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Objective Several studies conducted in high-income countries have found an association between depressive symptoms and risky behaviors among adolescents. Evidence from low- and middle-income countries (LMICs), where 90% of the world's adolescents live, remains scarce. The objective of this review was to systematically review the evidence examining the association between depressive symptoms and risky behaviors among adolescents in LMICs. Method We searched 15 electronic databases for published or unpublished cohort and case-control studies about adolescents in LMICs. We applied no restrictions on date or language. The primary outcome was the association (odds ratio [ORs]) between depressive symptoms and risky sexual behavior and substance use. Secondary outcomes included delinquency, adverse school behavior, self-harm, and suicidal behavior. We pooled the ORs from all studies using the random-effect model. We assessed the quality of the studies using the Newcastle-Ottawa scale, and the strength of the overall body of evidence using GRADE. The study protocol was registered on PROSPERO (CRD42019131262). Results The searches yielded 31,148 potentially relevant studies. After screening, we included 33 records in the systematic review, of which 30 comprised the meta-analysis. All studies encompassed a total of 35,918 adolescents living in 17 LMICs: 5 from Africa, 7 from Asia, and 5 from Latin America and the Caribbean. We found that adolescents with depressive symptoms are more likely to engage in risky sexual behavior (OR 1.3, 95% CI: 1.1-1.5) and substance use (OR 1.8, 1.4-2.2) compared to non-depressed adolescents. Results for the secondary outcomes showed a similar pattern, with higher delinquency (OR 3.2, 1.8-5.6), self-harm (OR 4.4, 1.3-14.4), and suicidal behavior (OR 6.6, 2.3-18.9) among adolescents with depression compared to healthy adolescents. Conclusion This study suggests that adolescents with depression in LMICs carry a double burden: they both suffer from depression, and are at an increased risk of engaging in risky behaviors. This combination may lead to further psychological and physical health problems that persist over the life course, and may impose a health burden on society as a whole. Taken together, these findings highlight the urgent need for scalable and sustainable approaches to prevent and/or treat depression among adolescents in resource-poor settings.

Background Behaviour problems emerge early in childhood and place children at risk for later psychopathology. Objectives To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. Design A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. Setting Health visiting services in six NHS trusts in England. Participants A total of 300 at-risk children aged 12–36 months and their parents/caregivers. Interventions Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. Main outcome measures The primary outcome was the Preschool Parental Account of Children’s Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children’s Symptoms. Results In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children’s Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen’s d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children’s conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval –1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval –0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval –0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval –0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval –0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children’s Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children’s Symptoms was 1.73 [95% confidence interval –0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval –0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval –0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval –0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval –0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval –0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children’s Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children’s Symptoms. Limitations The proportion of participants with graduate-level qualifications was higher than among the general public. Conclusions VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. Trial registration Current Controlled Trials ISRCTN58327365. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 29. See the NIHR Journals Library website for further project information.

ObjectiveTo provide evidence on the effect of the COVID-19 pandemic on the mental health of young people who grew up in poverty in low/middle-income countries (LMICs).DesignA phone survey administered between August and October 2020 to participants of a population-based longitudinal cohort study established in 2002 comprising two cohorts born in 1994–1995 and 2001–2002 in Ethiopia, India (Andhra Pradesh and Telangana), Peru and Vietnam. We use logistic regressions to examine associations between mental health and pandemic-related stressors, structural factors (gender, age), and lifelong protective/risk factors (parent and peer relationship, wealth, long-term health problems, past emotional problems, subjective well-being) measured at younger ages.SettingA geographically diverse, poverty-focused sample, also reaching those without mobile phones or internet access.Participants10 496 individuals were approached; 9730 participated. Overall, 8988 individuals were included in this study; 4610 (51%) men and 4378 (49%) women. Non-inclusion was due to non-location or missing data.Main outcome measuresSymptoms consistent with at least mild anxiety or depression were measured by Generalized Anxiety Disorder-7 (≥5) or Patient Health Questionnaire-8 (≥5).ResultsRates of symptoms of at least mild anxiety (depression) were highest in Peru at 41% (32%) (95% CI 38.63% to 43.12%; (29.49–33.74)), and lowest in Vietnam at 9% (9%) (95% CI 8.16% to 10.58%; (8.33–10.77)), mirroring COVID-19 mortality rates. Women were most affected in all countries except Ethiopia. Pandemic-related stressors such as health risks/expenses, economic adversity, food insecurity, and educational or employment disruption were risk factors for anxiety and depression, though showed varying levels of importance across countries. Prior parent/peer relationships were protective factors, while long-term health or emotional problems were risk factors.ConclusionPandemic-related health, economic and social stress present significant risks to the mental health of young people in LMICs where mental health support is limited, but urgently needed to prevent long-term consequences.

Key Points Question Are specific phenotypes in preterm newborns associated with clinical, growth, and neurodevelopmental differences at age 2 years compared with term newborns? Findings In this cohort study of 6529 preterm and term newborns who were followed up from birth to age 2 years, 8 preterm-birth phenotypes were identified: no main maternal, fetal, or placental condition detected (35%); infections (21%); preeclampsia (12%); fetal distress (10%); intrauterine growth restriction (8%); severe maternal disease (6%); bleeding (5%); and congenital anomaly (4%). Each phenotype was associated with substantial differences in neonatal morbidity and infant outcomes. Meaning The study’s findings support the use of phenotypic classification for preterm births., Importance The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures. Objective To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years. Design, Setting, and Participants The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020. Exposures/Interventions Preterm-birth phenotypes. Main Outcomes and Measures Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool. Results A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype. Conclusions and Relevance Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity., This cohort study, part of the INTERBIO-21st Newborn Study, an extension of the INTERGROWTH-21st Project, examines the association between preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.

