Services and provisions that address severe poverty and improve family relationships might provide an opportunity to positively influence schooling among adolescent mothers.

Adolescent parenthood and HIV-infection in South Africa-Associations with child cognitive development.

HIV, both directly and indirectly, impacts child development outcomes. The most severe impacts are for children infected with HIV, and those exposed but uninfected are also shown to have challenges-though less severe. However, little is known regarding the development of children born to adolescent mothers affected by HIV. This study aims to examine cognitive development for children born to adolescent mothers, comparing those children living with HIV, those HIV exposed and uninfected (HEU) and those HIV unexposed (HU). Analyses utilise cross-sectional data from 920 adolescent mother (10-19 years)-first born child dyads residing in the Eastern Cape Province, South Africa. Participants completed detailed study questionnaires inclusive of validated and study specific measures relating to sociodemographic characteristics, HIV, and maternal and child health. Trained assessors administered standardised child development assessments (using the Mullen Scales of Early Learning) with all children. Chi-square tests and ANOVA tests were used to explore maternal and child characteristics according to child HIV status (HIV, HEU, HU) on cognitive development. Linear regression models were used to explore the cross-sectional associations between child HIV status and child cognitive development. 1.2% of children were living with HIV, 20.5% were classified as being HEU and, 78.3% were classified as HU. Overall, children living with HIV were found to perform lower across developmental domains compared to both HEU and HU groups (composite score of early learning: 73.0 vs 91.2 vs. 94.1, respectively: F = 6.45, p = 0.001). HEU children on average scored lower on all developmental domains compared to HU children, reaching significance on the gross motor domain (p<0.05). Exploratory analyses identified maternal education interruption as a potential risk factor for lower child cognitive development scores and, higher maternal age to be protective of child cognitive development scores. These exploratory findings address a critical evidence gap regarding the cognitive development of children born to adolescent mothers affected by HIV in South Africa. Analyses identify stepwise differences in the average scoring on child cognitive development domains according to child HIV status among children born to adolescent mothers affected by HIV; with children living with HIV performing worse overall. Young mothers and their children may benefit from adapted interventions aimed at bolstering child development outcomes. Targeted programming particularly among younger adolescent mothers and those experiencing education interruption may identify those families, particularly in need. Attention to maternal continuity of education and age of conception may be interventions to consider.

Drifting codes within a stable coding scheme for working memory.

Working memory (WM) is important to maintain information over short time periods to provide some stability in a constantly changing environment. However, brain activity is inherently dynamic, raising a challenge for maintaining stable mental states. To investigate the relationship between WM stability and neural dynamics, we used electroencephalography to measure the neural response to impulse stimuli during a WM delay. Multivariate pattern analysis revealed representations were both stable and dynamic: there was a clear difference in neural states between time-specific impulse responses, reflecting dynamic changes, yet the coding scheme for memorised orientations was stable. This suggests that a stable subcomponent in WM enables stable maintenance within a dynamic system. A stable coding scheme simplifies readout for WM-guided behaviour, whereas the low-dimensional dynamic component could provide additional temporal information. Despite having a stable subspace, WM is clearly not perfect-memory performance still degrades over time. Indeed, we find that even within the stable coding scheme, memories drift during maintenance. When averaged across trials, such drift contributes to the width of the error distribution.

Valproate for acute mania.

