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Background Simulated interventions using observational data have the potential to inform policy and public health interventions where randomised controlled trials are not feasible. National childhood obesity policy is one such area. Overweight and obesity are primarily caused by energy-rich and low-nutrient diets that contribute to a positive net energy imbalance. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated whether causal modelling techniques could be applied to simulate the potential impact of policy-relevant calorie-reduction interventions on population prevalence and inequalities in obesity in childhood. Methods Predicted probabilities of obesity at age 11 (UK90 cut offs) were estimated from logistic marginal structural models (MSM) accounting for observed calorie consumption at age 7 and confounding, overall and by maternal occupational social class. A series of population intervention scenarios were modelled to simulate daily calorie-reduction interventions that differed in effectiveness, targeting mechanism and programme uptake level. Results The estimated effect of maternal social class on obesity after accounting for confounding and observed calorie intake was provided by the controlled direct effect (CDE), in which, 18.3% of children were living with obesity at age 11 years,. A universal simulation to lower median intake to the estimated average requirement (EAR) (a 6.1% reduction in daily calories) with 75% uptake reduced overall obesity prevalence by 0.6%; there was little impact on inequalities. A targeted intervention to limit consumption to the EAR for children with above average intake reduced population obesity prevalence at 11 years by 1.5% but inequalities remained broadly unchanged. A targeted intervention for children of low-income families reduced prevalence by 0.7% and was found to slightly reduce inequalities. Conclusions MSMs allow estimation of effects of simulated calorie-reduction interventions on childhood obesity prevalence and inequalities, although estimates are limited by the accuracy of reported calorie intake. Further work is needed to understand causal pathways and opportunities for intervention. Nevertheless, simulated intervention techniques have promise for informing national policy where experimental data are not available.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits. The work of H. Tiemeier is further supported by a European Union’s Horizon 2020 research and innovation program (Contract grant number: 633595, DynaHealth) and a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). https://www.nwo.nl/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background Adolescent girls face several challenges relating to menstruation and its proper management. Lack of adequate sanitary products, inadequate water supply, and privacy for changing sanitary pads continue to leave adolescent girls with limited options for safe and proper menstrual hygiene in many low-income settings, including Ethiopia. These situations are also compounded by societal myths, stigmas surrounding menstruation, and discriminatory social norms. This systematic review and meta-analysis aimed to estimate the pooled proportion of safe menstrual hygiene management among adolescent girls in Ethiopia using the available studies. Methods We searched PubMed, Google Scholar, African Journal Online (AJOL), Hinari, Science Direct, ProQuest, Direct of Open Access Journals, POPLINE, and Cochrane Library database inception to May 31, 2021. Studies reporting the proportion of menstrual hygiene management among adolescent girls in Ethiopia were considered. The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the included studies. Since the included studies revealed considerable heterogeneity, a random effect meta-analysis model was used to estimate the pooled proportion of menstrual hygiene management (MHM). Results Of 1,045 identified articles, 22 studies were eligible for analysis (n = 12,330 participants). The pooled proportion (PP) of safe MHM in Ethiopia was 52.69% (95%CI: 44.16, 61.22). The use of commercial menstrual absorbents was common 64.63% (95%CI: 55.32, 73.93, I2 99.2%) followed by homemade cloth 53.03% (95%CI: 22.29, 83.77, I2 99.2%). Disposal of absorbent material into the latrine was the most common practice in Ethiopia 62.18% (95%CI: 52.87, 71.49, I2 98.7%). One in four girls reported missing one or more school days during menstruation (PP: 32.03%, 95%CI: 22.65%, 41.40%, I2 98.2%). Conclusion This study revealed that only half of the adolescent girls in Ethiopia had safe MHM practices. To ensure that girls in Ethiopia can manage menstruation hygienically and with dignity, strong gender-specific water, sanitation, and hygiene (WASH) facilities along with strong awareness creation activities at every level are needed.

Purpose The purpose of this study was to characterize the nasopharyngeal microbiota of infants with possible and confirmed pertussis compared to healthy controls. Methods This prospective study included all infants Results Twelve confirmed cases, 21 possible cases and 9 healthy controls were included. Confirmed whooping cough was primarily driven by detection of Bordetella with no other major changes on nasopharyngeal microbiota. Possible cases had limited abundance or absence of Bordetella and a distinctive microbiota with lower bacterial richness and diversity and higher rates of viral co-infection than both confirmed cases and healthy controls. Bordetella reads determined by 16S rRNA gene sequencing were found in all 12 confirmed cases (100%), 3 out of the 21 possible cases (14.3%) but in any healthy control. Conclusion This study supports the usefulness of 16S rRNA gene sequencing for improved sensitivity on pertussis diagnosis compared to real-time PCR and to understand other microbial changes occurring in the nasopharynx in children

Background There is a lack of nationally representative estimates for the consequences of early childhood undernutrition on preadolescent outcomes in India. Understanding this relationship is helpful to develop interventions that not only prevent child undernutrition but also mitigate its consequences. Methods and findings In this cohort study, we analyzed prospectively gathered data from 2 waves of the India Human Development Survey (IHDS) to investigate the association of undernutrition during early childhood (0 to 5 years) in 2004 to 2005 with physical and cognitive outcomes during preadolescent (8 to 11 years) years in 2011 to 2012. These surveys interviewed 41,554 households across all 33 states and union territories in India in 2004 to 2005 and reinterviewed 83% of the households in 2011 to 2012. Primary exposure was assessed using the Composite Index of Anthropometric Failure (CIAF) based on 2004 to 2005 survey. Primary outcomes were short stature (height-for-age z-score [HAZ], Apurv Soni and co-workers study child nutrition and developmental outcomes in India., Author summary Why was this study done? India has the largest number of undernourished children under the age of 5. Previous studies report an absence of gender disparities among child undernutrition in India despite well-documented disparities in adulthood. Current national programs for addressing child undernutrition focus on the first 5 years of life and do not include gender-focused interventions. What did the researchers do and find? We carried out a population-based cohort study based on data gathered prospectively from nationally representative survey of 41,554 households in India in 2004 to 2005 and a follow-up in 2011 to 2012 among 83% of the same households. This study leverages India’s only nationally representative panel dataset to report that undernutrition in the first 5 years of life is associated with increased odds of adverse physical outcomes, i.e., having short stature and being very thin and cognitive outcomes, i.e., unable to read and do arithmetic during preadolescent years. Female children who were undernourished were the most vulnerable for experiencing these adverse outcomes, and the gender disparities widened with age during the preadolescent period. As an example, the adjusted probability of short stature for undernourished female children increased from 31% among 8 year olds to 45% among 11 year olds. There was no such increase observed among male children. Presence of a woman in the household with more than secondary level of education mitigated the disadvantage associated with both being undernourished and being a female child. What do these findings mean? Sex differences in physical and cognitive outcomes emerge during the preadolescent period and are associated with early childhood nutrition. Higher level of female education within the household is an important protective factor for these disparities. Elevation of women’s status through improved female education should be central to the national level programs in India focused on maternal and child health.

Background Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring. Methods and findings Between April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies. Conclusions This mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children., Andrea Weckman and co-workers study associations between children’s neurodevelopmental outcomes and malaria in pregnancy., Author summary Why was this study done? Large human cohorts have linked maternal infection during pregnancy (without congenital infection) to an increased risk for neurocognitive deficits and neuropsychiatric disease in exposed children. Excessive maternal immune activation, irrespective of pathogen, is thought to mediate this effect. Millions of pregnant women are at risk for malaria infection each year. To our knowledge, the impact of malaria during pregnancy on child neurodevelopment has not been systematically studied in a clinical setting. What did the researchers do and find? We conducted an observational cohort follow-up study nested within a larger randomized controlled trial with detailed records of malaria in pregnancy to examine the impact of malaria in pregnancy on neurocognitive development in exposed children. To our knowledge, our data provide the first indication in a clinical cohort that malaria in pregnancy may be a previously unrecognized risk factor for neurodevelopmental delay. Furthermore, the association of systemic inflammation with reduced neurocognitive scores highlights a potential mechanistic pathway through which malaria in pregnancy could be affecting fetal neurodevelopment. What do these findings mean? There are millions of children in malaria-endemic regions who are not currently meeting their developmental potential. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental delay in children exposed in utero. Our findings suggest that scaling up efforts to prevent malaria infection could be an effective strategy to protect mother–baby dyads from poor developmental outcomes. Larger trials powered to address potential residual confounding, with a longer follow-up period and more diverse neurocognitive and neuropsychiatric tests, are required to confirm and extend these findings.

Nathan Ford and co-authors discuss the systematic identification of research gaps in improving HIV service delivery.

Background Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). Methods and findings This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (p = 0.02), obesity (HR 1.13; 95% CI 1.05–1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08–2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86–1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82–2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06–1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC. Conclusions In this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART. Trial registration number ISRCTN11780826.