Objectives: Estimates of depression prevalence in pregnancy and postpartum are based on the Edinburgh Postnatal Depression Scale (EPDS) more than on any other method. We aimed to determine if any EPDS cutoff can accurately and consistently estimate depression prevalence in individual studies. Methods: We analyzed datasets that compared EPDS scores to Structured Clinical Interview for DSM (SCID) major depression status. Random‐effects meta‐analysis was used to compare prevalence with EPDS cutoffs versus the SCID. Results: Seven thousand three hundred and fifteen participants (1017 SCID major depression) from 29 primary studies were included. For EPDS cutoffs used to estimate prevalence in recent studies (≥9 to ≥14), pooled prevalence estimates ranged from 27.8% (95% CI: 22.0%–34.5%) for EPDS ≥ 9 to 9.0% (95% CI: 6.8%–11.9%) for EPDS ≥ 14; pooled SCID major depression prevalence was 9.0% (95% CI: 6.5%–12.3%). EPDS ≥14 provided pooled prevalence closest to SCID‐based prevalence but differed from SCID prevalence in individual studies by a mean absolute difference of 5.1% (95% prediction interval: 13.7%, 12.3%). Conclusion: EPDS ≥14 approximated SCID‐based prevalence overall, but considerable heterogeneity in individual studies is a barrier to using it for prevalence estimation., This study was funded by the Canadian Institutes of Health Research (CIHR, KRS‐140994). Ms. Lyubenova was supported by the Mitacs Globalink Research Internship Program. Ms. Neupane was supported by G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University. Drs. Levis and Wu were supported by Fonds de recherche du Québec‐Santé (FRQS) Postdoctoral Training Fellowships. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Ms. Azar was supported by a FRQS Masters Training Award. The primary study by Barnes et al. was supported by a grant from the Health Foundation (1665/608). The primary study by Beck et al. was supported by the Patrick and Catherine Weldon Donaghue Medical Research Foundation and the University of Connecticut Research Foundation. The primary study by Helle et al. was supported by the Werner Otto Foundation, the Kroschke Foundation, and the Feindt Foundation. Prof. Robertas Bunevicius, MD, PhD (1958‐2016) was Principal Investigator of the primary study by Bunevicius et al., but passed away and was unable to participate in this project. The primary study by Chaudron et al. was supported by a grant from the National Institute of Mental Health (grant K23 MH64476). The primary study by Tissot et al. was supported by the Swiss National Science Foundation (grant 32003B 125493). The primary study by Tendais et al. was supported under the project POCI/SAU‐ESP/56397/2004 by the Operational Program Science and Innovation 2010 (POCI 2010) of the Community Support Board III and by the European Community Fund FEDER. The primary study by Garcia‐Esteve et al. was supported by grant 7/98 from the Ministerio de Trabajo y Asuntos Sociales, Women's Institute, Spain. The primary study by Howard et al. was supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Numbers RP‐PG‐1210‐12002 and RP‐DG‐1108‐10012) and by the South London Clinical Research Network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The primary study by Phillips et al. was supported by a scholarship from the National Health and Medical and Research Council (NHMRC). The primary study by Nakić Radoš et al. was supported by the Croatian Ministry of Science, Education, and Sports (134‐0000000‐2421). The primary study by Navarro et al. was supported by grant 13/00 from the Ministry of Work and Social Affairs, Institute of Women, Spain. The primary study by Pawlby et al. was supported by a Medical Research Council UK Project Grant (number G89292999N). The primary study by Quispel et al. was supported by Stichting Achmea Gezondheid (grant number z‐282). Dr. Robertson‐Blackmore was supported by a Young Investigator Award from the Brain and Behavior Research Foundation and NIMH grant K23MH080290. The primary study by Rochat et al. was supported by grants from the University of Oxford (HQ5035), the Tuixen Foundation (9940), the Wellcome Trust (082384/Z/07/Z and 071571), and the American Psychological Association. Dr. Rochat receives salary support from a Wellcome Trust Intermediate Fellowship (211374/Z/18/Z). The primary study by Prenoveau et al. was supported by The Wellcome Trust (grant number 071571). The primary study by Stewart et al. was supported by Professor Francis Creed's Journal of Psychosomatic Research Editorship fund (BA00457) administered through University of Manchester. The primary study by Tandon et al. was funded by the Thomas Wilson Sanitarium. The primary study by Tran et al. was supported by the Myer Foundation who funded the study under its Beyond Australia scheme. Dr. Tran was supported by an early career fellowship from the Australian National Health and Medical Research Council. The primary study by Vega‐Dienstmaier et al. was supported by Tejada Family Foundation, Inc, and Peruvian‐American Endowment, Inc. Drs. Benedetti and Thombs were supported by FRQS researcher salary awards.

ObjectiveTo provide evidence on the effect of the COVID-19 pandemic on the mental health of adolescents and young adults who grew up in poverty in Low and Middle Income Countries (LMICs).DesignA phone survey implemented August-October 2020 to participants of a population-based cohort study since 2002 comprising two cohorts born in 1994-5 and 2001-2 in Ethiopia, India (Andhra Pradesh and Telangana), Peru and Vietnam. We examined associations between mental health and pandemic-related stressors, as well as structural factors (gender, location, wealth); and lifelong protective/risk factors (parent and peer relationship, past household wealth, long-term health problems, past emotional problems and subjective well-being) measured at younger ages.SettingA diverse, poverty focused sample, reaching those without mobile phones or internet access.Participants10,496 individuals were approached, 9,730 participated. Overall, 8,988 individuals were included in this study, 4,610 (51%) male and 4,378 (49%) female. Non-inclusion was due to non-location or missing data.Main outcome measuresAt least mild anxiety and depression were measured by Generalized Anxiety Disorder-7 (GAD-7, ≥5) and Patient Health Questionnaire-8 (PHQ-8, ≥5).ResultsRates of symptoms of at least mild anxiety (depression) were highest in Peru at 41% (32%) [95% CI, 38.63-43.12; (29.49-33.74)], and lowest in Vietnam at 9% (9%) [95% CI, 8.16-10.58; (8.33-10.77)], mirroring COVID-19 mortality rates. Females were most affected in all countries but Ethiopia. In all countries, pandemic-related stressors were associated with increased rates of anxiety and depression, though with varying levels of importance across countries. Prior parent and peer relationships were protective factors for mental health while having a long-term health problem or prior emotional problems were risk factors.ConclusionThe COVID-19 pandemic presents significant risks to the mental health of young people. Mental health support is limited in LMICs and young people have to date been lower priority for COVID-19 interventions.Strengths and limitations of this studyThe study uses data from adolescents and young adults who grew up in poverty in four LMICs which were diversely affected by the COVID-19 pandemic, therefore investigating a globally vulnerable, but understudied group both in terms of age and wealth.This study reaches a broad sample of young people who grew up in poverty, including those without internet or mobile phone access.A key strength is combining a broad range of pandemic-related stressors from survey data on experiences of COVID-19 with previously measured information on longer-term risk and protective factors, therefore contributing to a more complete picture of COVID-19 effects.A limitation of the study is that it does not have a directly comparable pre-COVID baseline for depression/anxiety, however, proxy variables are used as a baseline and the explanatory variables capture dynamics that happened during the pandemic.A further limitation is possible underreporting due to stigma associated with mental health, despite piloting and validation, as well as possible bias in self-reported experiences of pandemic-related stressors due to feelings of anxiety or depression.

This review aimed to determine: whether EF is affected in children and adolescents (2–24-years-old) with perinatal HIV infection, perinatal HIV exposure without infection, and behaviourally acquired HIV. A systematic review (PROSPERO number: CRD42017067813) was conducted using 11 electronic databases (01.01.1981–09.07.2019) and 8 conference websites. Primary quantitative studies with EF scores on cognitive tasks and/or behavioural report measures were included. Meta-analyses were performed by EF subtype and subpopulations compared. 1789 records were found. Sixty-one studies were included in the narrative synthesis; 32 (N = 7884 participants) were included in meta-analyses. There was a distinct pattern of reduced EF in those with perinatal HIV infection on antiretroviral therapy compared to controls: pooled effect sizes were largest for verbal and visuospatial working memory, with smaller effects on planning, inhibitory control and set-shifting. Data were limited for other HIV-affected subpopulations. Perinatal HIV infection is associated with reduced EF with varying effect sizes for the different EF subtypes.

INTRODUCTION There are increasing reports of a pediatric multi-system inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) that presents with varying clinical features, but includes features of Kawasaki disease or toxic shock syndrome. Symptoms include fever, rash, abdominal pain, vomiting, and diarrhea. Many patients present without any respiratory symptoms and testing for SARS-CoV-2 is often negative. METHODS A retrospective chart review was performed. RESULTS A 7-year-old previously healthy male presented with 3 days of fevers up to 102.4F, headaches, abdominal pain, and intractable vomiting. Both parents had tested positive for SARS-CoV-2 four weeks prior. Nasopharyngeal swab tested positive for SARS-CoV-2 RNA. Echocardiogram was normal. CT venogram of his head was negative for any pathology. He developed severe neck pain and persistent headache during his hospitalization. Soon after receiving hydroxychloroquine, he developed a facial rash and altered mental status with episodes of aphasia, agitation, and pinpoint pupils. He then became unresponsive with left gaze deviation. A non-contrast head CT and CT angiography were negative. He was given levetiracetam and cefazolin and transferred to the pediatric intensive care unit. An electroencephalogram (EEG) showed no epileptiform activity. Over the following 7 hours, the EEG demonstrated left frontotemporal slowing, which progressed into a loss of fast activity over the right hemisphere with increased delta activity in the left hemisphere, then abruptly changed to generalized voltage attenuation.He rapidly lost brainstem reflexes, developing fixed and dilated pupils. Repeat CT scan revealed diffuse cerebral edema with loss of gray-white differentiation. Lab results then were consistent with severe inflammation. An intracranial pressure monitor revealed pressures greater than 76 mmHg. His exam soon became consistent with brain death. Pathologic evaluation showed diffuse cerebral edema with perivascular mononuclear infiltrates. CONCLUSION The cause of this pediatric multi-system inflammatory syndrome is unclear and the mechanism by which SARS-CoV-2 affects the nervous system is unknown. Pediatric patients with COVID-19 and neurologic symptoms should be closely monitored as they can rapidly decline due to fulminant cerebral edema.

