Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

BACKGROUND: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. SETTING: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. METHODS: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. RESULTS: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. CONCLUSION: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.

Undernutrition in children aged 0-59 months by region and over time: secondary analysis of the Burkina Faso 2012-2018 National Nutrition Surveys.

The global burden of undernutrition remains high, responsible for significant under-five mortality in resource-limited settings. Numerous sustainable development goals (SDGs) are linked to nutrition, and nationally representative nutrition surveillance is a key activity to track progress towards SDGs and guide efficient programmes. OBJECTIVES: The aim of this study is to look at spatial and temporal trends in undernutrition in children under 5 years age in Burkina Faso. SETTING: We used data from annual National Nutrition Surveys using Standardised Monitoring and Assessment of Relief and Transitions methodology (anthropometry, morbidity) over 7 years (2012-2018) in Burkina Faso. PARTICIPANTS: Children of under 5 years from households selected through systemic sampling at countrywide level. MAIN OUTCOME MEASURES: Prevalence of stunting (height-for-age z-score, <-2), underweight (weight-for-age z-score, <-2) and wasting (weight-for-height z-score, <-2) at regional and national. We used general linear mixed models, adjusted by age, survey year, sex, presence of fever and/or diarrhoea, and poverty index to quantify the risk of undernutrition over time and by region of residence. RESULTS: Between 2012 and 2018, decreases were observed overall in the prevalence of growth retardation (stunting) decreased from 33.0% (95% CI 32.3 to 33.8) in 2012 to 26.7% (95% CI 26.2 to 27.3) in 2018. Underweight reduced from 24.4% (95% CI 23.7 to 25.1) to 18.7% (95% CI 18.2 to 19.2) for the same period and wasting decreased from 10.8% (95% CI 10.3 to 11.3) in 2012 to 8.4% (95% CI 8.1 to 8.8) in 2018. However, there was substantial variation across the country, with increased risk of undernutrition in the regions of Sahel, East and Cascades primarily. High-risk regions were characterised by a lower poverty index and limited access to healthcare services. CONCLUSIONS: Our findings could inform national policymakers in refining and optimising resource allocation based on the identification of high-risk areas.

Pregnancy and neonatal safety outcomes of timing of initiation of daily oral tenofovir disoproxil fumarate and emtricitabine pre-exposure prophylaxis for HIV prevention (CAP016): an open-label, randomised, non-inferiority trial.

BACKGROUND: The safety of tenofovir disoproxil fumarate and emtricitabine as pre-exposure prophylaxis (PrEP) in pregnant women not living with HIV is uncertain. We aimed to compare pregnancy and neonatal outcomes in women exposed and not exposed to PrEP during pregnancy. METHODS: In this single-site, open-label, randomised, non-inferiority trial in Durban, South Africa, we evaluated pregnancy and neonatal outcomes in pregnant women aged 18 years or older, not living with HIV, and at 14-28 weeks' gestation at the time of enrolment. Eligible participants were randomly assigned (1:1) using a computer-generated permuted block (block size of ten) randomisation list to immediate initiation or deferred initiation of PrEP until breastfeeding cessation. Participants in the immediate PrEP group received a monthly supply of once daily oral tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg. Participants in the deferred PrEP group received standard of care for HIV prevention. The primary outcomes were the occurrence of preterm live birth (<37 weeks gestational age) and very preterm birth (<34 weeks gestational age) determined by menstrual dating, low birthweight (<2500 g), very low birthweight (<1500 g), stillbirth (≥20 weeks gestational age), and small for gestational age (birthweight less than the tenth percentile). Post-natal safety outcomes will be reported elsewhere. We used binomial regression models to estimate risk differences and two-sided 90% CIs. Immediate PrEP was non-inferior to deferred PrEP if the upper bound of the 90% CI of the risk difference was less than the upper predefined non-inferiority margin for preterm birth (7·5%), very preterm birth (2·6%), low birthweight (5·5%), very low birthweight (1·2%), stillbirth (1·0%), and small for gestational age (3·7%). All outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT3227731. FINDINGS: Between Sept 25, 2017, and Dec 6, 2019, we screened 693 women, of whom 540 were randomly assigned to immediate PrEP (n=271) or deferred PrEP (n=269). The median gestational age was 19 weeks (IQR 15-23 for immediate PrEP and 16-23 for deferred PrEP). The risk difference between the immediate PrEP group and the deferred PrEP group for preterm birth was -4·7% (90% CI -10·7 to 1·2; immediate PrEP was non-inferior), for very preterm birth was 0·6% (-3·4 to 4·6; upper limit exceeded the non-inferiority margin), for low birthweight was 2·5% (-1·6 to 6·6; upper limit exceeded the non-inferiority margin), for very low birthweight was 0% (-1·4 to 1·4; upper limit exceeded the non-inferiority margin), for stillbirth was 1·2% (-1·5 to 3·8; upper limit exceeded the non-inferiority margin), and for small for gestational age was 0·9% (-1·2 to 2·9; immediate PrEP was non-inferior). INTERPRETATION: In our study, PrEP was not associated with preterm birth or small for gestational age infants. Our data support the use of tenofovir disoproxil fumarate and emtricitabine in pregnancy and our reassuring findings can be used to allay safety concerns among pregnant women. FUNDING: South African Medical Research Council and Gilead Sciences.