Background Brazil has made great progress in reducing child mortality over the past decades, and a parcel of this achievement has been credited to the Bolsa Família program (BFP). We examined the association between being a BFP beneficiary and child mortality (1–4 years of age), also examining how this association differs by maternal race/skin color, gestational age at birth (term versus preterm), municipality income level, and index of quality of BFP management. Methods and findings This is a cross-sectional analysis nested within the 100 Million Brazilian Cohort, a population-based cohort primarily built from Brazil’s Unified Registry for Social Programs (Cadastro Único). We analyzed data from 6,309,366 children under 5 years of age whose families enrolled between 2006 and 2015. Through deterministic linkage with the BFP payroll datasets, and similarity linkage with the Brazilian Mortality Information System, 4,858,253 children were identified as beneficiaries (77%) and 1,451,113 (23%) were not. Our analysis consisted of a combination of kernel matching and weighted logistic regressions. After kernel matching, 5,308,989 (84.1%) children were included in the final weighted logistic analysis, with 4,107,920 (77.4%) of those being beneficiaries and 1,201,069 (22.6%) not, with a total of 14,897 linked deaths. Overall, BFP participation was associated with a reduction in child mortality (weighted odds ratio [OR] = 0.83; 95% CI: 0.79 to 0.88; p < 0.001). This association was stronger for preterm children (weighted OR = 0.78; 95% CI: 0.68 to 0.90; p < 0.001), children of Black mothers (weighted OR = 0.74; 95% CI: 0.57 to 0.97; p < 0.001), children living in municipalities in the lowest income quintile (first quintile of municipal income: weighted OR = 0.72; 95% CI: 0.62 to 0.82; p < 0.001), and municipalities with better index of BFP management (5th quintile of the Decentralized Management Index: weighted OR = 0.76; 95% CI: 0.66 to 0.88; p < 0.001). The main limitation of our methodology is that our propensity score approach does not account for possible unmeasured confounders. Furthermore, sensitivity analysis showed that loss of nameless death records before linkage may have resulted in overestimation of the associations between BFP participation and mortality, with loss of statistical significance in municipalities with greater losses of data and change in the direction of the association in municipalities with no losses. Conclusions In this study, we observed a significant association between BFP participation and child mortality in children aged 1–4 years and found that this association was stronger for children living in municipalities in the lowest quintile of wealth, in municipalities with better index of program management, and also in preterm children and children of Black mothers. These findings reinforce the evidence that programs like BFP, already proven effective in poverty reduction, have a great potential to improve child health and survival. Subgroup analysis revealed heterogeneous results, useful for policy improvement and better targeting of BFP., In a cross-sectional analysis, Dandara Ramos, Nívea B. da Silva, and colleagues investigate the association between the Bolsa Família conditional cash transfer program, and mortality of children under 5 years of age., Author summary Why was this study done? In 2019 alone, globally 5.2 million children died before reaching 5 years of age. Scientific research has pointed out conditional cash transfers as an effective policy to reduce child mortality rates, especially in low- and middle-income countries. No other study to our knowledge has analyzed the association between Brazil’s Bolsa Família program (the world’s largest conditional cash transfer program) and child mortality (ages 1–4 years). What did the researchers do and find? We analyzed a sample of 6,309,366 children under 5 years of age, between 2006 and 2015. Our study used methods to control for self-selection bias and explored results across subpopulations according to maternal education, maternal race/skin color, gestational age at birth, and municipal indicators of wealth and the quality of cash transfer management. We found a significant association between participating in the Bolsa Família program and a lower risk of mortality for children aged 1 to 4 years. This association was stronger for preterm children, children of Black mothers, children living in municipalities in the lowest income quintile, and children living in cities where the Bolsa Família program was best administered. What do these findings mean? Our findings are consistent with previous studies, pointing to a significant association between participation in conditional cash transfers and positive child health outcomes, such as lower child mortality. The greater association among children in more vulnerable situations suggests conditional cash transfers may help to promote equity, with stronger results among those in more need. In the future, other studies should aim to validate our findings by employing more rigorous impact evaluation techniques to support causal inference.

Background Approximately 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Women’s empowerment may help provide inputs of nurturing care for early development and growth by building caregiver capacity and family support. We examined the associations between women’s empowerment and child development, growth, early learning, and nutrition in sub-Saharan Africa (SSA). Methods and findings We pooled data on married women (15 to 49 years) and their children (36 to 59 months) from Demographic and Health Surveys that collected data on child development (2011 to 2018) in 9 SSA countries (N = 21,434): Benin, Burundi, Cameroon, Chad, Congo, Rwanda, Senegal, Togo, and Uganda. We constructed a women’s empowerment score using factor analysis and assigned women to country-specific quintile categories. The child outcomes included cognitive, socioemotional, literacy–numeracy, and physical development (Early Childhood Development Index), linear growth (height-for-age Z-score (HAZ) and stunting (HAZ, Lilia Bliznashka and co-workers study empowerment of women and associated child health outcomes in sub-Saharan Africa., Author summary Why was this study done? Nearly 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Children require multiple health, nutrition, early learning, and care inputs to reach their full developmental and growth potential. Women’s empowerment may help provide these inputs by increasing shared caregiving, building caregiver capacity, and improving family support. Even though women’s empowerment is predictive of better child health, nutrition, and growth, less is known about the relationship between women’s empowerment and child development and early learning outcomes. What did the researchers do and find? We pooled Demographic and Health Surveys data from married women (15 to 49 years) and their children (36 to 59 months) in 9 sub-Saharan African countries to investigate the association between women’s empowerment and child development, growth, early learning, and nutrition outcomes. Our results showed that higher women’s empowerment was predictive of better child cognitive development, growth, and nutrition. More empowered women and their partners also had access to more learning resources and provided more stimulation activities to their child. What do these findings mean? Our findings indicate that improving women’s empowerment is one potential strategy to help provide the nutrition and early learning inputs children require to reach their full developmental and growth potential. Efforts to improve early child development and growth should consider the role of women’s empowerment in improving early learning and nutrition outcomes. Future research should assess the longitudinal and causal relationships between women’s empowerment and child development, growth, early learning, and nutrition outcomes.

Background Impaired growth among infants remains one of the leading nutrition problems globally. In this study, we aimed to compare the growth trajectory rate and evaluate growth trajectory characteristics among children, who are HIV exposed uninfected (HEU) and HIV unexposed uninfected (HUU), under two years in Zambia. Method Our study used data from the ROVAS II study (PACTR201804003096919), an open-label randomized control trial of two verses three doses of live, attenuated, oral RotarixTM administered 6 &10 weeks or at 6 &10 weeks plus an additional dose at 9 months of age, conducted at George clinic in Lusaka, Zambia. Anthropometric measurements (height and weight) were collected on all scheduled and unscheduled visits. We defined linear growth velocity as the rate of change in height and estimated linear growth velocity as the first derivative of the mixed effect model with fractional polynomial transformations and, thereafter, used the second derivative test to determine the peak height and age at peak heigh. Results We included 212 infants in this study with median age 6 (IQR: 6–6) weeks of age. Of these 97 (45.3%) were female, 35 (16.4%) were stunted, and 59 (27.6%) were exposed to HIV at baseline. Growth velocity was consistently below the 3rd percentile of the WHO linear growth standard for HEU and HUU children. The peak height and age at peak height among HEU children were 74.7 cm (95% CI = 73.9–75.5) and 15.5 months (95% CI = 14.7–16.3) respectively and those for HUU were 73 cm (95% CI = 72.1–74.0) and 15.6 months (95% CI = 14.5–16.6) respectively. Conclusion We found no difference in growth trajectories between infants who are HEU and HUU. However, the data suggests that poor linear growth is universal and profound in this cohort and may have already occurred in utero.

Toxocariasis is worldwide endemic parasitic anthropozoonosis with high risk to those in in vulnerable populations and particularly during pregnancy and childhood. Although the prevalence of anti-Toxocara spp. antibodies has been extensively studied, risk factors of pregnant women of different ages remains to be established. This study was designed to i) assess the presence of anti-Toxocara spp. antibodies in pregnant women that presented to the public health system in a city of southeastern Brazil, and ii) determine the risk factors for toxocariasis in adolescent and adult pregnant women. This cross-sectional study included 280 pregnant women (71 aged up to and including 17 years [adolescents] and 209 aged 18 years and older [adults]). Pregnant women voluntarily agreed to complete a socioeconomic questionnaire and provide serum samples. Anti-Toxocara IgG antibodies were screened by Enzyme-Linked Immunosorbent Assay (ELISA). Univariable and multivariable logistic regression models were performed to assess the risks for toxocariasis. Overall, 20.7% of pregnant women were seropositive (33.8% of adolescents and 16.3% of adults). Prevalence in pregnant adolescents was 2.6-fold higher than in adults (Odds ration [OR]: 2.63; 95% CI: 1.42–4.86, p = 0.003). Multivariate analysis revealed that contact with soil (p = 0.01; OR = 4.76) and being in the first trimester of pregnancy (p = 0.03; OR = 0.17) had significantly greater risk of toxocariasis for adolescents, and attainment of elementary through middle school education level (p = 0.05; OR = 8.33) was a risk factor in adult pregnant women. Toxocariasis is likely underreported and neglected in adolescent pregnant women; this age group should always be monitored for toxocariasis and correspondent clinical signs, particularly at late pregnancy., Author summary Toxocariasis has been described as a worldwide cosmopolitan anthropozoonosis with high risk to those in in vulnerable populations and particularly during pregnancy and childhood. Although the prevalence of anti-Toxocara spp. antibodies has been extensively studied, risk factors of pregnant women of different ages remains to be established. This study was designed to assess the presence of anti-Toxocara spp. antibodies in pregnant women presented to the public health system in a city of southeastern Brazil, and determine the risk factors for toxocariasis in adolescent and adult pregnant women. Our results show that Toxocara spp. seroprevalence in pregnant women may be influenced by age; with younger age identified as a risk factor for Toxocara spp. seropositivity. Toxocariasis is likely underreported and neglected in adolescent pregnant women; this age group should always be monitored for toxocariasis and correspondent clinical signs, particularly at late pregnancy. This data may be useful as background information for educational programs on toxocariasis prevention in pregnant women, particularly adolescents.

Julie Bines discusses an accompanying study by Sheila Isanaka and colleagues on nutrient supplementation and immune responses to rotavirus vaccination.