Highlights • One in ten women in this study were experiencing posttraumatic stress during the postpartum period. • For many women, posttraumatic stress during the postpartum period is unrelated to childbirth. • Prevalence and clinical characteristics of postpartum posttraumatic stress differ for posttraumatic stress related to childbirth and posttraumatic stress related to other stressors. • Different factors are associated with posttraumatic stress related to childbirth and posttraumatic stress related to other stressors. • Postpartum posttraumatic stress related to different stressors may require management protocols which differ in timing and focus., Background: Studies on prevalence and factors associated with postpartum posttraumatic stress (PTS) typically do not distinguish between PTS related to childbirth (PTS-C) and PTS related to other stressors (PTS-O). This study aimed to describe the prevalence, clinical characteristics, and factors associated with PTS-C and PTS-O in postpartum women. Methods: The study was a cross-sectional population-based survey of 16,000 postpartum women, selected at random from birth registrations in England to receive a postal questionnaire, including the Primary Care Posttraumatic Stress Disorder Screen. Results: Questionnaires were returned by 4,509 women. The median age was 32 years (IQR=29-36), 64% were married, 77% were UK-born, and 76% were White-British. Prevalence of PTS-C was 2.5% (95%CI:2.0-3.0) and prevalence of PTS-O was 6.8% (95%CI:6.0-7.8). Women with PTS-C were significantly more likely to report re-experiencing symptoms (Chi-Square=7.69,p

The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores ≥7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 ≥7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID)., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-140994). Drs. Thombs and Benedetti were supported by Fonds de recherche du Qu´ebec–Sant´e (FRQS) researcher salary awards. Dr. Levis was supported by a FRQS Postdoctoral Training Fellowship. Ms. Lyubenova was supported by theMitacs Globalink Research Internship Program. Ms. Neupane was supported by G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University. Dr. Wu was supported by a FRQS Postdoctoral Training Fellowship. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. Ms. Azar was supported by a FRQS Masters Training Award. The primary study by Barnes et al. was supported by a grant from the Health Foundation (1665/608). The primary study by Beck et al. was supported by the Patrick and Catherine Weldon Donaghue Medical Research Foundation and the University of Connecticut Research Foundation. The primary study by de Figueiredo et al. was supported by Fundacão de Amparo à Pesquisa do Estado de São Paulo. The primary study by Tendais et al. was supported under the project POCI/SAU-ESP/56397/2004 by the Operational Program Science and Innovation 2010 (POCI 2010) of the Community Support Board III and by the European Community Fund FEDER. The primary study by Helle et al. was supported by the Werner Otto Foundation, the Kroschke Foundation, and the Feindt Foundation. The primary study by Howard et al. was supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Numbers RPPG-1210-12002 and RP-DG-1108-10012) and by the South London Clinical Research Network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The primary study by Phillips et al. was supported by a scholarship from the National Health and Medical and Research Council (NHMRC). The primary study by Nakic´ Radoˇs et al. was supported by the Croatian Ministry of Science, Education, and Sports (134-0000000-2421). The primary study by Quispel et al. was supported by Stichting Achmea Gezondheid (grant number z-282). The primary study by Rochat et al. was supported by grants from the University of Oxford (HQ5035), the Tuixen Foundation (9940), the Wellcome Trust (082384/Z/07/Z and 071571), and the American Psychological Association. Dr. Rochat receives salary support from a Wellcome Trust Intermediate Fellowship (211374/Z/18/Z). The primary study by Prenoveau et al. was supported by The Wellcome Trust (grant number 071571). The primary study by Stewart et al. was supported by Professor Francis Creed’s Journal of Psychosomatic Research Editorship fund (BA00457) administered through University of Manchester. The primary study by Tandon et al. was funded by the Thomas Wilson Sanitarium. The primary study by Tran et al. was supported by the Myer Foundation who funded the study under its Beyond Australia scheme. Dr. Tran was supported by an early career fellowship from the Australian National Health and Medical Research Council. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The primary study by Vega-Dienstmaier et al. was supported by Tejada Family Foundation, Inc, and Peruvian-American Endowment, Inc. No other authors reported funding for primary studies or for their work on this study.

Highlights • Antenatal depression of moderate severity did not raise the risk of adverse birth outcomes. • Severe levels of antenatal depression were associated with lower APGAR scores and being SGA. • In this group of severe antenatal depression we found an increased risk for lower weight scores, being SGA and in the lower 10th centile for length for female newborns only. • To our knowledge this is the first paper to systematically examine the potential effects of increasing severity levels of antenatal depression on birth outcomes., Background We utilised data from the 2015 Pelotas Birth Cohort, a large prospective cohort in southern Brazil, to examine the association of moderate and severe antenatal depression with child birth outcomes and explore interactions with sociodemographic characteristics. Methods Data was available for n = 3046 participants and their infants. We measured antenatal depression using the Edinburgh Postnatal Depression Scale (EPDS, ≥13 for moderate and ≥17 for severe depression). Outcome measures included gestational age, birth weight, length and head circumference, using the Intergrowth-21st standards. We controlled for known confounders including obstetric risk. Results We did not find differences in childbirth outcomes by maternal depression status for participants with at least moderate depression, although there was an increased risk for female offspring to be small for gestational age (SGA, OR 2.33[1.37,3.97]). For severe depression (EPDS≥17) we found an increased risk for lower APGAR scores (OR 1.63[1.02,2.60]) and being SGA (OR 1.77[1.06,2.97], with an increased risk for female offspring in particular to be in lower weight centiles (−10.71 [−16.83,−4.60]), to be SGA (OR 3.74[1.89, 7.44]) and in the lower 10th centile for length (OR 2.19[1.25,3.84]). Limitations include the use of a maternal report questionnaire to ascertain depressive symptoms. Conclusions In this recent large longitudinal cohort in Brazil we did not find independent effects of depression on adverse birth outcomes or interactions with sociodemographic characteristics. We found an increased risk of being SGA for female offspring of women with moderate and severe depression, in line with other research suggesting females may be more susceptible to antenatal disturbances. Funding This work was supported by the Wellcome Trust, United Kingdom (095582), the Brazilian National Research Council (CNPq) and the Coordination for the Improvement of Higher Education Personnel (CAPES). EN was supported by the UK Economic and Social Research Council GCRF Postdoctoral Fellowship (ES/P009794/1).

Background The effect of the period before a mother’s death on child survival has been assessed in only a few studies. We conducted a comparative investigation of the effect of the timing of a mother’s death on child survival up to age five years in rural South Africa. Methods We used discrete time survival analysis on data from two HIV-endemic population surveillance sites (2000–2015) to estimate a child’s risk of dying before and after their mother’s death. We tested if this relationship varied between sites and by availability of antiretroviral therapy (ART). We assessed if related adults in the household altered the effect of a mother’s death on child survival. Findings 3,618 children died from 2000–2015. The probability of a child dying began to increase in the 7–11 months prior to the mother’s death and increased markedly in the 3 months before (2000–2003 relative risk = 22.2, 95% CI = 14.2–34.6) and 3 months following her death (2000–2003 RR = 20.1; CI = 10.3–39.4). This increased risk pattern was evident at both sites. The pattern attenuated with ART availability but remained even with availability at both sites. The father and maternal grandmother in the household lowered children’s mortality risk independent of the association between timing of mother and child mortality. Conclusions The persistence of elevated mortality risk both before and after the mother’s death for children of different ages suggests that absence of maternal care and abrupt breastfeeding cessation might be crucial risk factors. Formative research is needed to understand the circumstances for children when a mother is very ill or dies, and behavioral and other risk factors that increase both the mother and child’s risk of dying. Identifying families when a mother is very ill and implementing training and support strategies for other members of the household are urgently needed to reduce preventable child mortality.