Maternal socioeconomic status and infant feeding practices underlying pathways to child stunting in Cambodia: structural path analysis using cross-sectional population data.

OBJECTIVES: To identify and investigate complex pathways to stunting among children aged 6-24 months to determine the mediating effects of dietary diversity and continued breast feeding on the association between socioeconomic factors and child stunting. DESIGN, SETTING AND PARTICIPANTS: We analysed the most recent cross-sectional Demographic and Health Survey data from Cambodia (2014). We applied structural path analysis on a sample of 1365 children to model the complex and inter-related pathways of factors determining children's height for age. Explanatory variables included a composite indicator of maternal employment, household wealth, maternal education, current breastfeeding status and dietary diversity score. Results are presented both in terms of non-standardised and standardised coefficients. OUTCOME MEASURE: The primary outcome measure was height-for-age Z-scores as a continuous measure. RESULTS: Findings suggest that children's dietary diversity and continued breast feeding mediate the association between socioeconomic status and children's height. While there was no significant direct effect of maternal education on children's height, results suggested significant indirect pathways through which maternal education effects children's height; operating through household wealth, maternal employment, dietary diversity and continued breastfeeding status (p<0.001). Most notably, 41% of the effect of maternal employment on children's height was mediated by either dietary diversity or continued breast feeding. CONCLUSION: We provide evidence to support targeted nutrition interventions which account for the different ways in which underlying socioeconomic factors influence infant and young child feeding practices, and the potential impact on child nutritional status.

Children born during the hunger season are at a higher risk of severe acute malnutrition: Findings from a Guinea Sahelian ecological zone in Northern Ghana.

Heightened food insecurity in the hunger season increases the risk of severe acute malnutrition (SAM) in childhood. This study examined the association of season of birth with SAM in a Guinean Sahelian ecological zone. We analyzed routine health and sociodemographic surveillance data from the Navrongo Health and Socio-demographic Surveillance System collected between 2011 and 2018. January-June, the period of highest food insecurity, was defined as the hunger season. We defined moderate acute malnutrition as child mid-upper arm circumference (MUAC) between 115 mm and 135 mm and SAM as MAUC ≤ 115 mm. We used adjusted logistic regression to quantify the association between the season of birth and SAM in children aged 6-35 months. From the 29,452 children studied, 24% had moderate acute malnutrition. Overall, 1.4% had SAM, with a higher prevalence (1.8%) in the hunger season of birth. Compared with those born October-December, adjusted odds ratios (aOR) and 95% confidence interval (95% CI) for SAM were increased for children born in the hunger season: January-March (1.77 [1.31-2.39]) and April-June (1.92 [1.44-2.56]). Low birth weight, age at an assessment of nutritional status, and ethno-linguistic group were also significantly associated with SAM in adjusted analyses. Our study established that being born in the hunger season is associated with a higher risk of severe acute malnutrition. The result implies improvement in the food supply to pregnant and lactating mothers through sustainable agriculture or food system change targeting the hunger season may reduce the burden of severe acute malnutrition.