Background There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCVs) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among undervaccinated Australian children. Methods and findings Birth and vaccination records, IPD notifications, and hospitalisations were individually linked for children aged, In an observational study, Jocelyn Chan and colleagues investigate associations between pneumococcal conjugate vaccine coverage and incidence of invasive pneumococcal disease and pneumonia among children under 5 years in Australia., Author summary Why was this study done? Pneumococcal conjugate vaccines (PCVs) reduce the burden of pneumococcal disease in vaccinated and unvaccinated populations through both direct and indirect (herd) effects. The indirect effects of a vaccine comprise a substantial component of overall vaccine impact, contributing to the cost-effectiveness of the vaccine, but little is known about what factors contribute to herd protection, including vaccination coverage. In this study, we examined associations between PCV coverage and indirect effects within diverse populations in Australia. What did the researchers do and find? Using a large dataset of 1.3 million children from 2 states in Australia, we quantified the relationship between PCV coverage within small geographical units and indirect protection against pneumococcal disease. We also performed similar analyses for infants too young to be fully vaccinated, urban, rural, and Indigenous populations. There were strong inverse relationships between PCV coverage and the incidence of severe invasive disease due to vaccine types and pneumonia hospitalisations among undervaccinated children, i.e., higher coverage was associated with greater reductions in disease due to indirect effects. We also found substantial indirect effects at relatively low levels of PCV coverage. We estimated that 50% and 90% coverage of 7-valent PCV (PCV7) among children under 5 years of age prevented almost three-quarters (72.5%, 95% confidence interval [CI] 51.6 to 84.4) and almost all (95.2%, 95% CI 89.4 to 97.8) of PCV7-type severe invasive disease, respectively. For pneumonia, we estimated that 50% and 90% coverage was sufficient to prevent one-third (33.3%, 95% CI 27.3 to 38.8) and about half (51.7%, 95% CI 43.7 to 58.6) of all-cause pneumonia hospitalisations among undervaccinated children. These trends were similar for children less than 4 months old, urban, rural, and Indigenous populations, although these effects were smaller for rural and Indigenous populations. There was also a trend towards decreasing incidence of PCV13-type IPD among undervaccinated children as PCV13 coverage increased. What do these findings mean? Our results challenge existing assumptions that high PCV coverage is required to achieve substantial indirect protection. Understanding the determinants of indirect effects are particularly urgent as countries that have controlled vaccine-type pneumococcal disease consider using reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to significantly lower program costs while maintaining vaccine impact, providing indirect protection is achieved and preserved.

Background Water, sanitation and hygiene (WASH) interventions should support infant growth but trial results are inconsistent. Frequently, interventions do not consider behaviours or transmission pathways specific to age. A household playspace (HPS) is one intervention component which may block faecal-oral transmission. This study was a two-armed, parallel-group, randomised, controlled feasibility trial of a HPS in rural Ethiopia. It aimed to recommend proceeding to a definitive trial. Secondary outcomes included effects on infant health, injury prevention and women’s time. Methods November 2019−January 2020 106 households were identified and assessed for eligibility. Recruited households (N = 100) were randomised (blinded prior to the trial start) to intervention or control (both n = 50). Outcomes included recruitment, attrition, adherence, and acceptability. Data were collected at baseline, two and four weeks. Findings Recruitment met a priori criteria (≥80%). There was no loss to follow-up, and no non-use, meeting adherence criteria (both ≤10%). Further, 48.0% (95% CI 33.7−62.6; n = 24) of households appropriately used and 56.0% (41.3−70.0; n = 28) cleaned the HPS over four weeks, partly meeting adherence criteria (≥50%). For acceptability, 41.0% (31.3−51.3; n = 41) of infants were in the HPS during random visits, failing criteria (≥50%). Further, the proportion of HPS use decreased during some activities, failing criteria (no decrease in use). A modified Barrier Analysis described good acceptability and multiple secondary benefits, including on women’s time burden and infant injury prevention. Interpretation Despite failing some a priori criteria, the trial demonstrated mixed adherence and good acceptability among intervention households. A definitive trial to determine efficacy is warranted if recommended adjustments are made. Funding People In Need; Czech Development Agency. Trial registration RIDIE-ID-5de0b6938afb8., Author summary This research tested a new way to protect infants and young children from infections that are caused by pathogens in human and animal faeces. It tested the feasibility of using a household playspace to reduce infection by creating a hygienic environment for children to play-in in rural Ethiopia. The results show that the household playspace was well accepted, used regularly and cleaned well by participants in the study. The study also suggests a potential positive impact in reducing diarrhoea. Based on these results, we suggest that a larger scale trial be conducted to conclusively assess whether a household playspace can protect young children and infants from infection in rural Ethiopia or similar contexts.

Background India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to, Author summary Rubella infection during the first trimester of pregnancy can affect fetus, resulting in spontaneous abortion, stillbirth or birth of a baby with a combination of birth defects known as congenital rubella syndrome (CRS). Vaccination with rubella containing vaccine (RCV) is recommended as one of the strategies for eliminating rubella/CRS. The Southeast Asia region has set a target to eliminate rubella/CRS by 2023. Towards this goal, India completed nationwide immunization campaigns using measles-rubella vaccine during 2017–19, targeting children aged 9 months to

Objectives Health care professionals regularly struggle with issues relating to confidentiality and consent for physical and/or mental health issues among adolescents. We investigate late adolescents’ own and assumed parental preferences towards health-care related confidentiality and consent. Methods We analyzed online survey data of four vignettes from 463 first-year university students at KU Leuven (Flanders, Belgium). We used paired samples t-tests to assess the (in)consistency between attitudes of late adolescents and their assumed parental attitudes, independent samples t-tests to estimate gender differences, and binomial logistic regressions to analyze the association of assumed parental preferences with late adolescents’ own preferences. Results Attitudinal inconsistencies were present in all vignettes. Late adolescents were significantly more in favor of confidentiality and adolescent consent than what they believed their parents were. Gender differences were limited. Binomial logistic regressions indicated that assumed parental preferences were strongly associated with late adolescents’ own preferences. Conclusions Findings suggest a clear difference between late adolescents’ preferences and assumed parental preferences: they believe that their parents are less inclined to favor confidentiality and adolescent consent. We also find that this difference depends on the case, indicating that there is no such thing as general ‘confidentiality preferences’. Rather, a decision- and/or context-specific perspective should be adopted.

Background Praziquantel (PZQ) is currently the only recommended drug for infection and disease caused by the schistosome species that infects humans; however, the current tablet formulation is not suitable for pre-school age children mainly due to its bitterness and the large tablet size. We assessed the palatability of two new orally disintegrating tablet (ODT) formulations of PZQ. Methodology This randomized, single-blind, crossover, swill-and-spit palatability study (NCT02315352) was carried out at a single school in Tanzania in children aged 6–11 years old, with or without schistosomiasis infection as this was not part of the assessment. Children were stratified according to age group (6–8 years or 9–11 years) and gender, then randomized to receive each formulation in a pre-specified sequence. Over 2 days, the children assessed the palatability of Levo-Praziquantel (L-PZQ) ODT 150 mg and Racemate Praziquantel (Rac-PZQ) ODT 150 mg disintegrated in the mouth without water on the first day, and L-PZQ and Rac-PZQ dispersed in water and the currently available PZQ 600 mg formulation (PZQ-Cesol) crushed and dispersed in water on the second day. The palatability of each formulation was rated using a 100 mm visual analogue scale (VAS) incorporating a 5-point hedonic scale, immediately after spitting out the test product (VASt = 0 primary outcome) and after 2–5 minutes (VASt = 2–5). Principal findings In total, 48 children took part in the assessment. Overall, there was no reported difference in the VASt = 0 between the two ODT formulations (p = 0.106) without water. Higher VASt = 0 and VASt = 2–5 scores were reported for L-PZQ ODT compared with Rac-PZQ ODT in older children (p = 0.046 and p = 0.026, respectively). The VASt = 0 and VASt = 2–5 were higher for both ODT formulations compared with the standard formulation (p, Author summary Schistosomiasis or Bilharzia is among the top debilitating parasitic diseases in endemic developing countries. It presents either in urinary or intestinal form. The diseases’ mode of transmission is waterborne through contact with infested water. The main groups affected in developing countries are women and children due to their frequent contact with water. WHO introduced a mass drug administration program whereby drugs are distributed in endemic communities to cut off the transmission of NTDs including schistosomiasis.Praziquantel is the sole drug for the treatment of all forms of Schistosomiasis currently and it has been proven to be highly efficacious. The WHO’s Preventative chemotherapy program uses the same drug as a prophylactic tool to control the disease.This drug presents a challenge in administering it to younger school children due to its size and the unpleasant taste of the available 600mg tablet. This makes it difficult to administer the correct dosage of the drug to school children and it excludes preschoolers from administration program.This study was done as a swillandspit exercise (the drug was not ingested) to assess the new orally disintegrating isomers of Praziquantel, L-PZQ and Rac-PZQ which have been prepared as 150mg tablets and sweetened through the addition of a sweetener (Sucralose), in comparision to the existing Praziquantel formulation. Findings from 48 African children showed that both new formulations are more palatable to younger children as compared to the existing Praziquantel formulation.These results provided confidence for further evaluation of the clinical efficacy and tolerability of the paediatric friendly formulations of Praziquantel tablets for schistosomiasis treatment.