Background Health risk behaviors during adolescence may cluster into patterns that might be predicted by specific factors, among which HIV may have an important role. Method In a cross-sectional study conducted between 2017 and 2018, clustering of HRB and its associated factors was investigated in rural Kenya among 588 adolescents (36% perinatally HIV infected; 28% perinatally HIV exposed but uninfected; and 36% HIV unexposed/uninfected). Latent class analysis of 22 behaviors followed by multinomial logistic regression were conducted. Four risk behavior classes were identified. Results No significant differences were found in behavioral class membership across the three HIV groups (p = 0.366). The risk of membership to the higher risk behavioral classes relative to class 1 (the substance and drug abstinent low risk takers) increased with older adolescent age (p = 0.047), increased among adolescent who experienced mental distress (p p p = 0.0037) was found to be protective. Conclusion The results highlight a need to include screening and interventions for internalizing mental health problems and deficits in executive functioning, as well as steps to involve family members and communities to address psychosocial risk factors in adolescents in Kenya.

Introduction/Purpose Transcranial doppler (TCD) is a bedside modality to rapidly assess the presence of vasospasm or stenosis of cerebral arteries. However, manual TCD requires a trained sonographer which may not be available in all healthcare settings. The LUCID TCD system aims to expedite and enhance TCD blood flow measurements through semi-autonomous acquisition. This study aims to evaluate the safety and feasibility of the LUCID TCD system for detection of vasospasm. Materials and Methods Peak velocities of the middle cerebral arteries (MCA) were measured and a velocity greater than 120 cm/s was considered indicative of vasospasm. To determine feasibility, maximal MCA velocities from LUCID TCD were compared to computer tomography angiography, and the Cohen’s Kappa value was calculated to gauge the agreement between the two modalities. Safety was assessed through quantifying the number of complications with central venous lines (CVL) or external ventricular drains (EVD) attributable to the LUCID device. Results Nine patients (average age = 66 yrs) with subarachnoid hemorrhages or aneurysms underwent a total of 21 LUCID TCDs to assess the MCAs for vasospasm. The autonomous motion of the LUCID TCD ultrasound transducers did not displace or impinge on CVLs/EVDs. Moreover, LUCID acquired maximum MCA velocities and angiography moderately agree with a Cohen’s Kappa value of 0.61 (p=0.005). Conclusions This investigation demonstrates that LUCID TCD as a modality to probe for MCA vasospasm is a viable option as LUCID maximum MCA velocities and angiography are moderately congruent. Additionally, LUCID TCD is safe to use clinically as it poses minimal risk to a patient‘s CVL or EVD. Disclosures K. Clare: None. A. Stein: None. J. Cooper: None. C. Gandhi: None. C. Bowers: None. C. Cole: None. J. Santarelli: None. J. Pisapia: None. F. Al-Mufti: None.

SummaryBackgroundGrowth faltering has been associated with poor intellectual performance. The relative strengths of associations between growth in early and in later childhood remain underexplored. We examined the association between growth in childhood and adolescence and adult human capital in five low- or middle-income countries (LMICs).MethodsWe analyzed data from six prospective birth cohorts of five LMICs (Brazil, Guatemala, India, the Philippines, and South Africa). We assessed the associations of measures of height and relative weight at four ages (birth, at around age 2 years, mid-childhood (MC), adulthood), with two dimension of adult human capital (schooling attainment and IQ).FindingsIn site- and sex-pooled analyses, size at birth and linear growth from birth to around 2 years of age were positively associated with schooling attainment and adult IQ. Linear growth from age 2 years to MC and from MC to adulthood was not associated with higher school attainment or IQ. Change in relative weight in early childhood was not associated with either outcome. Relative weight in MC and in adulthood were inversely associated with schooling attainment but were not associated with adult IQ.InterpretationLinear growth in the first 1,000 days is a predictor of schooling attainment and IQ in adulthood in LMICs. Linear growth in later periods was not associated with either of these outcomes. Changes in relative weight had inconsistent association with schooling and IQ in adulthood.FundingBill and Melinda Gates Foundation (OPP1164115)Research in contextEvidence before this studyEarly life growth faltering has been associated with poor cognitive and intellectual performance in childhood and poorer schooling outcomes in children and adults. There is a paucity of data about how growth in specific age intervals over the course of childhood and adolescence relates to attained schooling and adult cognitive performance.We conducted a literature search using the terms (growth [Title/Abstract]) AND ((school [Title/Abstract] OR schooling [Title/Abstract]) AND (intelligence [Title/Abstract] OR IQ [Title/Abstract]) OR (human capital [Title/Abstract]) in Pubmed. The search yielded 536 publications from 1965 to 2020. We screened titles and selected 31 publications that included linear growth and our outcomes of interest, namely school attainment and intelligence quotient (IQ). Additionally, we checked reference lists of selected articles and identified eleven papers that were not displayed in the initial electronic query. We therefore reviewed 42 abstracts and identified 24 unique studies conducted in low and middle-income countries (LMICs). Fourteen of them investigated the association of birth size and/or early-life size with schooling or IQ, or with both outcomes during childhood. Three studies investigated the association between linear growth in early childhood and schooling and intelligence in adults, one studied the association between early-life undernutrition and IQ in early adulthood and another six publications investigated the association between growth and school attainment in adults. Economists have also studied the relationship between stunting or linear growth and schooling in LMICs, but to our knowledge not the relative importance of growth during specific age intervals.Added value of this studyThis is an analysis of the associations between child and adolescent growth and two dimensions of human capital (schooling attainment and IQ) in adulthood in six birth cohorts from five LMICs. The evidence of long-term associations of linear growth with adult IQ is scarce and the few published studies have analyzed data from a single country. In the present study, we found that size at birth and linear growth from birth to around 2 years of age were positively associated with both schooling and IQ in adulthood. Linear growth between early and mid-childhood (MC)was not associated with higher school attainment or IQ in adjusted models. Linear growth from MC to adulthood was not associated with IQ in men or women, and was inversely associated with schooling attainment in women only. Change in relative weight in early childhood was positively associated with schooling attainment only in minimally adjusted models. Relative weight measures in MC and adulthood were inversely associated with schooling attainment. Change in relative weight between MC and adulthood was not associated with adult IQ.Implications of all the available evidenceWe confirmed in multiple cohorts that birth size and linear growth from birth to age 2 years are predictors of schooling attainment and adult IQ. Linear growth in early life was the strongest predictor of these two human capital dimensions in adulthood among individuals in LMICs. We did not find evidence that supports the notion that linear growth in adolescence contributes to a better cognitive performance in adulthood. Thus, our results inform the more effective timing of nutritional and other interventions to improve linear growth and human capital in the long-term.