Pregnancy outcomes in women living with HIV and HIV-negative women in South Africa: Cohort analysis based on bias-corrected gestational age.

BACKGROUND: Antiretroviral therapy (ART) use during pregnancy may be associated with adverse outcomes, but findings have been inconsistent, at least in part due to unreliably estimated gestational age. OBJECTIVE: To quantify the association between HIV status, ART initiation timing and adverse birth outcomes, with reliably assessed gestational age at booking, in a public sector primary care facility in Cape Town, South Africa. METHODS: Pregnant women, HIV-negative or living with HIV (WLHIV), were enrolled at first antenatal care visit and followed through delivery. Ultrasound-assessed gestational age was deemed the gold standard. Based on quantitative bias analysis for outcome misclassification, gestational age by non-ultrasound assessment was corrected using multiple overimputation, which deals with missing data and measurement error simultaneously. Using bias-corrected gestational age, birth outcomes were compared between WLHIV and HIV-negative women, and among WLHIV who initiated ART before versus during pregnancy, further divided into trimesters. RESULTS: Of 3952 women enrolled, 37% were WLHIV (mostly using tenofovir + emtricitabine + efavirenz). Last menstrual period (LMP)-based gestational age was identified to be biased, and LMP measures were thus corrected using multiple overimputation. Comparing WLHIV and HIV-negative women, adjusted risk ratio (aRR) of overall pregnancy loss was 1.26 (95% confidence interval [CI] 0.98, 1.61); aRR of preterm delivery was 1.02 (95% CI 0.88, 1.20); aRR of small for gestational age infants was 1.43 (95% CI 1.14, 1.80). Among WLHIV, outcomes were similar by ART initiation timing. CONCLUSIONS: In this routine care cohort, risk of SGA, and possibly of pregnancy loss, was increased in WLHIV compared with HIV-negative women, with no evidence of increased risk of preterm delivery. Further research is needed to improve mechanistic understanding of the contribution of ART to adverse birth outcomes to optimize treatment for pregnant WLHIV and ensure optimal maternal and infant outcomes.

Cohort profile: Prematurity Immunology in Mothers living with HIV and their infants Study (PIMS).

PURPOSE: Prematurity Immunology in Mothers living with HIV and their infants Study (PIMS) is a prospective cohort study in South Africa investigating the association between antiretroviral therapy (ART) use, preterm delivery (PTD) and small-for-gestational age (SGA) live births. PIMS main hypotheses are that ART initiation in pregnancy and ART-induced hypertension are associated with PTD and SGA respectively and that reconstitution of cellular immune responses in women on ART from before pregnancy results in increases in PTD of GA infants. PARTICIPANTS: Pregnant women (n=3972) aged ≥18 years regardless of HIV status recruited from 2015 to 2016 into the overall PIMS cohort (2517 HIV-negative, 1455 living with HIV). A nested cohort contained 551 women living with HIV who were ≤24 weeks' GA on ultrasound: 261 initiated ART before pregnancy, 290 initiated during the pregnancy. FINDINGS TO DATE: Women in the overall cohort were followed antenatally through to delivery using routine clinical records; further women in the nested cohort were actively followed up until 12 months post partum, with data collected on maternal health (HIV care and ART use, clinical care and intercurrent clinical history). Other procedures conducted on the nested cohort included physical examinations (anthropometry, blood pressure measurement), assessment of fetal growth (ultrasound), maternal and infant phlebotomy for storage of plasma, RNA and peripheral blood mononuclear cells, collection of delivery specimens (placenta and cord blood) and infant 12-month developmental assessment. Preliminary findings have contributed to our understanding of risk factors for adverse birth outcomes, and the relationship between pregnancy immunology, HIV/ART and adverse birth outcomes. FUTURE PLANS: Using specimens collected from study participants living with HIV throughout pregnancy and first year of life, the PIMS provides a valuable platform for answering a variety of research questions focused on temporal changes of immunology markers in women whose immune status is altered by HIV infection, and how ART initiated during the pregnancy affects immune responses. The relationship between these immunological changes with adverse birth outcomes as well as possible longer-term impact of exposure to ART in fetal and early life will be explored. Additionally, further active and passive follow-up of mothers and their infants is planned at school-going age and beyond to chart growth, morbidity and development, as well as changes in family circumstances.

