SummaryBackgroundFast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults.MethodsWe used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth (relative weight gain) in three age periods: 0–2 years, 2 years to mid-childhood, and mid-childhood to adulthood.FindingsWe obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m2 (odds ratio 1·28, 95% CI 1·21–1·35) and a reduced likelihood of short adult stature (0·49, 0·44–0·54) and of not completing secondary school (0·82, 0·78–0·87). Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20–0·52; mid-childhood: 0·39, 0·36–0·43) and of not completing secondary school (age 2 years: 0·74, 0·67–0·78; mid-childhood: 0·87, 0·83–0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17–1·31; mid-childhood: 1·12, 1·06–1·18) and elevated blood pressure (age 2 years: 1·12, 1·06–1·19; mid-childhood: 1·07, 1·01–1·13). Faster relative weight gain was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43–1·60; mid-childhood: 1·76, 1·69–1·91) and elevated blood pressure (age 2 years: 1·07, 1·01–1·13; mid-childhood: 1·22, 1·15–1·30). Linear growth and relative weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the disorder (0·89, 0·81–0·98).InterpretationInterventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs.FundingWellcome Trust and Bill & Melinda Gates Foundation.

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterisation of African genetic diversity is needed. The African Genome Variation Project (AGVP) provides a resource to help design, implement and interpret genomic studies in sub-Saharan Africa (SSA) and worldwide. The AGVP represents dense genotypes from 1,481 and whole genome sequences (WGS) from 320 individuals across SSA. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across SSA. We identify new loci under selection, including for malaria and hypertension. We show that modern imputation panels can identify association signals at highly differentiated loci across populations in SSA. Using WGS, we show further improvement in imputation accuracy supporting efforts for large-scale sequencing of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa, showing for the first time that such designs are feasible.

BACKGROUNDTwo drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeiciency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low-and middle-income countries. METHODSWe conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs -TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) -against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, −10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTSA total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONSTreatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.

Background Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low- and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. Methods Pooled data from five birth cohorts (total N=19,403) in Brazil, Guatemala, India, the Philippines and South Africa were used to examine associations of maternal age with offspring birth weight, gestational age, height-for-age and weight-for-height Z-scores in childhood, attained schooling, and adult height, body composition (BMI, waist circumference, fat and lean mass) and cardiometabolic risk factors (blood pressure and fasting plasma glucose concentration), along with binary variables derived from these. Analyses were unadjusted and adjusted for maternal socio-economic status, height and parity, and breastfeeding duration. Findings In unadjusted analyses, younger (≤19 years) and older (≥35 years) maternal age was associated with lower birth weight, gestational age, child nutritional status and schooling. Associations with younger maternal age remained after adjustment; odds ratios (OR) for low birth weight, pre-term birth, 2-year stunting and failure to complete secondary schooling were 1·18 (95% CI: 1·02,1·36), 1·26 (1·03,1·53), 1·46 (1·25,1·70) and 1·38 (1·18,1·62) respectively compared with mothers aged 20-24 years. After adjustment, older maternal age remained associated with increased risk of pre-term birth (OR=1·33 (1·05,1·67)) but children of older mothers had less 2-year stunting (OR=0·64 (0·54,0·77)) and failure to complete secondary schooling (OR=0·59 (0·48,0·71)). Offspring of both younger and older mothers had higher adult fasting glucose concentrations (~0·05 mmol/l). Interpretation Children of young mothers in LMICs are disadvantaged at birth and in childhood nutrition and schooling. Efforts to prevent early childbearing should be strengthened. After adjusting for confounders, children of older mothers have advantages in nutritional status and schooling. Extremes of maternal age may be associated with disturbed offspring glucose metabolism. Funding Wellcome Trust, Bill and Melinda Gates Foundation

The co-occurrence of health burdens in transitioning populations, particularly in specific socioeconomic and cultural contexts, calls for conceptual frameworks to improve understanding of risk factors, so as to better design and implement prevention and intervention programmes to address comorbidities. The concept of a syndemic, developed by medical anthropologists, provides such a framework for preventing and treating comorbidities. The term syndemic refers to synergistic health problems that affect the health of a population within the context of persistent social and economic inequalities. Until now, syndemic theory has been applied to comorbid health problems in poor immigrant communities in high-income countries with limited translation, and in low-income or middle-income countries. In this Series paper, we examine the application of syndemic theory to comorbidities and multimorbidities in low-income and middle-income countries. We employ diabetes as an exemplar and discuss its comorbidity with HIV in Kenya, tuberculosis in India, and depression in South Africa. Using a model of syndemics that addresses transactional pathophysiology, socioeconomic conditions, health system structures, and cultural context, we illustrate the different syndemics across these countries and the potential benefit of syndemic care to patients. We conclude with recommendations for research and systems of care to address syndemics in low-income and middle-income country settings.

The nutritional status of both women and men before conception has profound implications for the growth, development, and long-term health of their offspring. Evidence of the effectiveness of preconception interventions for improving outcomes for mothers and babies is scarce. However, given the large potential health return, and relatively low costs and risk of harm, research into potential interventions is warranted. We identified three promising strategies for intervention that are likely to be scalable and have positive effects on a range of health outcomes: supplementation and fortification; cash transfers and incentives; and behaviour change interventions. On the basis of these strategies, we suggest a model specifying pathways to effect. Pathways are incorporated into a life-course framework using individual motivation and receptiveness at different preconception action phases, to guide design and targeting of preconception interventions. Interventions for individuals not planning immediate pregnancy take advantage of settings and implementation platforms outside the maternal and child health arena, since this group is unlikely to be engaged with maternal health services. Interventions to improve women's nutritional status and health behaviours at all preconception action phases should consider social and environmental determinants, to avoid exacerbating health and gender inequalities, and be underpinned by a social movement that touches the whole population. We propose a dual strategy that targets specific groups actively planning a pregnancy, while improving the health of the population more broadly. Modern marketing techniques could be used to promote a social movement based on an emotional and symbolic connection between improved preconception maternal health and nutrition, and offspring health. We suggest that speedy and scalable benefits to public health might be achieved through strategic engagement with the private sector. Political theory supports the development of an advocacy coalition of groups interested in preconception health, to harness the political will and leadership necessary to turn high-level policy into effective coordinated action.

No abstract

H3Africa is developing capacity for health-related genomics research in Africa