Contains fulltext : 222303.pdf (Publisher’s version ) (Closed access) The perception of infant emotionality, one aspect of temperament, starts to form in infancy, yet the underlying mechanisms of how infant emotionality affects adult neural dynamics remain unclear. We used a social reward task with probabilistic visual and auditory feedback (infant laughter or crying) to train 47 nulliparous women to perceive the emotional style of six different infants. Using functional neuroimaging, we subsequently measured brain activity while participants were tested on the learned emotionality of the six infants. We characterized the elicited patterns of dynamic functional brain connectivity using Leading Eigenvector Dynamics Analysis and found significant activity in a brain network linking the orbitofrontal cortex with the amygdala and hippocampus, where the probability of occurrence significantly correlated with the valence of the learned infant emotional disposition. In other words, seeing infants with neutral face expressions after having interacted and learned their various degrees of positive and negative emotional dispositions proportionally increased the activity in a brain network previously shown to be involved in pleasure, emotion, and memory. These findings provide novel neuroimaging insights into how the perception of happy versus sad infant emotionality shapes adult brain networks. 11 p.

Low-income and middle-income countries have increasingly relied on cash transfer programmes to expand social protection among the most poor and vulnerable people. Many of these cash transfer programmes have given cash directly to adolescents to incentivise behaviour that improve a range of health and social outcomes. The evidence for the effectiveness of these programmes has been mixed. Some studies show cash transfer to be effective in promoting desired behaviours among adolescents—such as school participation and reducing sexually transmitted infections—whereas others find no evidence for an effect. One possible reason for these mixed results is that cash transfer programmes targeting adolescents have not taken into account the many biological, cognitive, and social changes that occur during this transitional period, thus failing to incorporate a developmental perspective in the design.

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21st Project. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to 6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for “emotional reactivity”. The positive effect of EBF and age at weaning on gross motor, running and climbing scores was strongest among children with the highest scores in maternal closeness proxy indicators. EBF, late weaning and maternal closeness, associated with advanced motor and vision maturation, independently influence autonomous behaviours in healthy children.

Background: This study evaluated whether clinical and economic outcomes from CBT for child anxiety disorders in the context of maternal anxiety disorders are improved by adding treatment focused on (i) maternal anxiety disorders, or (ii) mother-child interactions. Methods: 211 children (7 – 12 years, 85% White British, 52% female) with a primary anxiety disorder, whose mothers also had a current anxiety disorder, were randomised to receive (i) child-focused CBT with non-specific control interventions (CCBT+Con), (ii) CCBT with CBT for the maternal anxiety disorder (CCBT+MCBT), or (iii) CCBT with an intervention targeting the mother-child interaction (CCBT+MCI). A cost-utility analysis from a societal perspective was conducted using mother/child combined Quality Adjusted Life Years (QALYs). [Trial registration: https://doi.org/10.1186/ISRCTN19762288]. Results: MCBT was associated with immediate reductions in maternal anxiety compared to the non-specific control; however, after children had also received CCBT, maternal outcomes in the CCBT+MCI and CCBT+Con arms improved and CCBT+MCBT was no longer superior. Neither CCBT+MCBT nor CCBT+MCI conferred a benefit over CCBT+Con in terms of child anxiety disorder diagnoses post-treatment [primary outcome] (adj RR: 1.22 (95% CI 0.88, 1.67), p = .23; adj RR: 1.21 (95% CI 0.88, 1.65), p = .24 respectively) or global improvement ratings (adj RR 1.25 (95% CI 0.99, 1.57), p = .06; adj RR 1.18 (95% CI 0.93, 1.50), p = .17) or six and 12 months later. No significant differences between the groups were found on the main economic outcome measures (child/mother combined QALY mean difference: CCBT+MCBT vs CCBT+Con: -0.04 (95% CI -0.12, 0.04), p = 0.29; CCBT+MCI vs CCBT+Con: 0.02 (95% CI -0.05, -0.09), p = 0.54). CCBT+MCI was associated with non-significantly higher costs than CCBT (mean difference: £154 (95% CI -£1239, £1547), p = 0.83) but, when taking into account sampling uncertainty, it may be cost-effective compared with CCBT alone. Conclusions: Good outcomes were achieved for children and their mothers across treatment arms. There was no evidence of significant clinical benefit from supplementing CCBT with either CBT for the maternal anxiety disorder or treatment focussed on mother-child interactions, but the addition of MCI (and not MCBT) may be cost-effective. Keywords: Child; anxiety; mother; parent-child interaction; CBT.

ObjectivesTo describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project.DesignPopulation-based cohort study, the INTERGROWTH-21st Project.SettingBrazil, India, Italy, Kenya and the UK.Participants1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes.Primary measuresScaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones.ResultsScaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA’s cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA’s negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22–30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (ConclusionsFrom this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes.

Measuring executive function (EF) among adults is important, as the cognitive processes involved in EF are critical to academic achievement, job success and mental health. Current evidence on measurement and structure of EF largely come from Western, Educated, Industrialized, Rich and Democratic (WEIRD) countries. However, measuring EF in low-and-middle-income countries (LMICs) is challenging, because of the dearth of EF measures validated across LMICs, particularly measures that do not require extensive training, expensive equipment, or professional administration. This paper uses data from three LMIC cohorts to test the feasibility, validity and reliability of EF assessment in adults using three sub-tests (representing key components of EF) of the NIH Toolbox Cognitive battery. For each cohort, all three EF measures (inhibition, flexibility and working memory) loaded well onto a unidimensional latent factor of EF. Factor scores related well to measures of fluid intelligence, processing speed and schooling. All measures showed good test-retest reliability across countries. This study provides evidence for a set of sound measures of EF that could be used across different cultural, language and socio-economic backgrounds in future LMIC research. Furthermore, our findings extend conclusions on the structure of EF beyond those drawn from WEIRD countries.

Background Heparin induced thrombocytopenia Type II (HIT-II) is a dangerous thromboembolic complication of heparin therapy. The current literature on incidence and outcomes of HIT-II in aneurysmal subarachnoid hemorrhage (aSAH) patients remains sparse. Objective We report our institution's incidence and outcomes of HIT-II in aSAH patients. Methods We performed a retrospective cohort study at an academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography. Diagnosis of HIT-II was determined by positive results on both heparin PF4-platelet antibody ELISA (anti-PF4) and serotonin release assay (SRA). Results 204 patients met inclusion criteria. Seven patients (7/204, 3.5%) underwent laboratory testing, three of whom met clinical criteria. HIT-II incidence was confirmed in two of these seven patients (2/204, 0.98%), who had high BMI and T4 scores. Conclusion Our institution's report of HIT-II incidence in aSAH patients is lower than previously reported in this population and more closely parallels HIT-II incidence in the general and surgical ICU setting. Widely-accepted American College of Chest Physicians (ACCP) clinical diagnostic criteria in conjunction with anti-PF4 and SRA testing is the gold standard of clinical diagnosis of HIT-II in aSAH patients.