BACKGROUND: Bipolar disorder is a severe and common mental disorder where patients experience recurrent symptoms of elevated or irritable mood, depression, or a combination of both. Treatment is usually with psychiatric medication, including mood stabilisers, antidepressants and antipsychotics. Valproate is an effective maintenance treatment for bipolar disorder. However, evidence assessing the efficacy of valproate in the treatment of acute mania is less robust, especially when comparing it to some of the newer antipsychotic agents. This review is an update of a previous Cochrane Review (last published 2003) on the role of valproate in acute mania. OBJECTIVES: To assess the efficacy and tolerability of valproate for acute manic episodes in bipolar disorder compared to placebo, alternative pharmacological treatments, or a combination pharmacological treatments, as measured by the treatment of symptoms on specific rating scales for individual episodes in paediatric, adolescent and adult populations. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. We had also conducted an earlier search of these databases in the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all years to 6 June 2016). We also searched the World Health Organization (WHO) trials portal (ICTRP) and clinicaltrials.gov in September 2018, to identify any additional unpublished or ongoing studies. SELECTION CRITERIA: Single- and double-blind, randomised controlled trials comparing valproate with placebo, alternative antimanic treatments, or a combination of pharmacological treatments. We also considered studies where valproate was used as an adjunctive treatment in combination with another agent separately from studies where it was used in monotherapy. We included male and female patients of all ages and ethnicity with bipolar disorder. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and methodological quality assessment. For analysis, we used the odds ratio (OR) for binary efficacy outcomes and the mean difference (MD) or standardised mean difference (SMD) for continuously distributed outcomes. MAIN RESULTS: Twenty-five trials (3252 participants) compared valproate with either placebo or alternative antimanic treatments to alleviate the symptoms of acute mania. For efficacy, our primary outcome was response rate. For tolerability, our primary outcome was the number of participants with any adverse effect. This meta-analysis included studies focusing on children, adolescents, as well as adults with a range of severity of manic symptoms. The majority of studies focused on adult men and women (aged 18 and above), were conducted in inpatient settings and completed in the US. Five studies in this review focused on children and adolescents (aged 18 and under) so that the review covers an age range from 3 - 82 years. Seven studies contained outpatient participants in some form. Nine studies included data that has been collected outside the US, namely Iran (4 studies), India (3 studies), China (1 study), or across several international countries (1 study).In adults, high-quality evidence found that valproate induces a slightly higher response compared to placebo (45% vs 29%, OR 2.05, 95% CI 1.32 to 3.20; 4 studies, 869 participants). Moderate-quality evidence found there was probably little or no difference in response rates between valproate and lithium (56% vs 62%, OR 0.80, 95% CI 0.48 to 1.35; 3 studies, 356 participants). In adults, low-quality evidence found there may be little or no difference in response rate between valproate and olanzapine (38% vs 44%, OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 667 participants).In the children and adolescent population, the evidence regarding any difference in response rates between valproate and placebo was uncertain (23% vs 22%, OR 1.11, 95% CI 0.51 to 2.38; 1 study, 151 participants, very low-quality evidence). Low-quality evidence found that the response rate of participants receiving valproate may be lower compared to risperidone (23% vs 66%, OR 0.16, 95% CI 0.08 to 0.29; 1 study, 197 participants). The evidence regarding any difference in response rates between valproate and lithium was uncertain (23% vs 34%, OR 0.57, 95% CI 0.31 to 1.07; 1 study, 197 participants, very low-quality evidence).In terms of tolerability in adults, moderate-quality evidence found that there are probably more participants receiving valproate who experienced any adverse events compared to placebo (83% vs 75%, OR 1.63, 95% CI 1.13 to 2.36; 3 studies, 745 participants). Low-quality evidence found there may be little or no difference in tolerability between valproate and lithium (78% vs 86%, OR 0.61, 95% CI 0.25 to 1.50; 2 studies, 164 participants). We did not obtain primary tolerability outcome data on the olanzapine comparison.Within the children and adolescent population, the evidence regarding any difference between valproate or placebo was uncertain (67% vs 60%, OR 1.39, 95% CI 0.71 to 2.71; 1 study, 150 participants, very low-quality evidence). We did not obtain primary tolerability outcome data on the lithium or risperidone comparisons. AUTHORS' CONCLUSIONS: There is evidence that valproate is an efficacious treatment for acute mania in adults when compared to placebo. By contrast, there is no evidence of a difference in efficacy between valproate and placebo for children and adolescents. Valproate may be less efficacious than olanzapine in adults, and may also be inferior to risperidone as a monotherapy treatment for paediatric mania. Generally, there is uncertain evidence regarding whether valproate causes more or less side effects than the other main antimanic therapies. However, evidence suggests that valproate causes less weight gain and sedation than olanzapine.

Dynamic hidden states underlying working-memory-guided behavior.

Recent theoretical models propose that working memory is mediated by rapid transitions in 'activity-silent' neural states (for example, short-term synaptic plasticity). According to the dynamic coding framework, such hidden state transitions flexibly configure memory networks for memory-guided behavior and dissolve them equally fast to allow forgetting. We developed a perturbation approach to measure mnemonic hidden states in an electroencephalogram. By 'pinging' the brain during maintenance, we show that memory-item-specific information is decodable from the impulse response, even in the absence of attention and lingering delay activity. Moreover, hidden memories are remarkably flexible: an instruction cue that directs people to forget one item is sufficient to wipe the corresponding trace from the hidden state. In contrast, temporarily unattended items remain robustly coded in the hidden state, decoupling attentional focus from cue-directed forgetting. Finally, the strength of hidden-state coding predicts the accuracy of working-memory-guided behavior, including memory precision.

Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults.

