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Background: The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development.Methods and Findings: The present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y), followed by South Asia (27.7 million; 37.7%) and the East Asia and Pacific region (15.1 million; 25.9%). Positive associations were found between low development scores and stunting, poverty, male sex, rural residence, and lack of cognitive stimulation. Additional research using more detailed developmental assessments across a larger number of LMICs is needed to address the limitations of the present study.Conclusions: The number of children globally failing to reach their developmental potential remains large. Additional research is needed to identify the specific causes of poor developmental outcomes in diverse settings, as well as potential context-specific interventions that might promote children's early cognitive and socioemotional well-being. [ABSTRACT FROM AUTHOR]

Background: Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown.Methods and Findings: PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and the Cochrane database were systematically searched (from database inception to 26 February 2019). Outcomes of GDM-affected pregnancies randomised to treatment with metformin versus insulin were included (randomised controlled trials and prospective randomised controlled studies) from cohorts including European, American, Asian, Australian, and African women. Studies including pregnant women with pre-existing diabetes or non-diabetic women were excluded, as were trials comparing metformin treatment with oral glucose-lowering agents other than insulin. Two reviewers independently assessed articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Outcome measures were parameters of fetal, infant, and childhood growth, including weight, height, BMI, and body composition. In total, 28 studies (n = 3,976 participants) met eligibility criteria and were included in the meta-analysis. No studies reported fetal growth parameters; 19 studies (n = 3,723 neonates) reported measures of neonatal growth. Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7, I2 = 83%, p = 0.005) and lower ponderal indices (mean difference -0.13 kg/m3, 95% CI -0.26 to 0.00, I2 = 0%, p = 0.04) than neonates of insulin-treated mothers. The odds of macrosomia (odds ratio [OR] 0.59, 95% CI 0.46 to 0.77, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99, p = 0.04) were lower following maternal treatment with metformin compared to insulin. There was no difference in neonatal height or incidence of small for gestational age between groups. Two studies (n = 411 infants) reported measures of infant growth (18-24 months of age). In contrast to the neonatal phase, metformin-exposed infants were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830, I2 = 4%, p = 0.03). Three studies (n = 520 children) reported mid-childhood growth parameters (5-9 years). In mid-childhood, BMI was significantly higher (mean difference 0.78 kg/m2, 95% CI 0.23 to 1.33, I2 = 7%, p = 0.005) following metformin exposure than following insulin exposure, although the difference in absolute weights between the groups was not significantly different (p = 0.09). Limited evidence (1 study with data treated as 2 cohorts) suggested that adiposity indices (abdominal [p = 0.02] and visceral [p = 0.03] fat volumes) may be higher in children born to metformin-treated compared to insulin-treated mothers. Study limitations include heterogeneity in metformin dosing, heterogeneity in diagnostic criteria for GDM, and the scarcity of reporting of childhood outcomes.Conclusions: Following intrauterine exposure to metformin for treatment of maternal GDM, neonates are significantly smaller than neonates whose mothers were treated with insulin during pregnancy. Despite lower average birth weight, metformin-exposed children appear to experience accelerated postnatal growth, resulting in heavier infants and higher BMI by mid-childhood compared to children whose mothers were treated with insulin. Such patterns of low birth weight and postnatal catch-up growth have been reported to be associated with adverse long-term cardio-metabolic outcomes. This suggests a need for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure. This review protocol was registered with PROSPERO under registration number CRD42018117503. [ABSTRACT FROM AUTHOR]

Background: Despite the sharp decline in global under-5 deaths since 1990, uneven progress has been achieved across and within countries. In sub-Saharan Africa (SSA), the Millennium Development Goals (MDGs) for child mortality were met only by a few countries. Valid concerns exist as to whether the region would meet new Sustainable Development Goals (SDGs) for under-5 mortality. We therefore examine further sources of variation by assessing age patterns, trends, and forecasts of mortality rates.Methods and Findings: Data came from 106 nationally representative Demographic and Health Surveys (DHSs) with full birth histories from 31 SSA countries from 1990 to 2017 (a total of 524 country-years of data). We assessed the distribution of age at death through the following new demographic analyses. First, we used a direct method and full birth histories to estimate under-5 mortality rates (U5MRs) on a monthly basis. Second, we smoothed raw estimates of death rates by age and time by using a two-dimensional P-Spline approach. Third, a variant of the Lee-Carter (LC) model, designed for populations with limited data, was used to fit and forecast age profiles of mortality. We used mortality estimates from the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) to adjust, validate, and minimize the risk of bias in survival, truncation, and recall in mortality estimation. Our mortality model revealed substantive declines of death rates at every age in most countries but with notable differences in the age patterns over time. U5MRs declined from 3.3% (annual rate of reduction [ARR] 0.1%) in Lesotho to 76.4% (ARR 5.2%) in Malawi, and the pace of decline was faster on average (ARR 3.2%) than that observed for infant (IMRs) (ARR 2.7%) and neonatal (NMRs) (ARR 2.0%) mortality rates. We predict that 5 countries (Kenya, Rwanda, Senegal, Tanzania, and Uganda) are on track to achieve the under-5 sustainable development target by 2030 (25 deaths per 1,000 live births), but only Rwanda and Tanzania would meet both the neonatal (12 deaths per 1,000 live births) and under-5 targets simultaneously. Our predicted NMRs and U5MRs were in line with those estimated by the UN IGME by 2030 and 2050 (they overlapped in 27/31 countries for NMRs and 22 for U5MRs) and by the Institute for Health Metrics and Evaluation (IHME) by 2030 (26/31 and 23/31, respectively). This study has a number of limitations, including poor data quality issues that reflected bias in the report of births and deaths, preventing reliable estimates and predictions from a few countries.Conclusions: To our knowledge, this study is the first to combine full birth histories and mortality estimates from external reliable sources to model age patterns of under-5 mortality across time in SSA. We demonstrate that countries with a rapid pace of mortality reduction (ARR ≥ 3.2%) across ages would be more likely to achieve the SDG mortality targets. However, the lower pace of neonatal mortality reduction would prevent most countries from achieving those targets: 2 countries would reach them by 2030, 13 between 2030 and 2050, and 13 after 2050. [ABSTRACT FROM AUTHOR]