Despite being home to a large population of vulnerable children there is a dearth of population-based evidence on childhood mental disorders in sub-Saharan Africa. Parent and child mental health are rarely measured concurrently, despite potential for confounding with other risk factors, including parental HIV. Using the parent-report Child Behaviour Checklist (CBCL) we assessed children’s mental health in a population-based cohort of 1536 HIV-negative children (31% HIV-exposed, 18% HIV-affected, 51% HIV-unexposed) aged 7–11 years. CBCL was scored using CBCL Rating-to-Score software. A binary indicator was determined using the clinical threshold ≥ 65. We modelled mental disorders using logistic regression, including covariates associated with the mother, child, household, and parenting. Structural equation modelling techniques also derived continuous latent variables representing the underlying mental health and parent-relationship constructs. Prevalence of conduct disorders (11.8%) was high, regardless of HIV exposure, while HIV-affected children had increased odds of affective disorders. Maternal depression increased odds of externalising disorders; maternal anxiety was associated with affective and anxiety disorders. Mother–child relationship dysfunction increased odds of all disorders, including: affective [aOR = 5.1 (2.6–9.9)]; oppositional [aOR = 7.9 (4.0–15.5)]; conduct [aOR = 4.3 (2.6–7.2)] disorders. Food insecurity and male gender increased odds of somatic disorders; breastfeeding halved odds of conduct disorders. In the latent model, associations were substantially stronger for the mother–child relationship and externalising disorders (Oppositional 0.464 p < 0.001; Conduct 0.474 p =

BackgroundLittle is known about the social and emotional well-being of children whose fathers have been deployed to the conflicts in Iraq/Afghanistan or who have post-traumatic stress disorder (PTSD).AimsTo examine the emotional and behavioural well-being of children whose fathers are or have been in the UK armed forces, in particular the effects of paternal deployment to the conflicts in Iraq or Afghanistan and paternal PTSD.MethodFathers who had taken part in a large tri-service cohort and had children aged 3–16 years were asked about the emotional and behavioural well-being of their child(ren) and assessed for symptoms of PTSD via online questionnaires and telephone interview.ResultsIn total, 621 (67%) fathers participated, providing data on 1044 children. Paternal deployment to Iraq or Afghanistan was not associated with childhood emotional and behavioural difficulties. Paternal probable PTSD were associated with child hyperactivity. This finding was limited to boys and those under 11 years of age.ConclusionsThis study showed that adverse childhood emotional and behavioural well-being was not associated with paternal deployment but was associated with paternal probable PTSD.Declaration of interestN.T.F. is a trustee of the Warrior Programme, a charity supporting ex-service personnel and their families. She is also a member of the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee of Combat Stress, a charity supporting ex-service personnel and their families, and President of the Royal Society of Medicine. S.W. is partially funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England (PHE), in collaboration with the University of East Anglia and Newcastle University.

Background: Maternal postnatal depression (PND) is a risk factor for offspring depression in adulthood. However, few longitudinal studies have examined the role of maternal nurturing parenting behaviours in the association between maternal PND and offspring depression in adulthood. Methods: We examined pathways from maternal PND measured using self-reported Edinburgh Postnatal Depression Scale at 8 weeks to offspring ICD-10 depression diagnosed using the Clinical Interview Schedule-Revised computerised assessment at 24 years through maternal-reported nurturing behaviours concerning feeding, sleeping and crying measured from pregnancy to age 3 years 6 months in 5,881 members of the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children. Results: The fully adjusted model revealed an indirect effect from PND to adult offspring depression through the combination of all parenting factors (probit regression coefficient [B]=0.038, 95% confidence interval [CI] 0.005, 0.071); however, there was no evidence of a direct effect from early maternal PND to offspring depression once the indirect effect via parenting factors was accounted for (B=0.009, 95%CI -0.075, 0.093). Specificity analyses revealed indirect effects through maternal worries about feeding (B=0.019, 95%CI 0.003, 0.035, p=0.010) and maternal perceptions and responses to crying (B=0.018, 95%CI 0.004, 0.032, p=0.012). Conclusions: The adverse impact of maternal PND on offspring depression in early adulthood was explained by maternal nurturing behaviours concerning feeding, crying and sleeping in early childhood. Residual confounding and measurement error likely limit reliable conclusions. If found causal, interventions providing support to reduce worries around maternal nurturing behaviours and treating depression could reduce adverse outcomes in adult offspring of depressed mothers.

Postnatal depression is common and may have severe consequences for women and their children. Locally validated screening tools are required to identify at-risk women in marginalised populations. The Edinburgh Postnatal Depression Scale (EPDS) is one of the most frequently used tools globally. This cross-sectional study assessed the validity and acceptability of the EPDS in Karen and Burmese among postpartum migrant and refugee women on the Thai–Myanmar border. The EPDS was administered to participants and results compared with a diagnostic interview. Local staff provided feedback on the acceptability of the EPDS through a focus group discussion. Results from 670 women showed high accuracy and reasonable internal consistency of the EPDS. However, acceptability to local staff was low, limiting the utility of the EPDS in this setting despite its good psychometrics. Further work is required to identify a tool that is acceptable and sensitive to cultural manifestations of depression in this vulnerable population.

When interacting with an infant, parents intuitively enact a range of behaviours that support infant communicative development. These behaviours include altering speech, establishing eye contact and mirroring infant expressions and are argued to occur largely in the absence of conscious intent. Here, we describe studies investigating early, pre-conscious neural responses to infant cues, which we suggest support aspects of parental intuitive behaviour towards infants. This work has provided converging evidence for rapid differentiation of infant cues from other salient social signals in the adult brain. In particular, the orbitofrontal cortex may be important in supporting quick orienting responses and privileged processing of infant cues, processes fundamental to intuitive parenting behaviour.

With the widespread use of antiretroviral therapy and successful prevention of mother-to-child transmission the development of HIV-negative children with HIV-positive parents has become an important focus. There is considerable evidence that children’s developmental risk is heightened because a parental HIV-diagnosis is associated with a range of potential problems such as depression, stigma and financial difficulties. Up to a third of children in sub-Saharan Africa (SSA) are cared for by an HIV-positive parent or caregiver. We review the mechanisms by which HIV affects parenting including its negative effects on parental responsiveness in the early years of parenting and parental avoidant coping styles and parenting deficits in the later years. We describe low-cost parenting interventions suited for low resourced HIV endemic settings.

Whether it is the sound of a distressed cry or the image of a cute face, infants capture our attention. Parents and other adults alike are drawn into interactions to engage in play, nurturance and provide care. Responsive caregiving behaviour is a key feature of the parent-infant relationship, forming the foundation upon which attachment is built. Infant cues are considered to be 'innate releasers' or 'motivational entities' eliciting responses in nearby adults (Lorenz 1943; Murray, 1979) [42,43]. Through the advent of modern neuroimaging, we are beginning to understand the initiation of this motivational state at the neurobiological level. In this review, we first describe a current model of the 'parental brain', based on functional MRI studies assessing neural responses to infant cues. Next, we discuss recent findings from temporally sensitive techniques (magneto- and electroencephalography) that illuminate the temporal dynamics of this neural network. We focus on converging evidence highlighting a specific role for the orbitofrontal cortex in supporting rapid orienting responses to infant cues. In addition, we consider to what extent these neural processes are tied to parenthood, or whether they might be present universally in all adults. We highlight important avenues for future research, including utilizing multiple levels of analysis for a comprehensive understanding of adaptive caregiving behaviour. Finally, we discuss how this research can help us understand disrupted parent-infant relationships, such as in situations where parents' contingent responding to infant cues is disrupted; for example, in parental depression or anxiety where cognitive attentional processes are disrupted.

Introduction Children's understanding of HIV and death in epidemic regions is under-researched. We investigated children's death-related questions post maternal HIV-disclosure. Secondary aims examined characteristics associated with death-related questions and consequences for children's mental health. Methods HIV-infected mothers (N = 281) were supported to disclose their HIV status to their children (6–10 years) in an uncontrolled pre-post intervention evaluation. Children's questions post-disclosure were collected by maternal report, 1–2 weeks post-disclosure. 61/281 children asked 88 death-related questions, which were analysed qualitatively. Logistic regression analyses examined characteristics associated with death-related questions. Using the parent-report Child Behaviour Checklist (CBCL), linear regression analysis examined differences in total CBCL problems by group, controlling for baseline. Results Children's questions were grouped into three themes: ‘threats’; ‘implications’ and ‘clarifications’. Children were most concerned about the threat of death, mother's survival, and prior family deaths. In multivariate analysis variables significantly associated with asking death-related questions included an absence of regular remittance to the mother (AOR 0.25 [CI 0.10, 0.59] p = 0.002), mother reporting the child's initial reaction to disclosure being “frightened” (AOR 6.57 [CI 2.75, 15.70] p=, Highlights • Children living in HIV epidemic communities are exposed to death at young ages. • Primary-school aged children understand information on HIV, illness and death. • Intervention training successfully prepared mothers to communicate about death. • Communication about death did not increase children’s mental health problems. • HIV disclosure creates opportunities to communicate with and reassure children.