BACKGROUND: There is emerging evidence that glutamatergic system dysfunction might play an important role in the pathophysiology of bipolar depression. This review focuses on the use of glutamate receptor modulators for depression in bipolar disorder. OBJECTIVES: 1. To assess the effects of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with bipolar disorder.2. To review the acceptability of ketamine and other glutamate receptor modulators in people with bipolar disorder who are experiencing acute depression symptoms. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR, to 9 January 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We cross-checked reference lists of relevant papers and systematic reviews. We did not apply any restrictions to date, language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing ketamine, memantine, or other glutamate receptor modulators with other active psychotropic drugs or saline placebo in adults with bipolar depression. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies for inclusion, assessed trial quality and extracted data. Primary outcomes for this review were response rate and adverse events. Secondary outcomes included remission rate, depression severity change scores, suicidality, cognition, quality of life, and dropout rate. We contacted study authors for additional information. MAIN RESULTS: Five studies (329 participants) were included in this review. All included studies were placebo-controlled and two-armed, and the glutamate receptor modulators - ketamine (two trials), memantine (two trials), and cytidine (one trial) - were used as add-on drugs to mood stabilisers. The treatment period ranged from a single intravenous administration (all ketamine studies), to repeated administration for memantine and cytidine (8 to 12 weeks, and 12 weeks, respectively). Three of the studies took place in the USA, one in Taiwan, and in one, the location was unclear. The majority (70.5%) of participants were from Taiwan. All participants had a primary diagnosis of bipolar disorder, according to the DSM-IV or DSM-IV-TR, and were in a current depressive phase. The severity of depression was at least moderate in all but one study.Among all glutamate receptor modulators included in this review, only ketamine appeared to be more efficacious than placebo 24 hours after the infusion for the primary outcome, response rate (odds ratio (OR) 11.61, 95% confidence interval (CI) 1.25 to 107.74; P = 0.03; I² = 0%, 2 studies, 33 participants). This evidence was rated as low quality. The statistically significant difference disappeared at three days, but the mean estimate still favoured ketamine (OR 8.24, 95% CI 0.84 to 80.61; 2 studies, 33 participants; very low quality evidence). We found no difference in response between ketamine and placebo at one week (OR 4.00, 95% CI 0.33 to 48.66; P = 0.28, 1 study; 18 participants; very low quality evidence).There was no significant difference between memantine and placebo in response rate one week after treatment (OR 1.08, 95% CI 0.06 to 19.05; P = 0.96, 1 study, 29 participants), two weeks (OR 4.88, 95% CI 0.78 to 30.29; P = 0.09, 1 study, 29 participants), four weeks (OR 5.33, 95% CI 1.02 to 27.76; P = 0.05, 1 study, 29 participants), or at three months (OR, 1.66, 95% CI 0.69 to 4.03; P = 0.26, I² = 36%, 2 studies, 261 participants). These findings were based on very low quality evidence.There was no significant difference between cytidine and placebo in response rate at three months (OR, 1.13, 95% CI 0.30 to 4.24; P = 0.86, 1 study, 35 participants; very low quality evidence).For the secondary outcome of remission, no significant differences were found between ketamine and placebo, nor between memantine and placebo. For the secondary outcome of change scores from baseline on depression scales, ketamine was more effective than placebo at 24 hours (MD -11.81, 95% CI -20.01 to -3.61; P = 0.005, 2 studies, 32 participants) but not at one or two weeks after treatment. There was no difference between memantine and placebo for this outcome.We found no significant differences in terms of adverse events between placebo and ketamine, memantine, or cytidine. There were no differences between ketamine and placebo, memantine and placebo, or cytidine and placebo in total dropouts. No data were available on dropouts due to adverse effects for ketamine or cytidine; but no difference was found between memantine and placebo. AUTHORS' CONCLUSIONS: Reliable conclusions from this review are severely limited by the small amount of data usable for analysis. The body of evidence about glutamate receptor modulators in bipolar disorder is even smaller than that which is available for unipolar depression. Overall, we found limited evidence in favour of a single intravenous dose of ketamine (as add-on therapy to mood stabilisers) over placebo in terms of response rate up to 24 hours; ketamine did not show any better efficacy in terms of remission in bipolar depression. Even though ketamine has the potential to have a rapid and transient antidepressant effect, the efficacy of a single intravenous dose may be limited. Ketamine's psychotomimetic effects could compromise study blinding; this is a particular issue for this review as no included study used an active comparator, and so we cannot rule out the potential bias introduced by inadequate blinding procedures.We did not find conclusive evidence on adverse events with ketamine. To draw more robust conclusions, further RCTs (with adequate blinding) are needed to explore different modes of administration of ketamine and to study different methods of sustaining antidepressant response, such as repeated administrations. There was not enough evidence to draw meaningful conclusions for the remaining two glutamate receptor modulators (memantine and cytidine). This review is limited not only by completeness of evidence, but also by the low to very low quality of the available evidence.