Background Parents are the primary caregivers of young children. Responsive parent–child relationships and parental support for learning during the earliest years of life are crucial for promoting early child development (ECD). We conducted a global systematic review and meta-analysis to evaluate the effectiveness of parenting interventions on ECD and parenting outcomes. Methods and findings We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Global Health Library for peer-reviewed, published articles from database inception until November 15, 2020. We included randomized controlled trials (RCTs) of parenting interventions delivered during the first 3 years of life that evaluated at least 1 ECD outcome. At least 2 reviewers independently screened, extracted data, and assessed study quality from eligible studies. ECD outcomes included cognitive, language, motor, and socioemotional development, behavior problems, and attachment. Parenting outcomes included parenting knowledge, parenting practices, parent–child interactions, and parental depressive symptoms. We calculated intervention effect sizes as the standardized mean difference (SMD) and estimated pooled effect sizes for each outcome separately using robust variance estimation meta-analytic approaches. We used random-effects meta-regression models to assess potential effect modification by country-income level, child age, intervention content, duration, delivery, setting, and study quality. This review was registered with PROSPERO (CRD42018092458 and CRD42018092461). Of the 11,920 articles identified, we included 111 articles representing 102 unique RCTs. Pooled effect sizes indicated positive benefits of parenting interventions on child cognitive development (SMD = 0.32, 95% CI [confidence interval]: 0.23, 0.40, P < 0.001), language development (SMD = 0.28, 95% CI: 0.18 to 0.37, P < 0.001), motor development (SMD = 0.24, 95% CI: 0.15 to 0.32, P < 0.001), socioemotional development (SMD = 0.19, 95% CI: 0.10 to 0.28, P < 0.001), and attachment (SMD = 0.29, 95% CI: 0.18 to 0.40, P < 0.001) and reductions in behavior problems (SMD = −0.13, 95% CI: −0.18 to −0.08, P < 0.001). Positive benefits were also found on parenting knowledge (SMD = 0.56, 95% CI: 0.33 to 0.79, P < 0.001), parenting practices (SMD = 0.33, 95% CI: 0.22 to 0.44, P < 0.001), and parent–child interactions (SMD = 0.39, 95% CI: 0.24 to 0.53, P < 0.001). However, there was no significant reduction in parental depressive symptoms (SMD = −0.07, 95% CI: −0.16 to 0.02, P = 0.08). Subgroup analyses revealed significantly greater effects on child cognitive, language, and motor development, and parenting practices in low- and middle-income countries compared to high-income countries; and significantly greater effects on child cognitive development, parenting knowledge, parenting practices, and parent–child interactions for programs that focused on responsive caregiving compared to those that did not. On the other hand, there was no clear evidence of effect modification by child age, intervention duration, delivery, setting, or study risk of bias. Study limitations include considerable unexplained heterogeneity, inadequate reporting of intervention content and implementation, and varying quality of evidence in terms of the conduct of trials and robustness of outcome measures used across studies. Conclusions Parenting interventions for children during the first 3 years of life are effective for improving ECD outcomes and enhancing parenting outcomes across low-, middle-, and high-income countries. Increasing implementation of effective and high-quality parenting interventions is needed globally and at scale in order to support parents and enable young children to achieve their full developmental potential., In a systematic review and meta-analysis, Joshua Jeong and colleagues study the effectiveness of parenting interventions in children 3 years and younger in promoting early childhood development and parenting outcomes., Author summary Why was this study done? Parenting interventions have been underscored as a key strategy for improving early child development (ECD) outcomes. Although there are several existing reviews regarding the effectiveness of parenting interventions for improving ECD outcomes, prior reviews have focused narrowly on select types of parenting interventions, evaluated impacts on single ECD domain outcomes, included studies in either only high-income countries (HICs) or low- and middle-income countries (LMICs), and have not adequately explored treatment heterogeneity and potential moderators. What did the researchers do and find? We conducted a systematic review and meta-analysis of 102 randomized controlled trials of parenting interventions for children during the first 3 years of life that were implemented across a total of 33 countries. We found that parenting interventions improved early child cognitive, language, motor, socioemotional development, and attachment and reduced behavior problems. Parenting interventions additionally improved parenting knowledge, parenting practices, and parent–child interactions. However, they did not significantly reduce parental depressive symptoms. We found that parenting interventions had significantly greater effects on child cognitive, language, and motor development and parenting practices in LMICs than HICs (e.g., effect on cognitive development was 3 times greater in LMICs versus HICs). Parenting interventions that included content on responsive caregiving had significantly greater effects on child cognitive development, parenting knowledge, parenting practices, and parent–child interactions than interventions that did not include content on responsive caregiving (e.g., effect on parenting practices was nearly 4 times greater for interventions with responsive caregiving content versus those without responsive caregiving content). We uncovered substantial variation in program content and implementation characteristics across studies and considerable heterogeneity in pooled effect size estimates across nearly all evaluated outcomes. What do these findings mean? To the best of our knowledge, this is the largest and most comprehensive global systematic review and meta-analysis that demonstrates the effectiveness of parenting interventions during the first 3 years of life on a wide range of ECD and parent-level outcomes. Parenting programs are needed globally to enhance parent–child relationships and promote the healthy development of children during the earliest years of life. Future research should unpack the observed variability in program components and implementation features used across parenting interventions and examine their associations with outcomes to inform improved delivery, effectiveness, and scale of parenting interventions for ECD.

Background Depression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda. Methods and findings Between 2016 and 2018, research assistants visited the homes of 1,626 adult residents of Nyakabare Parish, a rural area in southwestern Uganda. ACEs were assessed using a modified version of the Adverse Childhood Experiences-International Questionnaire, and depression symptom severity and suicidal ideation were assessed using the Hopkins Symptom Checklist for Depression (HSCL-D). We applied a validated algorithm to determine major depressive disorder diagnoses. Overall, 1,458 participants (90%) had experienced at least one ACE, 159 participants (10%) met criteria for major depressive disorder, and 28 participants (1.7%) reported suicidal ideation. We fitted regression models to estimate the associations between cumulative number of ACEs and depression symptom severity (linear regression model) and major depressive disorder and suicidal ideation (Poisson regression models). In multivariable regression models adjusted for age, sex, primary school completion, marital status, self-reported HIV status, and household asset wealth, the cumulative number of ACEs was associated with greater depression symptom severity (b = 0.050; 95% confidence interval [CI], 0.039–0.061, p < 0.001) and increased risk for major depressive disorder (adjusted relative risk [ARR] = 1.190; 95% CI, 1.109–1.276; p < 0.001) and suicidal ideation (ARR = 1.146; 95% CI, 1.001–1.311; p = 0.048). We assessed the robustness of our findings by probing for nonlinearities and conducting analyses stratified by age. The limitations of the study include the reliance on retrospective self-report as well as the focus on ACEs that occurred within the household. Conclusions In this whole-population, cross-sectional study of adults in rural Uganda, the cumulative number of ACEs had statistically significant associations with depression symptom severity, major depressive disorder, and suicidal ideation. These findings highlight the importance of developing and implementing policies and programs that safeguard children, promote mental health, and prevent trajectories toward psychosocial disability., In a cross-sectional, population based study of adults in rural Uganda, Emily Satinsky and colleagues investigate adverse childhood experiences and associations with depression and suicidal ideation., Author summary Why was this study done? Depression is recognized globally as a leading cause of disability. Studies from high-income countries have shown robust associations between adverse childhood experiences (ACEs) and depression during adulthood. While studies from sub-Saharan Africa have demonstrated associations between ACEs and depression and suicidality among children, adolescents, and young adults, no study from this region has yet estimated the associations between ACEs and major depressive disorder and suicidal ideation within a whole-population sample of adults. What did the researchers do and find? We conducted a cross-sectional, population-based study of 1,626 adults in rural Uganda, eliciting ACEs, current depression, and suicidal ideation through face-to-face interviews. The cumulative number of ACEs that occurred before age 18 had statistically significant associations with adult depression symptom severity, major depressive disorder, and suicidal ideation. Depression symptom severity and major depressive disorder had statistically significant associations with each of the 9 types of ACEs. Suicidal ideation also had statistically significant associations with living with an adult who was sent to jail or prison during childhood and experiencing food and/or water insecurity during childhood. What do these findings mean? Our interpretation of these findings raises implications for the development of policies and programs that support children, adolescents, and their families, and promote mental health. We are not able to determine the extent to which these associations are causal, and our analysis is susceptible to potential bias from the use of retrospective self-report of ACEs.

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching, Author summary Despite widespread, effective use of ART among HIV infected pregnant women, new pediatric HIV infections increase by about 150,000 every year. Thus, alternative strategies will be required to reduce MTCT and eliminate pediatric HIV infections. Interestingly, in the absence of ART, less than half of HIV-infected pregnant women will transmit HIV, suggesting natural immune protection of infants from virus acquisition. To understand the impact of maternal plasma autologous virus neutralization responses on MTCT, we compared the plasma and bnAb neutralization sensitivity of the circulating viral population present at the time of delivery in untreated, HIV-infected transmitting and non-transmitting mothers. While there was no significant difference in the ability of transmitting and non-transmitting women to neutralize their own circulating virus strains, specific genetic motifs enriched in variants from transmitting mothers were associated with resistance to bnAbs, suggesting that acquired bnAb resistance is a common feature of vertically-transmitted variants. This work suggests that enhancement of plasma neutralization responses in HIV-infected mothers through passive or active vaccination could further drive selection of variants that could be vertically transmitted, and cautions the use of passive bnAbs for HIV-1 prophylaxis or therapy during pregnancy.

ObjectiveParent-mediated programmes have been found to be cost effective for addressing the needs of the children and adolescents with Neurodevelopmental Disorders (NDD) in high-income countries. We explored the impact of parent-mediated intervention programmes in South Asia, where the burden of NDD is high.MethodsA systematic review was conducted using the following databases; PUBMED, MEDLINE, PsycINFO, Google Scholar and Web of Science. Predefined MeSH terms were used, and articles were included if published prior to January 2020. Two independent researchers screened the articles and reviewed data.Outcomes measuresThe review included studies that targeted children and adolescents between 1 and 18 years of age diagnosed with any of four specific NDDs that are commonly reported in South Asia; Autism Spectrum Disorder (ASD), Intellectual Disability (ID), Attention Deficit Hyperactivity Disorder (ADHD) and Cerebral Palsy (CP). Studies that reported on parent or child outcomes, parent-child interaction, parent knowledge of NDDs, or child activities of daily living were included for full text review.ResultsA total of 1585 research articles were retrieved and 23 studies met inclusion criteria, including 9 Randomized Controlled Trials and 14 pre-post intervention studies. Of these, seventeen studies reported effectiveness, and six studies reported feasibility and acceptability of the parent-mediated interventions. Three studies demonstrated improved parent-child interaction, three studies demonstrated improved child communication initiations, five studies reported improved social and communication skills in children, four studies demonstrated improved parental knowledge about how to teach their children, and four studies reported improved motor and cognitive skills, social skills, language development, learning ability, or academic performance in children.ConclusionThis systematic review of 23 studies demonstrated improvements in parent and child skills following parent-mediated intervention in South Asia. Additional evaluations of locally customized parent-mediated programmes are needed to support development of feasible interventions for South Asian countries.