Objective Sleep is an important marker of healthy development and has been associated with emotional, behavioral, and cognitive development. There is limited longitudinal data on children's sleep with only a few reports from low- and middle-income countries (LMICs). We investigate sleep parameters and associated sociodemographic characteristics in a population-based longitudinal study in Pelotas, Brazil. Methods Data from the Pelotas 2004 Birth Cohort were used (N = 3842). Infant sleep was collected through maternal report at 3, 12, 24, and 48 months: sleep duration, bed and wake time, nighttime awakenings, co-sleeping and sleep disturbances (24 and 48 months). Results Compared to children in high-income countries (HICs), children in Brazil showed a substantial shift in rhythms with later bed and wake times by approximately 2 hours. These remain stable throughout the first 4 years of life. This population also shows high levels of co-sleeping which remain stable throughout (49.0–52.2%). Later bedtime was associated with higher maternal education and family income. Higher rates of co-sleeping were seen in families with lower income and maternal education and for children who were breastfed. All other sleep parameters were broadly similar to data previously reported from HICs. Conclusion The shift in biological rhythms in this representative community sample of children in Brazil challenges our understanding of optimal sleep routine and recommendations., Highlights • Biological rhythms are shifted with later bedtime by approximately 2 h (22.18 hours). • Later bedtime is associated with higher maternal education and family income. • High levels of co-sleeping are prevalent until 4 years of age (49% at 3 months to 52% at 4 years). • Co-sleeping was more prevalent in families with lower income and maternal education.

Carotid blowout syndrome (CBS) is a rare complication following resection of head and neck cancers, especially after re-irradiation for a recurrent tumor, and is associated with very high mortality (15–100%).1 Our patient with squamous cell cancer of the tongue had undergone glossectomy and left radical neck dissection, followed by radiation. Six months after radiation, the patient had radiation necrosis of the overlying myofascial muscle flap. The carotid artery did not have any healthy …

The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13–21 years) in rural Mpumalanga Province, South Africa, during 2011–2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: –0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW.

Purpose: Parenthood represents a major biological, social and environmental life change. Mental health disorders are common in parents and impact both the parent and their offspring. However, the relationship between parenthood and mental health, and the direction of these effects are poorly understood. Method: Longitudinal data from the Pelotas 1982 birth cohort, Southern Brazil, on >3000 individuals was used to investigate the association between number of children by age 30 years and mental health disorders using DSM-IV diagnoses at age 30 years, suicidal risk and the change in symptoms using repeated measures (using the SRQ-20) from age 19 to 30 years. Results: Mothers, but not fathers, with higher number of children by age 30 years were at a substantially increased risk of a wide range of mental health disorders compared to women with no children (adjusted odds ratio (OR) for suicidal plans: 5.99, 95%CI 2.51 to 14.30, pConclusions: Mothers, particularly those with multiple children, are at risk of a wide range of mental health disorders. The mechanisms to explain these risks are yet to be elucidated, however, the risk of mental health disorders was not replicated in fathers, which would be expected if residual confounding explained observed associations. Thus, multiparous mothers represent a high-risk group and should be prioritised for supportive interventions.

Background The 2016 World Health Organization Antenatal Guidelines and the 2015 South African Maternal and Child Health Guidelines recommend one early antenatal ultrasound scan to establish gestational age and to detect multiple pregnancies and fetal abnormalities. Prior research indicates that ultrasound can also increase parental-fetal attachment. We aim to establish whether, compared to routine care, messages to promote parental attachment and healthy child development, conducted during one or two pregnancy ultrasounds improve early child development and growth, exclusive breastfeeding, parental-child interactions and pre- and post-natal clinic attendance. Methods The effect of messages to sensitise mothers and fathers to fetal development will be tested in a 3-armed randomised trial with 100 mothers and their partners from Soweto-Johannesburg in each arm. The primary outcome is child development at 6 months post-natal. Secondary outcomes include infant feeding, parental attachment and interaction, parental mental health and infant growth, assessed at 6 weeks and 6 months. Parents in Arm 1 receive a fetal ultrasound

BackgroundThe 2016 World Health Organization Antenatal Guidelines and the 2015 South African Maternal and Child Health Guidelines recommend one early antenatal ultrasound scan to establish gestational age and to detect multiple pregnancies and fetal abnormalities. Prior research indicates that ultrasound scan can also increase parental–fetal attachment. We aim to establish whether, compared to routine care, messages to promote parental attachment and healthy child development, conducted during one or two pregnancy ultrasound scans, improve early child development and growth, exclusive breastfeeding, parental–child interactions and prenatal and postnatal clinic attendance.MethodsThe effect of messages to sensitise mothers and fathers to fetal development will be tested in a three-armed randomised trial with 100 mothers and their partners from Soweto, Johannesburg in each arm. The primary outcome is child development at 6 months postnatally. Secondary outcomes include infant feeding, parental attachment and interaction, parental mental health and infant growth, assessed at 6 weeks and 6 months. Parents in Arm 1 receive a fetal ultrasound scan DiscussionEvidence from high-income countries suggests that first-time prospective mothers and fathers enjoy seeing their fetus during ultrasound scan and that it is an emotional experience. A number of studies have found that ultrasound scan increases maternal attachment during pregnancy, a predictor of positive parent–infant interactions which, in turn, promotes healthy infant development. It is generally agreed that studies are needed which follow up parental–child behaviour and healthy child development postnatally, include fathers and examine the construct in a wider diversity of settings, especially in low and middle-income countries. Testing the added benefits of pregnancy ultrasound scan for child development is a gap that the proposed trial in South Africa seeks to address.Trial registrationPan African Clinical Trials Registry,PACTR201808107241133. Registered on 15 August 2018.

BackgroundChildren in low-income and middle-income countries (LMICs) who remain in school have better health and employment outcomes. South Africa, like many LMICs, has a secondary school completion rate under 50%, leaving room for improvement if we can identify factors that affect educational attainment. This is the first longitudinal study to examine the effects of childhood mental health and cognitions on educational outcomes in LMIC.MethodsUsing the Strengths and Difficulties Questionnaire (SDQ) and Cognitive Triad Inventory for Children (CTI-C), we assessed the psychological functioning and cognition of children aged 10–12 in rural South Africa. We linked that data with measures of educational progress collected 5 years later and examined associations between educational progress and (1) behavioural and emotional problems and (2) cognitive interpretations, adjusting for possible confounders.ResultsEducational data were available for 443 individuals. 92% (n=408) of individuals had advanced three or fewer grades in 7 years. Having more positive cognitions (CTIC-C) was positively associated with progressing at least three grade levels (adjusted OR 1.43, 95% CI 1.14 to 1.79). There was no evidence for an association between emotional and behavioural problems (SDQ) and educational progress (OR 0.90, 95% CI 0.72 to 1.11).ConclusionIf children in LMICs can develop more positive perspectives, they may be able to stay in school longer. Cognitions can be modified, and future studies should test interventions that work to improve cognition in childhood, guided, for example, by principles of cognitive–behavioural therapy.