Stakeholder Perspectives on Barriers and Facilitators on the Implementation of the 1000 Days Plus Nutrition Policy Activities in Ghana.

Optimizing nutrition in the preconception and 1000 days periods have long-term benefits such as higher economic productivity, reduced risk of related non-communicable diseases and increased health and well-being. Despite Ghana's recent progress in reducing malnutrition, the situation is far from optimal. This qualitative study analyzed the maternal and child health nutrition policy framework in Ghana to identify the current barriers and facilitators to the implementation of nutrition policies and programs relating to the first 1000 days plus. Data analyzed included in-depth interviews and focus group discussions conducted in Ghana between March and April 2019. Participants were composed of experts from government agencies, civil society organizations, community-based organizations and international partners at national and subnational levels. Seven critical areas were identified: planning policy implementation, resources, leadership and stakeholders' engagement, implementation guidance and ongoing communication, organizational culture, accountability and governance and coverage. The study showed that, to eradicate malnutrition in Ghana, priorities of individual stakeholders have to be merged and aligned into a single 1000 days plus nutrition policy framework. Furthermore, this study may support stakeholders in implementing successfully the 1000 days plus nutrition policy activities in Ghana.

Differential impact of antiretroviral therapy initiated before or during pregnancy on placenta pathology in HIV-positive women.

OBJECTIVE: To examine the association between timing of antiretroviral treatment (ART) initiation in HIV-infected women and placental histopathology. DESIGN: A nested substudy in a larger cohort of HIV-infected women which examined the association between ART status and birth outcomes. METHODS: Placentas (n = 130) were examined for histopathology from two ART groups: stable (n = 53), who initiated ART before conception and initiating (n = 77), who started ART during pregnancy [median (interquartile range) 15 weeks gestation (11-18)]. Using binomial regression we quantified associations between ART initiation timing with placental histopathology and pregnancy outcomes. RESULTS: One-third of all placentas were less than 10th percentile weight-for-gestation and there was no significant difference between ART groups. Placental diameter, thickness, cord insertion position and foetal-placental weight ratio were also similar by group. However, placentas from the stable group showed increased maternal vascular malperfusion (MVM) (39.6 vs. 19.4%), and decreased weight (392 vs. 422 g, P = 0.09). MVM risk was twice as high [risk ratios 2.03 (95% confidence interval: 1.16-3.57); P = 0.01] in the stable group; the increased risk remaining significant when adjusting for maternal age [risk ratios 2.04 (95% confidence interval: 1.12-3.72); P = 0.02]. Furthermore, MVM was significantly associated with preterm delivery and low birth weight (P = 0.002 and <0.0001, respectively). CONCLUSION: Preconception initiation of ART was associated with an increased MVM risk, and may contribute to placental dysfunction. The association between MVM with preterm delivery and low birth weight suggests that a placenta-mediated mechanism likely links the putative association between long-term use of ART and adverse birth outcomes.

Low Immune Activation in Early Pregnancy Is Associated With Preterm But Not Small-for-gestational-age Delivery in Women Infected With Human Immunodeficiency Virus Initiating Antiretroviral Therapy in Pregnancy: A Prematurity Immunology in HIV-infected Mothers and their Infants Study (PIMS) Case-control Study in Cape Town, South Africa.