Poor water, sanitation and hygiene (WaSH) conditions are hypothesized to contribute to environmental enteric dysfunction (EED), a subclinical condition that may be associated with chronic undernutrition and impaired linear growth. We evaluated the effect of a combined water and sanitation intervention on biomarkers of EED, and then assessed associations of biomarkers of EED with height-for-age z-scores (HAZ), in children under five. We conducted a sub-study within a matched cohort study of a household-level water and sanitation infrastructure intervention in rural Odisha, India, in which we had observed an effect of the intervention on HAZ. We collected stool samples (N = 471) and anthropometry data (N = 209) for children under age 5. We analyzed stool samples for three biomarkers of EED: myeloperoxidase (MPO), neopterin (NEO), and α1-anti-trypsin (AAT). We used linear mixed models to estimate associations between the intervention and each biomarker of EED and between each biomarker and HAZ. The intervention was inversely associated with AAT (-0.25 log μg/ml, p = 0.025), suggesting a protective effect on EED, but was not associated with MPO or NEO. We observed an inverse association between MPO and HAZ (-0.031 per 1000 ng/ml MPO, p = 0.0090) but no association between either NEO or AAT and HAZ. Our results contribute evidence that a transformative WaSH infrastructure intervention may reduce intestinal permeability, but not intestinal inflammation and immune activation, in young children. Our study also adds to observational evidence of associations between intestinal inflammation and nutritional status, as measured by HAZ, in young children. Trial Registration: ClinicalTrials.gov (NCT02441699)., Author summary Intestinal dysfunction due to mucosal inflammation, known as environmental enteric dysfunction, has been hypothesized to contribute to child undernutrition in low- and middle-income countries. Poor water and sanitation conditions are thought to be an underlying cause of both environmental enteric dysfunction and child undernutrition. To examine these relationships, we conducted a sub-study within a larger matched cohort study of a household-level water and sanitation intervention in rural Odisha, India. We collected stool samples from children under age five years and analyzed them for three biomarkers of environmental enteric dysfunction: myeloperoxidase, neopterin, and α1-anti-trypsin. We also assessed the same children’s nutritional status by measuring their height and calculating their height-for-age z-score. We observed a protective effect of the water and sanitation infrastructure intervention on α1-anti-trypsin. We also observed an association between myeloperoxidase and child height-for-age z-score. Our results contribute evidence that a transformative water and sanitation infrastructure intervention may reduce environmental enteric dysfunction in young children. Our study also adds to observational evidence that intestinal inflammation may be related to chronic undernutrition in young children, though the exact nature and relative importance of that relationship remains unclear.

Although malaria mortality among children under five years of age is high, the characteristics of their infection patterns are not well described. The aim of this study was to examine the longitudinal sequence pattern of Plasmodium falciparum infections in the first year of life within a birth cohort in Kintampo, Ghana (N = 1855). Infants were monitored at home with monthly sampling and also at the clinic for any febrile illness between 2008 and 2011. Light microscopy was performed on monthly scheduled visits and febrile ill visits over twelve months of follow-ups (n = 19231). Microscopy-positive visits accompanied with or without symptoms were rare during the first five months of life but were common from six to twelve months of age. Among 1264 infants with microscopy data over a minimum of eight monthly visits and also throughout in sick visits, some were microscopy negative (36%), and others positive: only-symptomatic (35%), alternating (22%) and only-asymptomatic (7%). The median age of microscopic infection was seven months for the alternating group and eight months for both the only-symptomatic and only-asymptomatic groups. The alternating group had the highest cumulative incidence of microscopic infections, the lowest age at first infection and 87 different infection patterns. Parasite densities detected by microscopy were significantly higher for symptomatic versus asymptomatic infection. We conclude that infants in malaria endemic areas experience diverse infection profiles throughout their first year of life. Further investigations should include submicroscopic reservoir and may shed more light on the factors that determine susceptibility to malaria during infancy.

Background Little is known about factors associated with recovery of kidney function—and return to dialysis independence—or temporal trends in recovery after starting outpatient dialysis in the United States. Understanding the characteristics of individuals who may have the potential to recover kidney function may promote better recognition of such events. The goal of this study was to determine factors associated with recovery of kidney function in children compared with adults starting dialysis in the US. Methods and findings We determined factors associated with recovery of kidney function—defined as survival and discontinuation of dialysis for ≥90-day period—in children versus adults who started maintenance dialysis between 1996 and 2015 according to the United States Renal Data System (USRDS) followed through 2016 in a retrospective cohort study. We also examined temporal trends in recovery rates over the last 2 decades in this cohort. Among 1,968,253 individuals included for study, the mean age was 62.6 ± 15.8 years, and 44% were female. Overall, 4% of adults (83,302/1,953,881) and 4% of children (547/14,372) starting dialysis in the outpatient setting recovered kidney function within 1 year. Among those who recovered, the median time to recovery was 73 days (interquartile range [IQR] 43–131) in adults and 100 days (IQR 56–189) in children. Accounting for the competing risk of death, children were less likely to recover kidney function compared with adults (sub-hazard ratio [sub-HR] 0.81; 95% CI 0.74–0.89, p-value, In a retrospective study, Elaine Ku and colleagues investigate factors associated with recovery of kidney function among adults and children receiving dialysis reported in the United States Renal Data System., Author summary Why was this study done? Factors that predict a high potential for recovery of kidney function in dialysis patients are important to identify so that individuals who have the potential for recovery can be closely followed and their recovery recognized. The aim of this study was to determine the likelihood of recovery of kidney function following the start of maintenance dialysis in children and adults. What did the researchers do and find? We found that 4% of children and adults recovered kidney function after starting dialysis, but children were not more likely to recover kidney function compared with adults. Recovery rates improved initially over time in both children and adults but began to decline around 2010 and varied depending on age, race, and cause of kidney disease. What do these findings mean? Discontinuation of outpatient dialysis due to recovery of kidney function was observed in approximately 4% patients with end-stage kidney disease (ESKD) but was especially common among those with acute tubular necrosis (ATN) or acute interstitial nephritis (AIN) as the cause of their kidney disease. Additional studies are needed to understand how to best recognize and promote recovery in patients whose potential to discontinue dialysis is high in the outpatient setting.

In several nations, caries in pre-school children remain a significant oral health issue. In an outbreak period such as the Coronavirus disease 2019 (COVID-19), remote contact and education aimed at the prevention of oral diseases and the preservation of children’s oral health are more relevant than ever. Currently, the amount of published applications is far higher than the published scientific studies while the problems of usability remains vulnerable. The goal of this paper was to comprehensively document the phase of development and usability testing of a mobile application for diet and oral health, namely Gigiku Sihat, which was primarily intended to be used by parents and guardians of pre-school children. The mobile application was developed using the System Development Life Cycle principle. Apart from searching for the available oral health application on Android platform, the initial requirement gathering process consisted of situational analysis, concept generation, content development, and features and functional requirement determination. The mobile application design and implementation evolved at each phase before being finalised. Gigiku Sihat was successfully developed in the Bahasa Malaysia. Finalised Gigiku Sihat was installed on mobile devices to determine the usability using translated and validated System Usability Scale questionnaire namely Skala Kebolehgunaan Aplikasi Mudah Alih (SKAMA). The mean score usability with score of 68 and above was deemed to have good usability. This study found that Gigiku Sihat mean (SD) usability score was 77.0 (14.18). The results were promising as they showed that Gigiku Sihat had a good usability. Thus, the development of this mobile application focusing on diet and oral health served as a new source of oral health education and provided a necessary foundation in developing future improved mobile application development for parents in the prevention of early childhood caries.

Background Gynaecological morbidities are more common than reproductive and contraceptive morbidities and constitute a substantial proportion of disease burden in women. This study aimed to examine the prevalence and factors associated with gynaecological morbidities and the treatment-seeking behaviour among adolescent girls residing in Bihar and Uttar Pradesh, India. Methodology The study utilized data from the Understanding the Lives of Adolescents and Young Adults (UDAYA) survey with a sample size of 14,625 adolescents girls aged 10–19 years. We defined gynaecological morbidity in dichotomous form, created from five questions on different morbidities. Further, the treatment-seeking behaviour was assessed for reported gynaecological morbidities three months prior to the survey. Univariate and bivariate analysis was used to perform analysis to carve out the preliminary results. Additionally, the study employed the heckprobit selection model, a two-equation model, to identify the determinants of outcome variables. Results Overall, about one-fourth (23.6%) of the adolescent girls reported suffering from gynaecological morbidities, and only one-third of them went for treatment. Non-Scheduled Caste/Scheduled Tribe (Non-SC/ST) adolescents were significantly less likely to have gynaecological morbidities (β: -0.12; CI: -0.18, -0.06) compared to SC/ST counterparts; however, they were more likely to go for the treatment (β: 0.09; CI: 0.00, 0.19). The adolescents who had 8–9 (β: 0.17; CI: 0.05, 0.29) or ten and above years of education (β: 0.21; CI: 0.09, 0.34) had a higher likelihood of going for the treatment than adolescents with no education. Moreover, adolescents who belonged to rural areas were less likely to go for the treatment of gynaecological morbidities (β: -0.09; CI: -0.17, -0.01) than urban counterparts. Conclusion Multi-pronged interventions are the need of the hour to raise awareness about the healthcare-seeking behaviour for gynaecological morbidities, especially in rural areas. Adolescent girls shall be prioritized as they may lack the knowledge for gynaecological morbidities, and such morbidities may go unnoticed for years. Mobile clinics may be used to disseminate appropriate knowledge among adolescents and screen asymptomatic adolescents for any possible gynaecological morbidity.

Background Tunga penetrans, also known as sand flea, causes Tungiasis in humans and animals. Despite its notoriety as an entomological problem, however, the ectoparasite receives little consideration from public health professionals. It is against this background that this article aims to assess the prevalence of and factors associated with Tunga penetrans infestation among 5-14-year-olds in rural Western Ethiopia. Methods From November to December 2020, 487 children aged 5 to 14 were selected from four primary schools in a cross-sectional study using systematic random sampling. Clinical exams, Interviews with parents/guardians and observations of the housing and classroom environments were used to collect data. Descriptive statistics and multivariable regression were used to characterize the data and identify factors associated with Tunga penetrans infestation. Result Tunga penetrans infestation (Tungiasis) was diagnosed in 138 of the 487 children examined, placing the prevalence at 28.3% (95% CI: 24.2%, 32.2%). Mud plastered walls [AOR: 5.83, % CI (3.44–9.88)], having cats in the house [AOR: 5.91, 95% CI (3.51–10.11)], not having separated sleeping quarters for animals [AOR: 4.60, 95% CI (2.69–7.86)], using self-supplied water [AOR: 6.30, 95% CI (3.33–11.93)], walking>30 minutes to school [AOR: 2.37, 95% CI (1.48–3.80)] were associated with Tungiasis. Conclusion In one way or another, several of the identified factors were linked to poverty. Improved house wall materials, fumigation of mud-plastered houses, dusting or spraying insecticides on domestic animals (such as cats), improved access to water, community education about keeping animals separated from living spaces, and hygiene promotion are all needed, with a focus on locally available, low-cost technologies that the poorest families can afford.