Many adults diagnosed with a life-threatening condition have children living at home; they and their partners face the dual challenge of coping with the diagnosis while trying to maintain a parenting role. Parents are often uncertain about how, when, and what to tell their children about the condition, and are fearful of the effect on their family. There is evidence that children are often aware that something is seriously wrong and want honest information. Health-care professionals have a key role in supporting and guiding parents and caregivers to communicate with their children about the diagnosis. However, the practical and emotional challenges of communicating with families are compounded by a scarcity of evidence-based guidelines. This Review considers children's awareness and understanding of their parents' condition, the effect of communication around parental life-threatening condition on their wellbeing, factors that influence communication, and the challenges to achieving effective communication. Children's and parents' preferences about communication are outlined. An expert workshop was convened to generate principles for health-care professionals, intended as practical guidance in the current absence of empirically derived guidelines.

When a child is diagnosed with a life-threatening condition, one of the most challenging tasks facing health-care professionals is how to communicate this to the child, and to their parents or caregivers. Evidence-based guidelines are urgently needed for all health-care settings, from tertiary referral centres in high-income countries to resource limited environments in low-income and middle-income countries, where rates of child mortality are high. We place this Review in the context of children's developing understanding of illness and death. We review the effect of communication on children's emotional, behavioural, and social functioning, as well as treatment adherence, disease progression, and wider family relationships. We consider the factors that influence the process of communication and the preferences of children, families, and health-care professionals about how to convey the diagnosis. Critically, the barriers and challenges to effective communication are explored. Finally, we outline principles for communicating with children, parents, and caregivers, generated from a workshop of international experts.

Interpreting and responding to an infant's emotional cues is a fundamental parenting skill. Responsivity to infant cues is frequently disrupted in depression, impacting negatively on child outcomes, which underscores its importance. It is widely assumed that women, and in particular mothers, show greater attunement to infants than do men. However, empirical evidence for sex and parental status effects, particularly in relation to perception of infant emotion, has been lacking. In this study, men and women with and without young infants were asked to rate valence in a range of infant facial expressions, on a scale of very positive to very negative. Results suggested complex interaction effects between parental status, sex, and the facial expression being rated. Mothers provided more positive ratings of the happy expressions and more extreme ratings of the intense emotion expressions than fathers, but non-mothers and non-fathers did not. Low-level depressive symptoms were also found to correlate with more negative ratings of negative infant facial expressions across the entire sample. Overall, these results suggest that parental status might have differential effects on men and women's appraisal of infant cues. Differences between fathers’ and mothers’ perceptions of infant emotion might be of interest in understanding variance in interaction styles, such as proportion of time spent in play.

Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. Results: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased. Conclusion: Different interviews may not classify major depression equivalently., This study was funded by the Canadian Institutes of Health Research (CIHR, KRS-140994). Ms. Levis was supported by a CIHR Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Awards. Ms. Rice was supported by a Vanier Canada Graduate Scholarship. Dr. Wu was supported by an Utting Postdoctoral Fellowship from the Jewish General Hospital, Montreal, Quebec, Canada. Ms. Azar was supported by a Fonds de recherche du Québec - Santé (FRQS) Masters Training Award. Mr. Bhandari was supported by a studentship from the Research Institute of the McGill University Health Centre. The primary study by Alvarado et al. was supported by the Ministry of Health of Chile. The primary study by Barnes et al. was supported by a grant from the Health Foundation (1665/608). The primary study by Beck et al. was supported by the Patrick and Catherine Weldon Donaghue Medical Research Foundation and the University of Connecticut Research Foundation. The primary study by Helle et al. was supported by the Werner Otto Foundation, the Kroschke Foundation, and the Feindt Foundation. Prof. Robertas Bunevicius, MD, PhD (1958–2016) was principal investigator of the primary study by Bunevicius et al. but passed away and was unable to participate in this project. The primary study by Couto et al. was supported by the National Counsel of Technological and Scientific Development (CNPq; Grant 444254/2014-5) and the Minas Gerais State Research Foundation (FAPEMIG; Grant APQ-01954-14). The primary study by Chaudron et al. was supported by a grant from the National Institute of Mental Health (Grant K23 MH64476). The primary study by Figueira et al. was supported by the Brazilian Ministry of Health and by the National Counsel of Technological and Scientific Development (CNPq; Grant 403433/2004-5). The primary study by de Figueiredo et al. was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo. The primary study by Tissot et al. was supported by the Swiss National Science Foundation (Grant 32003B 125493). The primary study by Fernandes et al. was supported by grants from the Child: Care Health and Development Trust and the Department of Psychiatry, University of Oxford, Oxford, UK, and by the Ashok Ranganathan Bursary from Exeter College, University of Oxford. Dr. Fernandes was supported by a National Institute for Health Research (NIHR) academic clinical fellowship. The primary study by Tendais et al. was supported under the project POCI/SAU-ESP/56397/2004 by the Operational Program Science and Innovation 2010 (POCI 2010) of the Community Support Board III and by the European Community Fund FEDER. The primary study by Fisher et al. was supported by a grant under the Invest to Grow Scheme from the Australian Government Department of Families, Housing, Community Services and Indigenous Affairs. The primary study by Garcia-Esteve et al. was supported by Grant 7/98 from the Ministerio de Trabajo y Asuntos Sociales, Women's Institute, Spain. The primary study by Howard et al. was supported by the NIHR under its Programme Grants for Applied Research Programme (Grants RP-PG-1210-12002 and RPDG-1108-10012) and by the South London Clinical Research Network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The primary study by Phillips et al. was supported by a scholarship from the National Health and Medical and Research Council (NHMRC). The primary study by Roomruangwong et al. was supported by the Ratchadaphiseksomphot Endowment Fund 2013 of Chulalongkorn University (CU-56-457-HR). The primary study by Naki c Radoš et al. was supported by the Croatian Ministry of Science, Education, and Sports. The primary study by Navarro et al. was supported by Grant 13/00 from the Ministry of Work and Social Affairs, Institute of Women, Spain. The primary study by Usuda et al. was supported by Grants-in-Aid for Young Scientists (A) from the Japan Society for the Promotion of Science (primary investigator: Daisuke Nishi, MD, PhD) and by an Intramural Research Grant for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry, Japan. Dr. Robertson-Blackmore was supported by a Young Investigator Award from the Brain and Behavior Research Foundation and NIMH Grant K23MH080290. The primary study by Rochat et al. was supported by grants from University of Oxford (HQ5035), the Tuixen Foundation (9940), the Wellcome Trust (082384/Z/07/Z and 071571), and the American Psychological Association. Dr. Rochat receives salary support from a Wellcome Trust Intermediate Fellowship (211374/Z/18/Z). The primary study by Rowe et al. was supported by the diamond Consortium, beyondblue Victorian Centre of Excellence in Depression and Related Disorders. The primary study by Comasco et al. was supported by funds from the Swedish Research Council (VR: 521-2013-2339, VR: 523-2014-2342), the Swedish Council for Working Life and Social Research (FAS: 2011-0627), the Marta Lundqvist Foundation (2013, 2014), and the Swedish Society of Medicine (SLS-331991). The primary study by Prenoveau et al. was supported by the Wellcome Trust (Grant 071571). The primary study by Stewart et al. was supported by Professor Francis Creed's Journal of Psychosomatic Research Editorship fund (BA00457) administered through University of Manchester. The primary study by Su et al. was supported by grants from the Department of Health (DOH94F044 and DOH95F022) and the China Medical University and Hospital (CMU94-105, DMR-92-92, and DMR94-46). The primary study by Tandon et al. was supported by the Thomas Wilson Sanitarium. The primary study by Tran et al. was supported by the Myer Foundation who funded the study under its Beyond Australia scheme. Dr. Tran was supported by an early career fellowship from the Australian National Health and Medical Research Council. The primary study by Vega-Dienstmaier et al. was supported by Tejada Family Foundation, Inc. and Peruvian-American Endowment, Inc. The primary study by Yonkers et al. was supported by a National Institute of Child Health and Human Development grant (5 R01HD045735). Drs. Benedetti and Thombs were supported by FRQS researcher salary awards.