Background: Most of the epidemiological studies that have examined the detrimental effects of ambient hot and cold temperatures on human health have been conducted in high-income countries. In India, the limited evidence on temperature and health risks has focused mostly on the effects of heat waves and has mostly been from small scale studies. Here, we quantify heat and cold effects on mortality in India using a nationally representative study of the causes of death and daily temperature data for 2001-2013.Methods and Findings: We applied distributed-lag nonlinear models with case-crossover models to assess the effects of heat and cold on all medical causes of death for all ages from birth (n = 411,613) as well as on stroke (n = 19,753), ischaemic heart disease (IHD) (n = 40,003), and respiratory diseases (n = 23,595) among adults aged 30-69. We calculated the attributable risk fractions by mortality cause for extremely cold (0.4 to 13.8°C), moderately cold (13.8°C to cause-specific minimum mortality temperatures), moderately hot (cause-specific minimum mortality temperatures to 34.2°C), and extremely hot temperatures (34.2 to 39.7°C). We further calculated the temperature-attributable deaths using the United Nations' death estimates for India in 2015. Mortality from all medical causes, stroke, and respiratory diseases showed excess risks at moderately cold temperature and hot temperature. For all examined causes, moderately cold temperature was estimated to have higher attributable risks (6.3% [95% empirical confidence interval (eCI) 1.1 to 11.1] for all medical deaths, 27.2% [11.4 to 40.2] for stroke, 9.7% [3.7 to 15.3] for IHD, and 6.5% [3.5 to 9.2] for respiratory diseases) than extremely cold, moderately hot, and extremely hot temperatures. In 2015, 197,000 (121,000 to 259,000) deaths from stroke, IHD, and respiratory diseases at ages 30-69 years were attributable to moderately cold temperature, which was 12- and 42-fold higher than totals from extremely cold and extremely hot temperature, respectively. The main limitation of this study was the coarse spatial resolution of the temperature data, which may mask microclimate effects.Conclusions: Public health interventions to mitigate temperature effects need to focus not only on extremely hot temperatures but also moderately cold temperatures. Future absolute totals of temperature-related deaths are likely to depend on the large absolute numbers of people exposed to both extremely hot and moderately cold temperatures. Similar large-scale and nationally representative studies are required in other low- and middle-income countries to better understand the impact of future temperature changes on cause-specific mortality. [ABSTRACT FROM AUTHOR]

Background: Poor early childhood development (ECD) in low- and middle-income countries is a major concern. There are calls to universalise access to ECD interventions through integrating them into existing government services but little evidence on the medium- or long-term effects of such scalable models. We previously showed that a psychosocial stimulation (PS) intervention integrated into a cash transfer programme improved Colombian children's cognition, receptive language, and home stimulation. In this follow-up study, we assessed the medium-term impacts of the intervention, 2 years after it ended, on children's cognition, language, school readiness, executive function, and behaviour.Methods and Findings: Study participants were 1,419 children aged 12-24 months at baseline from beneficiary households of the cash transfer programme, living in 96 Colombian towns. The original cluster randomised controlled trial (2009-2011) randomly allocated the towns to control (N = 24, n = 349), PS (N = 24, n = 357), multiple micronutrient (MN) supplementation (N = 24, n = 354), and combined PS and MN (N = 24, n = 359). Interventions lasted 18 months. In this study (26 September 2013 to 11 January 2014), we assessed impacts on cognition, language, school readiness, executive function, and behaviour 2 years after intervention, at ages 4.5-5.5 years. Testers, but not participants, were blinded to treatment allocation. Analysis was on an intent-to-treat basis. We reassessed 88.5% of the children in the original study (n = 1,256). Factor analysis of test scores yielded 2 factors: cognitive (cognition, language, school readiness, executive function) and behavioural. We found no effect of the interventions after 2 years on the cognitive factor (PS: -0.031 SD, 95% CI -0.229-0.167; MN: -0.042 SD, 95% CI -0.249-0.164; PS and MN: -0.111 SD, 95% CI -0.311-0.089), the behavioural factor (PS: 0.013 SD, 95% CI -0.172-0.198; MN: 0.071 SD, 95% CI -0.115-0.258; PS and MN: 0.062 SD, 95% CI -0.115-0.239), or home stimulation. Study limitations include that behavioural development was measured through maternal report and that very small effects may have been missed, despite the large sample size.Conclusions: We found no evidence that a scalable PS intervention benefited children's development 2 years after it ended. It is possible that the initial effects on child development were too small to be sustained or that the lack of continued impact on home stimulation contributed to fade out. Both are likely related to compromises in implementation when going to scale and suggest one should not extrapolate from medium-term effects of small efficacy trials to scalable interventions. Understanding the salient differences between small efficacy trials and scaled-up versions will be key to making ECD interventions effective tools for policymakers.Trial Registration: ISRCTN18991160. [ABSTRACT FROM AUTHOR]