Hepatitis A, an acute type of hepatitis caused by the hepatitis A virus, occurs worldwide. Following the 2009 hepatitis A epidemic in South Korea, patient outbreak reports were collectively converted to an “all-patient report” in 2011, and national immunization programs were introduced for children in 2015. In this study, we aimed to analyze the changes and characteristics of hepatitis A antibody titers in South Korea following the epidemic. The results of hepatitis A antibody tests performed at clinical laboratories from 2009 to 2019 were analyzed based on year, age, region, sex, and medical institution. The average 2009–2018 positive anti-hepatitis A virus immunoglobulin G rate was 51.8%, but it increased (56.06%) in 2019. Significantly different antibody-positive rates were observed based on age

Background Access to health services across the continuum of care improves maternal and newborn health outcomes. Ethiopia launched the Community-Based Newborn Care programme in 2013 to increase the coverage of antenatal care, institutional delivery, postnatal care and newborn care. The programme also introduced gentamicin and amoxicillin treatment by health extension workers for young infants with possible serious bacterial infection when referral was not possible. This study aimed to assess the extent to which the coverage of health services for mothers and their young infants increased after the initiation of the programme. Methods A baseline survey was conducted in October-December 2013 and a follow-up survey four years later in November-December 2017. At baseline, 10,224 households and 1,016 women who had a live birth in the 3–15 months prior to the survey were included. In the follow-up survey, 10,270 households and 1,057 women with a recent live birth were included. Women were asked about their experience of care during pregnancy, delivery and postpartum periods, as well as the treatment provided for their child’s illness in the first 59 days of life. Results Between baseline and follow-up surveys the proportion of women reporting at least one antenatal care visit increased by 15 percentage points (95% CI: 10,19), four or more antenatal care visits increased by 17 percentage points (95%CI: 13,22), and institutional delivery increased by 40 percentage points (95% CI: 35,44). In contrast, the proportion of newborns with a postnatal care visit within 48 hours of birth decreased by 6 percentage points (95% CI: -10, -3) for home deliveries and by 14 percentage points (95% CI: -21, -7) for facility deliveries. The proportion of mothers reporting that their young infant with possible serious bacterial infection received amoxicillin for seven days increased by 50 percentage points (95% CI: 37,62) and gentamicin for seven days increased by 15 percentage points (95% CI: 5,25). Concurrent use of both antibiotics increased by 12 percentage points (95% CI: 4,19). Conclusion The Community-Based Newborn Care programme was an ambitious initiative to enhance the access to services for pregnant women and newborns. Major improvements were seen for the number of antenatal care visits and institutional delivery, while postnatal care remained alarmingly low. Antibiotic treatment for young infants with possible serious bacterial infection increased, although most treatment did not follow national guidelines. Improving postnatal care coverage and using a simplified antibiotic regimen following recent World Health Organization guidelines could address gaps in the care provided for sick young infants.

Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1β, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16–2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985–1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.

Allergic rhino-conjunctivitis with pollen allergy has been prevalent worldwide and Pollen-food allergy syndrome (PFAS) refers to individuals with pollen allergy who develop oral allergy syndrome (OAS) on consuming fruits and vegetables. The prevalence of PFAS varies by region and that in Japanese adolescents remains to be elucidated. In this cross-sectional study, we examined the epidemiological characteristics of PFAS in a general population of Japanese adolescents according to pollen allergy, OAS, and IgE component sensitization. Participants comprised adolescents, at age 13 years, from a prospective birth cohort study in Japan. We administered questionnaires to collect information from parents regarding pollen allergy, PFAS and OAS at each child’s age 13 years. ImmunoCAP ISAC was used to assess IgE component sensitization. Among 506 participants with a complete questionnaire and ISAC measurement results, 56.5% had a history of hay fever, 16.0% had a history of OAS, 51.0% had pollen allergy, and 11.7% had a history of PFAS; additionally, 72.7% were sensitized to one or more tree, grass, and/or weed allergens. The most common sensitization (95.7%) among adolescents with pollen allergy was to Japanese cedar (Cry j 1). The most common causal foods were kiwi and pineapple (both 39.0%). Knowledge levels about PFAS were poor among affected adolescents. We found a high prevalence of PFAS among adolescents in Japan. Although it affects approximately 1/10 adolescents in the general population, public awareness regarding PFAS is poor. Interventional strategies are needed to increase knowledge and to prevent PFAS in the general population.

Background Pediatric SARS-CoV-2 data remain limited and seropositivity rates in children were reported as Methods Children and adolescents ≤19 years were enrolled in a cross-sectional, observational study of SARS-CoV-2 seroprevalence from July-October 2020 in Northern Virginia, US. Demographic, health, and COVID-19 exposure information was collected, and blood analyzed for SARS-CoV-2 spike protein total antibody. Risk factors associated with SARS-CoV-2 seropositivity were analyzed. Orthogonal antibody testing was performed, and samples were evaluated for responses to different antigens. Results In 1038 children, the anti-SARS-CoV-2 total antibody positivity rate was 8.5%. After multivariate logistic regression, significant risk factors included Hispanic ethnicity, public or absent insurance, a history of COVID-19 symptoms, exposure to person with COVID-19, a household member positive for SARS-CoV-2 and multi-family or apartment dwelling without a private entrance. 66% of seropositive children had no symptoms of COVID-19. Secondary analysis included orthogonal antibody testing with assays for 1) a receptor binding domain specific antigen and 2) a nucleocapsid specific antigen had concordance rates of 80.5% and 79.3% respectively. Conclusions A much higher burden of SARS-CoV-2 infection, as determined by seropositivity, was found in children than previously reported; this was also higher compared to adults in the same region at a similar time. Contrary to prior reports, we determined children shoulder a significant burden of COVID-19 infection. The role of children’s disease transmission must be considered in COVID-19 mitigation strategies including vaccination.

Background Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. Objective Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. Methods Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007–2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. Results Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. Conclusions Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

Purpose Pre-exposure prophylaxis for HIV (PrEP) is an effective yet underutilized biomedical tool for adolescents and young adults’ (AYA) HIV prevention due to barriers such as PrEP adherence. We assessed HIV prevention knowledge, attitudes and beliefs from adults who self-identified as a primary support person to an AYA. Methods We surveyed AYA primary support persons at an academic hospital. Univariate and multivariate regression analyses were completed to identify factors associated with the belief AYAs engaging in HIV-associated behaviors should use PrEP and willingness to support AYAs on PrEP. Results 200 primary support persons completed the survey. Participants were predominately female (77%) and black (56%). Nearly all primary support persons believed AYAs engaging in HIV-associated behaviors should take PrEP (94%) and 98% would support an AYA taking PrEP via transportation to appointments, assistance with refilling prescriptions, medication reminders, or encouragement. Conclusions Primary support persons are willing to support AYAs using PrEP.

Objective In the present study, we aimed to evaluate the virological failure (VF) and drug resistance among treated HIV-infected children after five years follow-up in the ANRS-Pediacam cohort in Cameroon. Methods From November 2007 to October 2011, HIV-infected children born to HIV-infected mothers were included in the ANRS-PEDIACAM study and followed-up for more than 5 years. Plasma viral load (VL) was measured at each visit (every three months until month 24 and every 6 months thereafter). VF was the main outcome and HIV drug resistance test was performed using the ANRS procedures and algorithm. Results Data from 155 children were analyzed. The median age at combination antiretroviral therapy (cART) initiation was 4.2 months (interquartile range (IQR): 3.2–5.8), with 103 (66.5%) children taking LPV/r-containing regimen and 51 (32.9%) children taking NVP. After five years follow-up, 63 (40.6%; CI: 32.9–48.8) children experienced VF. The median duration between cART initiation and VF was 22.1 months (IQR: 11.9–37.1) with a median VL of 4.8 log10 (IQR: 4.0–5.5). Among the 57 children with HIV drug resistance results, 40 (70.2%) had at least one drug resistance mutation. The highest resistance rates (30.4–66.1%) were obtained with Lamivudine; Efavirenz; Nevirapine and Rilpivirine. Conclusions These results show high resistance to NNRTI and emphasize the need of VL and resistance tests for optimal follow-up of HIV-infected people especially children.

BackgroundVitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency.MethodsFrom 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence.ResultsAt study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70–4.08) and 0.25 (95% CI 0.21–0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04–19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants.ConclusionARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting.

Studies on sugar-sweetened beverage consumption patterns can help in the individual and population level management of chronic non-communicable diseases and other conditions. This study aimed to identify the association between health behavior patterns and the consumption of sugar-sweetened beverages among Brazilian adolescents from a nationally representative school-based study. A cross-sectional study analyzed data from 71,553 adolescents aged 12–17 years who attended public and private schools in Brazilian cities, from the Study of Cardiovascular Risk in Adolescents. Principal component analysis was performed to identify health behavior patterns, and ordered logistic regression was performed to identify the association between health behavior patterns and sugar-sweetened beverage consumption. Sugar-sweetened beverage consumption (mL/day) was used as the dependent variable. The analyses were performed using Stata software version 14.0 with a significance level of 0.05. Patterns 2 (alcoholic beverage and smoking habit) and 3 (ultra-processed food and screen time) of health behaviors and regularly purchasing snacks in the school cafeteria increased the odds of sugar-sweetened beverage consumption, while pattern 1 (water, unprocessed and minimally processed food and physical activity) decreased these odds. The adoption of healthy habits can indirectly stimulate the adoption of other habits beneficial to health. These results indicate the importance of adopting a set of regulatory measures to reduce sugar-sweetened beverage consumption.

ObjectiveTo determine 1-year attributable healthcare costs of bronchiolitis.MethodsUsing a population-based matched cohort and incidence-based cost analysis approach, we identified infants ResultsWe identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148–4,477), with $2,847 (95%CI: $2,712–2,982) spent on hospitalizations, $610 (95%CI: $594–627) on physician services, $562 (95%CI: $556–567)] on ED visits, $259 (95%CI: $222–297) on other healthcare costs and $35 ($27–42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735–2,794) vs $111 (95%CI: $102–121) in the initial 10 days post index date, $4,695 (95%CI: $4,589–4,800) vs $910 (95%CI: $847–973) in the initial 180 days and $1,158 (95%CI: $1,104–1213) vs $639 (95%CI: $599–679) during days 181–360.Mean 1-year bronchiolitis costs were higher in infants ConclusionsCompared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization.