BACKGROUND: Mechanisms underlying an association between human immunodeficiency virus (HIV) or antiretroviral therapy (ART) during pregnancy with risk of preterm delivery (PTD) and small-for-gestational-age (SGA) remain unclear. We explored the association between cellular immune activation and PTD or SGA in women with HIV initiating ART during or before pregnancy. METHODS: Women with HIV enrolled at median 15 weeks' gestation, were analyzed for immune markers, and matched on ART initiation timing (15 women initiated pre- and 15 during pregnancy). There were 30 PTD (delivery <37 weeks), 30 SGA (weight for age ≤10th percentile) cases, and 30 controls (term, weight for gestational age >25th percentile) as outcomes. Lymphocytes, monocytes, and dendritic cell populations and their activation status or functionality were enumerated by flow cytometry. RESULTS: PTD cases initiating ART in pregnancy showed decreased CD8+ T cell, monocyte, and dendritic cell activation; increased classical (CD14+CD16-) and intermediate (CD14+CD16+) monocyte frequencies; and decreased inflammatory monocytes (CD14dimCD16+) compared with SGA cases and term controls (all P < .05). Allowing for baseline viral load, the immune markers remained significantly associated with PTD but only in women initiating ART in pregnancy. Lower monocyte activation was predictive of PTD. TLR ligand-induced interferon-α and macrophage inflammatory protein-1ß levels in monocytes were significantly lower in PTD women initiating ART in pregnancy. CONCLUSION: Low immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation were associated with PTD but not SGA among women initiating ART in, but not before, pregnancy, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women initiating ART in pregnancy.

Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings: a cost-effectiveness analysis.

INTRODUCTION: Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation. METHODS: Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Côte d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS). RESULTS: With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. CONCLUSIONS: Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.

Methodological Considerations for Preterm Birth Research.

Complications from preterm birth are a leading cause of infant mortality, with long-term implications for morbidity and quality of life of preterm infants. There are many important risk factors for preterm births however in this article, we focus on the maternal infection etiological pathway, given its significance in low-to-middle income countries. In high preterm birth settings such as sub-Saharan Africa, maternal HIV infection and antiretroviral therapy (ART) use have been associated with an increased risk of preterm births. Consequently, we highlight methodological considerations related to selection and measurement bias in preterm birth research. We further illustrate the potential impact of these biases in studies investigating the relationship between HIV/ART and preterm births. We also briefly discuss issues related to population-level estimations based on routinely collected clinical or civil registration data. We conclude by emphasizing the importance of strengthening of antenatal care services to improve quality of population data as well as optimizing current and future study designs, by taking into account the important methodological considerations described in this article.

Realising the potential human development returns to investing in early and maternal nutrition: The importance of identifying and addressing constraints over the life course.

The benefits of interventions which improve early nutrition are well recognised. These benefits, however, only accrue to the extent that later life circumstances allow. Consequently, in adverse contexts many of the benefits will never be realised, particularly for the most vulnerable, exacerbating inequality. Returns to investment in early nutrition could be improved if we identified contextual factors constraining their realisation and interventions to weaken these. We estimate cost and impact of scaling 10 nutrition interventions for a cohort of South African children born in 2021. We estimate associated declines in malnutrition and mortality, and improvements in years of schooling and future earnings. To examine the role of context over the life-course we estimate benefits with and without additional improvements in school quality and employment opportunities by socio-economic quintile. Scale up reduces national stunting (height for age < = -2SD) rates among children at 24 months by 3.18 percentage points, implying an increase in mean height for age z-score (HAZ) of 0.10, and 53,000 years of additional schooling. Quintile 1 (the poorest) displays the largest decline in stunting, and largest increase in mean HAZ. Estimated total cost of increasing coverage of the interventions for the cohort is US$90 million. The present value of the additional years of schooling is estimated at close to US$2 billion. Cost-benefit ratios suggest the highest return occurs in quintile 5 (1:23). Reducing inequality in school quality closes the gap between quintile 5 and the lower quintiles. If school quality and labour force participation were equal the highest returns are in quintile 1(1:31). An enabling environment is key to maximising human development returns from investing in early nutrition, and to avoid exacerbating existing inequality. Therefore, particularly for children in adverse conditions, it is essential to identify and implement complementary interventions over the life course.

Understanding how maternal social and biological factors are related to fetal growth in an urban South African cohort.