Background This systematic review described the association between electronic nicotine delivery systems and electronic non-nicotine delivery systems (ENDS/ENNDS) use among non-smoking children and adolescents aged Methods We searched five electronic databases and the grey literature up to end of September 2020. Prospective longitudinal studies that described the association between ENDS/ENNDS use, and subsequent tobacco use in those aged < 20 years who were non-smokers at baseline were included. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess risk of bias. Data were extracted by two reviewers and pooled using a random-effects meta-analysis. We generated unadjusted and adjusted risk ratios (ARRs) describing associations between ENDS/ENNDS and tobacco use. Findings A total of 36 publications met the eligibility criteria, of which 25 were included in the systematic review (23 in the meta-analysis) after exclusion of overlapping studies. Sixteen studies had high to moderate risk of bias. Ever users of ENDS/ENNDS had over three times the risk of ever cigarette use (ARR 3·01 (95% CI: 2·37, 3·82; p2: 82·3%), and current cigarette use had over two times the risk (ARR 2·56 (95% CI: 1·61, 4·07; p2: 77·3%) at follow up. Among current ENDS/ENNDS users, there was a significant association with ever (ARR 2·63 (95% CI: 1·94, 3·57; p2: 21·2%)), but not current cigarette use (ARR 1·88 (95% CI: 0·34, 10·30; p = 0·47, I2: 0%)) at follow up. For other tobacco use, ARR ranged between 1·55 (95% CI 1·07, 2·23) and 8·32 (95% CI: 1·20, 57·04) for waterpipe and pipes, respectively. Additionally, two studies examined the use of ENNDS (non-nicotine devices) and found a pooled adjusted RR of 2·56 (95% CI: 0·47, 13·94, p = 0.035). Conclusion There is an urgent need for policies that regulate the availability, accessibility, and marketing of ENDS/ENNDS to children and adolescents. Governments should also consider adopting policies to prevent ENDS/ENNDS uptake and use in children and adolescents, up to and including a ban for this group.

Introduction Routine viral load (VL) testing among persons living with Human Immunodeficiency Virus (PLHIV) enables earlier detection of sub-optimal antiretroviral therapy (ART) adherence and for appropriate management of treatment failure. Since adoption of this policy by Zimbabwe in 2016, the extent of implementation is unclear. Therefore we set out to determine among PLHIV ever enrolled on ART from 2004–2017 and in ART care for ≥12 months at health facilities providing ART in Zimbabwe: numbers (proportions) with VL testing uptake, VL suppression and subsequently switched to 2nd-line ART following confirmed virologic failure. Materials and methods We used retrospective data from the electronic Patient Monitoring System (ePMS) in which PLHIV on ART are registered at 525 public and 4 private health facilities. Results Among the 392,832 PLHIV in ART care for ≥12 months, 99,721 (25.4%) had an initial VL test done and results available of whom 81,932 (82%) were virally suppressed. Among those with a VL>1000 copies/mL; 6,689 (37.2%) had a follow-up VL test and 4,086 (61%) had unsuppressed VLs of whom only 1,749 (42.8%) were switched to 2nd-line ART. Lower age particularly adolescents (10–19 years) were more likely (ARR 1.34; 95%CI: 1.25–1.44) to have virologic failure. Conclusion The study findings provide insights to implementation gaps including limitations in VL testing; low identification of high- risk PLHIV in care and lack of prompt utilization of test results. The use of electronic patient-level data has demonstrated its usefulness in assessing the performance of the national VL testing program. By end of 2017 implementation of VL testing was sub-optimal, and virological failure was relatively common, particularly among adolescents. Of concern is evidence of failure to act on VL test results that were received. A quality improvement initiative has been planned in response to these findings and its effect on patient management will be monitored.

The objective of this systematic review was to evaluate the association between a soy-based infant diet and the onset of puberty. We included studies in which children were fed a soy-based diet, and we compared them with those who were not. The primary outcomes were the onset of puberty in girls (thelarche, pubarche, and menarche age), boys (pubarche, voice change, testicular and penis enlargement age), and both (risk of delayed and precocious puberty [PP]). Search strategies were performed in PubMed, Embase, LILACS, and CENTRAL databases. Two reviewers selected eligible studies, assessed the risk of bias, and extracted data from the included studies. The odds ratio (OR) and mean difference (MD) were calculated with a 95% confidence interval (CI) as a measure of the association between soy consumption and outcomes. We used a random-effects model to pool results across studies and the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the certainty of evidence. We included eight studies in which 598 children consumed a soy-based diet but 2957 did not. The primary outcomes that could be plotted in the meta-analysis were the risk of PP and age at menarche. There was no statistical difference between groups for PP (OR: 0.51, 95% CI: 0.09 to 2.94, 3 studies, 206 participants, low certainty of evidence). No between-group difference was observed in menarche age (MD 0.14 years, 95% CI -0.16 to 0.45, 3 studies, 605 children, low certainty of evidence). One study presented this outcome in terms of median and interquartile range, and although the onset of menarche was marginally increased in girls who received a soy-based diet, the reported age was within the normal age range for menarche. We did not find any association between a soy-based infant diet and the onset of puberty in boys or girls. Trial Registration: PROSPERO registration: CRD42018088902.

Diagnostic investigation can be carried out using non-radiological and non-contact methods. Moiré topography (MT) seems to be a viable alternative to radiographic research in evaluating the spine and/or trunk deviations. The aim of this systematic review was to analyze the current knowledge regarding the reliability and validity of Moiré topography as a screening and diagnostic tool. The systematic review was performed from 2010 until March 2021 in the PubMed, EBSCO, Web of Science, and Scopus databases, according to the eligibility criteria. This review fulfilled the following criteria according to the PICO system: population (children and adolescents), intervention (MT measurement), comparison (repeated MT measurements, MT compared to Cobb angle or scoliometer), outcome (reliability and validity of MT). Eight studies fulfilled the inclusion criteria for further analysis. All the studies were assessed to be of high quality. Included studies found that MT had high repeatability and high intraobserver and interobserver correlation, and correlation between MT parameters and radiographic Cobb angle ranged from moderate to high. The authors reported difficulty in defining the cut-off values for MT parameter (Surface Trunk Rotation—STR), and unsatisfactory sensitivity and specificity of MT examination. The studies did not reveal the advantage of MT as a screening method in the detection of idiopathic scoliosis in comparison to radiograph. Based on the evidence from eight studies, the results indicated moderate evidence for reliability and validity of Moiré topography as a screening and diagnostic tool. There is still no strong evidence for the accuracy of MT.

Background Cow milk is an important source of macro-and micronutrients. However, it has low iron content but high content of casein and calcium thus could negatively influence hemoglobin synthesis. On the other hand, camel milk contains higher iron concentration than cow milk. In addition, the majority of iron in camel milk is associated with the lower molecular fraction of casein suggesting better bioavailability. Furthermore, vitamin C concentration, a useful iron absorption enhancer, is more than three-fold greater in camel milk than cow milk. This study compared hemoglobin concentration among young children consuming consistently cow milk or camel milk. Methods Hemoglobin concentration of young children (aged 6–59 mo) from settled pastoralist communities of the Somali region, Ethiopia, consistently consuming cow milk (n = 166) or camel milk (n = 166) was determined. In addition, socio-demographic and water, sanitation, and hygienic (WASH) conditions of study participants’ households were captured. Furthermore, dietary intake and anthropometric characteristics of participating children were assessed. Results Among the participating children, 38.6% were underweight, 33.4% were stunted, and 34.5% were wasted. In addition, 77.4% of children were anemic. The present study households had poor WASH conditions. Only 0.6% of children had the minimum acceptable dietary diversity. There was small but significant mean hemoglobin difference among camel milk and cow milk consuming children (9.6±1.8 g/dl vs 9.1±2.2 g/dl; p = 0.012). In addition, the odds of low hemoglobin concentration was greater among cow milk consuming children than camel milk consuming children [AOR 2.17; 95 CI; 1.39, 3.37; p = 0.001]. However, the overall anemia prevalence among the two groups was similar. Conclusion Camel milk consumption is associated with better hemoglobin concentration but may not be sufficient to prevent anemia in populations from resource poor settings. The etiology of anemia is multifactorial thus further studies on the link between milk consumption and hemoglobin concentration are important.

Introduction Addressing the problem of suicidal thoughts and behavior (STB) in adolescents requires understanding the associated risk factors. While previous research has identified individual risk and protective factors associated with many adolescent social morbidities, modern machine learning approaches can help identify risk and protective factors that interact (group) to provide predictive power for STB. This study aims to develop a prediction algorithm for STB among adolescents using the risk and protective factor framework and social determinants of health. Methods The sample population consisted of more than 179,000 high school students living in Utah and participating in the Communities That Care (CTC) Youth Survey from 2011-2017. The dataset includes responses to 300+ questions from the CTC and 8000+ demographic factors from the American Census Survey for a total of 1.2 billion values. Machine learning techniques were employed to extract the survey questions that were best able to predict answers indicative of STB, using recent work in interpretable machine learning. Results Analysis showed strong predictive power, with the ability to predict individuals with STB with 91% accuracy. After extracting the top ten questions that most affected model predictions, questions fell into four main categories: familial life, drug consumption, demographics, and peer acceptance at school. Conclusions Modern machine learning approaches provide new methods for understanding the interaction between root causes and outcomes, such as STB. The model developed in this study showed significant improvement in predictive accuracy compared to previous research. Results indicate that certain risk and protective factors, such as adolescents being threatened or harassed through digital media or bullied at school, and exposure or involvement in serious arguments and yelling at home are the leading predictors of STB and can help narrow and reaffirm priority prevention programming and areas of focused policymaking.