The aim of this study was to identify social and biological drivers of fetal growth by examining associations with household, preconception, and pregnancy factors in a cohort from Soweto, South Africa. Complete data and ultrasound scans were collected on 519 women between 2013 and 2016 at 6 time points during pregnancy (<14, 14-18, 19-23, 24-28, 29-33 weeks, and 34-38 weeks). Household-level factors, preconception health, baseline body mass index (BMI), and demographic data were collected at the first visit. During pregnancy, gestational weight gain (GWG; kg/week) was calculated. At 24-28 weeks of gestation, oral glucose tolerance test was used to determine gestational diabetes mellitus (GDM) status, and hypertension status was characterised. Longitudinal growth in head circumference, abdominal circumference, biparietal diameter, and femur length were modelled using the Superimposition by Translation and Rotation, a shape-invariant model which produces growth curves against gestational age. A priori identified exposure variables were then included in a series of sex-stratified hierarchical regression models for each fetal growth outcome. No household-level factors were associated with fetal growth. Maternal BMI at baseline was positively associated with all outcome parameters in males and females. Both GWG (in males and females) and GDM (in males) were significant positive predictors of abdominal growth. Males showed more responsiveness to abdominal growth, while females were more responsive to linear growth. Thus, fetal growth was largely predicted by maternal biological factors, and sexual dimorphism in the responsiveness of fetal biometry to biological exposures was evident.

Supporting maternal and child nutrition: views from community members in rural Northern Ghana.

OBJECTIVE: Despite efforts to improve maternal and child nutrition, undernutrition remains a major public health challenge in Ghana. The current study explored community perceptions of undernutrition and context-specific interventions that could improve maternal and child nutrition in rural Northern Ghana. DESIGN: This exploratory qualitative study used ten focus group discussions to gather primary data. The discussions were recorded, transcribed and coded into themes using Nvivo 12 software to aid thematic analysis. SETTING: The study was conducted in rural Kassena-Nankana Districts of Northern Ghana. STUDY PARTICIPANTS: Thirty-three men and fifty-one women aged 18-50 years were randomly selected from the community. RESULTS: Most participants reported poverty, lack of irrigated agricultural land and poor harvests as the main barriers to optimal nutrition. To improve maternal and child nutrition, study participants suggested that the construction of dams at the community level would facilitate all year round farming including rearing of animals. Participants perceived that the provision of agricultural materials such as high yield seedlings, pesticides and fertiliser would help boost agricultural productivity. They also recommended community-based nutrition education by trained health volunteers, focused on types of locally produced foods and appropriate ways to prepare them to help improve maternal and child nutrition. CONCLUSION: Drawing on these findings and existing literature, we argue that supporting community initiated nutrition interventions such as improved irrigation for dry season farming, provision of agricultural inputs and community education could improve maternal and child nutrition.

Community perspectives on maternal and child health during nutrition and economic transition in sub-Saharan Africa.

OBJECTIVE: To explore community perceptions on maternal and child nutrition issues in Sub-Saharan Africa. DESIGN: Thirty focus groups with men and women from three communities facilitated by local researchers. SETTING: One urban (Soweto, South Africa) and two rural settings (Navrongo, Ghana and Nanoro, Burkina Faso) at different stages of economic transition. PARTICIPANTS: Two hundred thirty-seven men and women aged 18-55 years, mostly subsistence farmers in Navrongo and Nanoro and low income in Soweto. RESULTS: Differences in community concerns about maternal and child health and nutrition reflected the transitional stage of the country. Community priorities revolved around poor nutrition and hunger caused by poverty, lack of economic opportunity and traditional gender roles. Men and women felt they had limited control over food and other resources. Women wanted men to take more responsibility for domestic chores, including food provision, while men wanted more involvement in their families but felt unable to provide for them. Solutions suggested focusing on ways of increasing control over economic production, family life and domestic food supplies. Rural communities sought agricultural support, while the urban community wanted regulation of the food environment. CONCLUSIONS: To be acceptable and effective, interventions to improve maternal and child nutrition need to take account of communities' perceptions of their needs and address wider determinants of nutritional status and differences in access to food reflecting the stage of the country's economic transition. Findings suggest that education and knowledge are necessary but not sufficient to support improvements in women's and children's nutritional status.

'Men are not playing their roles', maternal and child nutrition in Nanoro, Burkina Faso.

OBJECTIVE: To collect context-specific insights into maternal and child health and nutrition issues, and to explore potential solutions in Nanoro, Burkina Faso. DESIGN: Eleven focus groups with men and women from eleven communities, facilitated by local researchers. SETTING: The study took place in the Nanoro Health district, in the West-Central part of Burkina Faso. PARTICIPANTS: Eighty-six men (18-55 years) and women by age group: 18-25; 26-34 and 35-55 years, participated in the group discussions. RESULTS: Participants described barriers to optimal nutrition of mothers and children related to a range of community factors, with gender inequality as central. Major themes in the discussions are related to poverty and challenges generated by socially and culturally determined gender roles. Sub-themes are women lacking access to food whilst pregnant and having limited access to health care and opportunities to generate income. Although communities believe that food donations should be implemented to overcome this, they also pointed out the need for enhancing their own food production, requiring improved agricultural technologies. Given the important role that women could play in reducing malnutrition, these communities felt they needed to be empowered to do so and supported by men. They also felt that this had to be carried out in the context of an enhanced health care system. CONCLUSIONS: Findings reported here highlight the importance of nutrition-sensitive interventions and women's empowerment in improving maternal and child nutrition. There is a need to integrate a sustainable multi-sectorial approach which goes beyond food support.

Blood pressure trajectories during pregnancy and associations with adverse birth outcomes among HIV-infected and HIV-uninfected women in South Africa: a group-based trajectory modelling approach.

BACKGROUND: High blood pressure (BP) late in pregnancy is associated with preterm delivery (PTD); BP has also been associated with HIV and antiretroviral therapy (ART), but whether the relationship between BP assessed longitudinally over pregnancy and PTD and low birthweight (LBW) is modified by HIV/ART is unclear. We hypothesise the presence of distinctive BP trajectories and their association with adverse birth outcomes may be mediated by HIV/ART status. METHODS: We recruited pregnant women at a large primary care facility in Cape Town. BP was measured throughout pregnancy using automated monitors. Group-based trajectory modelling in women with ≥3 BP measurements identified distinct joint systolic and diastolic BP trajectory groups. Multinomial regression assessed BP trajectory group associations with HIV/ART status, and Poisson regression with robust error variance was used to assess risk of PTD and LBW. RESULTS: Of the 1583 women in this analysis, 37% were HIV-infected. Seven joint trajectory group combinations were identified, which were categorised as normal (50%), low normal (25%), high normal (20%), and abnormal (5%). A higher proportion of women in the low normal group were HIV-infected than HIV-uninfected (28% vs. 23%), however differences were not statistically significant (RR 1.27, 95% CI 0.98-1.63, reference category: normal). In multivariable analyses, low normal trajectory (aRR0.59, 0.41-0.85) was associated with decreased risk of PTD, while high normal (aRR1.48, 1.12-1.95) and abnormal trajectories (aRR3.18, 2.32-4.37) were associated with increased risk of PTD, and abnormal with increased risk of LBW (RR2.81, 1.90-4.15). CONCLUSIONS: While HIV/ART did not appear to mediate the BP trajectories and adverse birth outcomes association, they did provide more detailed insights into the relationship between BP, PTD and LBW for HIV-infected and uninfected women.

Neurodevelopment of HIV-exposed uninfected children in Cape Town, South Africa.