Background Social support and relevant skills training can reduce the risk of postpartum depression (PPD) by reducing the impact of stressors. The 10-step program to encourage exclusive breastfeeding that forms the basis of the Baby-Friendly Hospital Initiative (BFHI) provides both, suggesting it may lessen depressive symptoms directly or by reducing difficulties associated with infant feeding. Our objective was to quantify the association of implementing Steps 1–9 or Steps 1–10 on postpartum depressive symptoms and test whether this association was mediated by breastfeeding difficulties. Methods and findings We used data from a breastfeeding promotion trial of all women who gave birth to a healthy singleton between May 24 and August 25, 2012 in 1 of the 6 facilities comparing different BFHI implementations (Steps 1–9, Steps 1–10) to the standard of care (SOC) randomized by facility in Kinshasa, Democratic Republic of Congo. Depressive symptoms, a non-registered trial outcome, was assessed at 14 weeks via the Edinburgh Postnatal Depression Scale (EPDS). Inverse probability weighting (IPW) was used to estimate the association of BFHI implementations on depressive symptoms and the controlled direct association through breastfeeding difficulties at 10 weeks postpartum. A total of 903 mother–infant pairs were included in the analysis. Most women enrolled had previously given birth (76%) and exclusively breastfed at 10 weeks (55%). The median age was 27 (interquartile range (IQR): 23, 32 years). The proportion of women reporting breastfeeding difficulties at week 10 was higher in both Steps 1–9 (75%) and Steps 1–10 (91%) relative to the SOC (67%). However, the number of reported difficulties was similar between Steps 1–9 (median: 2; IQR: 0, 3) and SOC (2; IQR: 0, 3), with slightly more in Steps 1–10 (2; IQR: 1, 3). The prevalence of symptoms consistent with probable depression (EPDS score >13) was 18% for SOC, 11% for Steps 1–9 (prevalence difference [PD] = −0.08; 95% confidence interval (CI): −0.14 to −0.01, p = 0.019), and 8% for Steps 1–10 (PD = −0.11, −0.16 to −0.05; p < 0.001). We found mediation by breastfeeding difficulties. In the presence of any difficulties, the PD was reduced for both Steps 1–9 (−0.15; 95% confidence level (CL): −0.25, −0.06; p < 0.01) and Steps 1–10 (−0.16; 95% CL: −0.25, −0.06; p < 0.01). If no breastfeeding difficulties occurred in the population, there was no difference in the prevalence of probable depression for Steps 1–9 (0.21; 95% CL: −0.24, 0.66; p = 0.365) and Steps 1–10 (−0.03; 95% CL: −0.19, 0.13; p = 0.735). However, a limitation of the study is that the results are based on 2 hospitals randomized to each group. Conclusions In conclusion, in this cohort, the implementation of the BFHI steps was associated with a reduction in depressive symptoms in the groups implementing BFHI Steps 1–9 or 1–10 relative to the SOC, with the implementation of Steps 1–10 associated with the largest decrease. Specifically, the reduction in depressive symptoms was observed for women reporting breastfeeding difficulties. PPD has a negative impact on the mother, her partner, and the baby, with long-lasting consequences. This additional benefit of BFHI steps suggests that renewed effort to scale its implementation globally may be beneficial to mitigate the negative impacts of PPD on the mother, her partner, and the baby. Trial registration ClinicalTrials.gov NCT01428232, In a cohort study, Robert Agler and colleagues investigate the associations between postnatal depression symptoms and implementation of a Baby-Friendly Hospital Initiative in Kinshasa, Democratic Republic of Congo., Author summary Why was this study done? Depression is common in the postpartum period. Untreated, postpartum depression (PPD) has substantial negative impact on the mother, her partner, and the baby, with long-lasting consequences. Social support and relevant skills training can reduce the risk of PPD by reducing the impact of stressors. The 10-step program to encourage exclusive breastfeeding that forms the basis of the Baby-Friendly Hospital Initiative (BFHI) provides both, but its effect on depression symptoms in postpartum period has not been evaluated. What did the researchers do and find? We found that depressive symptoms were reduced in the groups implementing BFHI Steps 1–9 or 1–10 relative to the standard of care (SOC), with the implementation of Steps 1–10 associated with the largest decrease. The reduction in depressive symptoms associated with the implementation of BHFI Steps 1–9 or Steps 1–10 was observed for women reporting breastfeeding difficulties, but not for women reporting no difficulties. What do these findings mean? Our results suggest that the implementation of the BFHI was associated with a reduction in maternal depressive symptoms and that breastfeeding difficulties play a role in this relationship.

To date no study has examined time trends in adolescent consumption of sugar-sweetened beverages and energy drinks, or modelled change in inequalities over time. The present study aimed to fill this gap by identifying historical trends among secondary school students in Wales, United Kingdom. The present study includes 11–16 year olds who completed the Health Behaviour in School-aged Children (HBSC) survey and the Welsh School Health Research Network (SHRN) survey between 1998 to 2017. Multinomial regression models were employed alongside tests for interaction effects. A total of 176,094 student responses were assessed. From 1998 to 2017, the prevalence of daily sugar-sweetened beverage consumption decreased (57% to 18%) while weekly consumption has remained constant since 2006 (49% to 52%). From 2013 to 2017, daily consumption of energy drinks remained stable (6%) while weekly consumption reports steadily decreased (23% to 15%). Boys, older children and those from a low socioeconomic group reported higher consumption rates of sugar-sweetened beverages and energy drinks. Consumption according to socioeconomic group was the only characteristic to show a statistically significant change over time, revealing a widening disparity between sugar-sweetened beverage consumption rates of those from low and high socioeconomic groups. Findings indicate a positive shift in overall consumption rates of both sugar-sweetened beverages and energy drinks. Adolescents from a low socioeconomic group however were consistently shown to report unfavourable sugar-sweetened beverages consumption when compared to peers from high socioeconomic group. Given the established longer term impacts of sugar-sweetened beverage and energy drink consumption on adolescent health outcomes, urgent policy action is required to reduce overall consumption rates, with close attention to equity of impact throughout policy design and evaluation plans.

Introduction Our aim was to examine attitudes of the general population towards reasonableness of these costs, as well as the degree to which these costs are shared across society (solidarity financing) and to determine the factors associated with them. Method Repeated cross-sectional data from a nationally representative online-survey. More precisely, data from wave 8 (21–22 April 2020) and wave 16 (7–8 July 2020) were used (in wave 8: analytical sample with n = 976, average age was 47.0 years (SD: 15.3 years), ranging from 18 to 74 years, 51.8% female; in wave 16: analytical sample with n = 978, average age was 46.1 years (SD: 15.9 years), ranging from 18 to 74 years, 50.9% female). After a short introduction emphasizing considerable economic costs associated with the measures against the spread of the coronavirus, individuals were asked to rate the following statements (outcome measures), in each case from 1 = strongly disagree to 7 = strongly agree: “These economic costs are currently reasonable in relation to the objective pursued” (reasonableness of costs), “These economic costs should be borne jointly by all citizens and depending on income” (solidarity financing). Results In wave 8 (wave 16 in parentheses), the average rating for the attitude towards reasonableness of costs was 4.3, SD: 1.8 (wave 16, average: 4.2, SD: 1.8) and the average rating for the attitude towards solidarity financing was 3.7, SD: 1.9 (wave 16, average: 3.3, SD: 2.0). In wave 8, more positive attitudes towards the reasonableness of costs and solidarity financing were associated with being male, higher education, not being in a partnership/being unmarried, higher affect regarding COVID-19 and higher presumed severity with respect to COVID-19. Furthermore, more positive attitudes towards the reasonableness of costs were associated with having a migration background. More positive attitudes towards solidarity financing was associated with higher age groups. Mainly similar findings were observed in wave 16. Discussion Agreement with reasonableness of costs of preventative measures as well as solidarity financing was moderately high. Knowledge of these attitudes is important to ensure social cohesion during the fight against COVID-19.

Introduction The SARS-CoV-2 coronavirus pandemic may cause significant morbidity and mortality in adults, yet severe cases are rare among children. The indirect impact of the pandemic on health care delivery in general and pediatric emergency department (PED) visits in particular has been widely reported. Aims To assess the impact of the pandemic and the social restrictions imposed in its wake on PED visits and hospitalization rates in our Israeli medical center. We also sought to track these data in relation to the variation in pandemic severity and social restrictions over time. A comparison of this data with that of the adult emergency department was also performed. Methods Data for this study were drawn from the Shaare Zedek Medical Center (SZMC), Jerusalem, Israel computerized databank. The daily number of PED and adult ER visits as well as hospitalizations resulting from these visits during the months January-July during the years 2018, 2019, 2020 were recorded. We compared the risk ratio for hospitalization in 2019 and 2020, as well as the incidence rate ratio. Results During March and April there was a decrease in PED visits from 4,588 visits in 2019 to 2,527 visits in 2020 (ratio = .551, 95%CI [.52,.58]. Despite the drop in PED visits, the rate of hospitalizations rose with respect to 2019 (Risk Ratio = 1.31, p < .001, 95%CI [1.17,1.47]). Similar but more moderate trends were seen in the adult ED. From May-July 2020, after the lockdown was lifted, PED visits remained 30% below the same time period from 2018 and 2019, while the hospitalization rate returned to its pre-pandemic level. Conclusions A significant drop in PED visits is seen to extend well beyond the peak of the pandemic and the lockdown period. This highlights the potential risk of children with serious emergencies becoming casualties of the pandemic by their not being brought to medical attention. Efforts should be made to raise public awareness among parents and other caretakers of children regarding this matter.

It is essential to equip adolescents with the right information and appropriate skills for a quality transition to their adulthood. This study examines the individual agency of unmarried adolescent girls and young women (AGYW) who were organized into self-help groups (SHG) as compared to those who were not in groups. The paper uses data from a cross-sectional survey conducted with 872 unmarried AGYW aged 15–21 years from 80 villages across two districts of Uttar Pradesh, India. The dependent variables were AGYW’s financial independence, collective action, decisionmaking, mobility, self-expression, generalized perceived self-efficacy, gender norms attitudes, and attitudes toward violence. The primary independent variables were group membership and the duration of the membership. Bivariate and multiple logistic regression analyses were conducted to examine the relationship between group membership and various components of individual agency. More than half of the respondents, with an average age of 18 years were enrolled in school or college and one-third had 12 or more years of education. The group members, compared to non-members, were significantly more likely to be financially independent (odds ratio [OR] = 2.29, p