BACKGROUND: Evidence shows that antiretroviral (ART) exposure is associated with neurodevelopmental delays in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children. However, there are few insights into modifiable maternal and child factors that may play a role in improving neurodevelopment in HEU children. We used a parent-centric neurodevelopment tool, Ages & Stages Questionnaire (ASQ) to examined neurodevelopment in HEU children at 12-24 months of age, and associations with maternal and child factors. METHODS: 505 HIV-infected women (initiated ART pre- or during pregnancy) with live singleton births attending primary health care were enrolled; 355 of their HEU children were assessed for neurodevelopment (gross motor, fine motor, communication, problem solving and personal-social domains) at 12-24 months using age-specific ASQ administered by a trained fieldworker. Associations with maternal and child factors were examined using logistic regression models. RESULTS: Among mothers (median age 30 years, IQR, 26-34), 52% initiated ART during pregnancy; the median CD4 count was 436 cells/µl (IQR, 305-604). Most delayed neurodevelopment in HEU children was in gross (9%) and fine motor (5%) functions. In adjusted models, maternal socio-economic status (aOR 0.42, 95% CI 0.24-0.76) was associated with reduced odds of delayed gross-fine motor neurodevelopment. Maternal age ≥35 years (aOR 0.22, 95% CI 0.05-0.89) and maternal body mass index (BMI) <18.5 (aOR 6.76, 95% CI 1.06-43.13) were associated with delayed communication-problem-solving-personal-social neurodevelopment. There were no differences in odds for either domain by maternal ART initiation timing. CONCLUSIONS: Delayed neurodevelopment was detected in both gross and fine motor functions in this cohort of HEU children, with strong maternal predictors that may be explored as potentially modifiable factors associated with neurodevelopment at one to two years of age.

The allocation of USdollar;105 billion in global funding from G20 countries for infectious disease research between 2000 and 2017: a content analysis of investments.

BACKGROUND: Each year, billions of US$ are spent globally on infectious disease research and development. However, there is little systematic tracking of global research and development. We present research on investments into infectious diseases research from funders in the G20 countries across an 18-year time period spanning 2000-17, comparing amounts invested for different conditions and considering the global burden of disease to identify potential areas of relative underfunding. METHODS: The study examined research awards made between 2000 and 2017 for infectious disease research from G20-based public and philanthropic funders. We searched research databases using a range of keywords, and open access data were extracted from funder websites. Awards were categorised by type of science, specialty, and disease or pathogen. Data collected included study title, abstract, award amount, funder, and year. We used descriptive statistics and Spearman's correlation coefficient to investigate the association between research investment and disease burden, using Global Burden of Disease 2017 study data. FINDINGS: The final 2000-17 dataset included 94 074 awards for infectious disease research, with a sum investment of $104·9 billion (annual range 4·1 billion to 8·4 billion) and a median award size of $257 176 (IQR 62 562-770 661). Pre-clinical research received $61·1 billion (58·2%) across 70 337 (74·8%) awards and public health research received $29·5 billion (28·1%) from 19 197 (20·4%) awards. HIV/AIDS received $42·1 billion (40·1%), tuberculosis received $7·0 billion (6·7%), malaria received $5·6 billion (5·3%), and pneumonia received $3·5 billion (3·3%). Funding for Ebola virus ($1·2 billion), Zika virus ($0·3 billion), influenza ($4·4 billion), and coronavirus ($0·5 billion) was typically highest soon after a high-profile outbreak. There was a general increase in year-on-year investment in infectious disease research between 2000 and 2006, with a decline between 2007 and 2017. Funders based in the USA provided $81·6 billion (77·8%). Based on funding per 2017 disability-adjusted life years (DALYs), HIV/AIDS received the greatest relative investment ($772 per DALY), compared with tuberculosis ($156 per DALY), malaria ($125 per DALY), and pneumonia ($33 per DALY). Syphilis and scabies received the least relative investment (both $9 per DALY). We observed weak positive correlation (r=0·30) between investment and 2017 disease burden. INTERPRETATION: HIV research received the highest amount of investment relative to DALY burden. Scabies and syphilis received the lowest relative funding. Investments for high-threat pathogens (eg, Ebola virus and coronavirus) were often reactive and followed outbreaks. We found little evidence that funding is proactively guided by global burden or pandemic risk. Our findings show how research investments are allocated and how this relates to disease burden and diseases with pandemic potential. FUNDING: Bill & Melinda Gates Foundation.