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.

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.

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.

'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.

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.

Elevated body mass index during pregnancy and gestational weight gain in HIV-infected and HIV-uninfected women in Cape Town, South Africa: association with adverse birth outcomes.

OBJECTIVES: To examine the association between maternal body mass index (BMI) and gestational weight gain (GWG) and adverse birth outcomes in HIV-infected and HIV-uninfected women. METHODS: In an urban South African community, 2921 consecutive HIV-infected and HIV-uninfected pregnant women attending primary healthcare services were assessed at their first antenatal visit. A subset of HIV-infected women enrolled in a longitudinal study was assessed three times during pregnancy. All women had birth outcome data from medical records and study questionnaires. In analyses, the associations between BMI, GWG, maternal factors and adverse birth outcomes were assessed with logistic regression models. RESULTS: The estimated pre-pregnancy BMI median was 29 kg/m2 (IQR, 24-34) overall, 29 kg/m2 (IQR, 24-34) for HIV-uninfected and 28 kg/m2 (IQR, 24-34) for HIV-infected women; HIV prevalence was 38%. In adjusted models, increased BMI in the overall cohort was positively associated with age, haemoglobin and parity at first antenatal visit. Maternal obesity was associated with increased likelihood of having high birthweight (aOR 2.54, 95% CI 1.39-4.66) and large size for gestational age (aOR 1.66, 95% CI 1.20-2.31) infants. In the subset cohort, GWG was associated with increased likelihood of spontaneous preterm delivery (aOR 4.35, 95% CI 1.55-12.21) and high birthweight (aOR 3.00, 95% CI 1.22-7.34) infants. CONCLUSION: Obesity during pregnancy is prevalent in this setting and appears associated with increased risk of adverse birth outcomes in both HIV-infected and HIV-uninfected women. Weight management interventions targeting women of child-bearing age are needed to promote healthy pregnancies and reduce adverse birth outcomes.

OBJECTIFS: Examiner l'association entre l'indice de masse corporelle maternelle (IMC) et le gain de poids gestationnel (GPG) et les résultats de naissance défavorables chez les femmes infectées et non infectées par le VIH. MÉTHODES: Dans une communauté urbaine sud-africaine, 2921 femmes enceintes consécutives infectées et non infectées par le VIH visitant les services de soins de santé primaires ont été évaluées lors de leur première visite prénatale. Un sous-ensemble de femmes infectées par le VIH inscrites à une étude longitudinale a été évalué trois fois pendant la grossesse. Toutes les femmes avaient des données sur les résultats à la naissance provenant des dossiers médicaux et des questionnaires d'étude. Dans les analyses, les associations entre l'IMC, le GPG, les facteurs maternels et les résultats de naissance défavorables ont été évalués en utilisant des modèles de régression logistique. RÉSULTATS: L'IMC médian estimé avant la grossesse était globalement de 29 kg/m2 (IQR, 24-34) pour les femmes non infectées par le VIH et 28 kg/m2 (IQR, 24 -34) pour celles infectées par le VIH; La prévalence du VIH était de 38%. Dans les modèles ajustés, l'augmentation de l'IMC dans la cohorte globale était positivement associée à l'âge, à l'hémoglobine et à la parité lors de la première visite prénatale. L'obésité maternelle a été associée à une augmentation de la probabilité d'avoir un nourrisson avec un poids élevé à la naissance (ORa 2,54, IC95%: 1,39-4,66) et une grande taille pour l'âge gestationnel (ORa 1,66, IC95%: 1,20-2,31). Dans la cohorte du sous-ensemble, le GPG était associé à une probabilité accrue d'accouchement prématuré spontané (aOR 4,35, IC95%: 1,55-12,21) et à des nourrissons avec un poids de naissance élevé (aOR 3,00, IC95%: 1,22-7,34). CONCLUSION: L'obésité pendant la grossesse est répandue dans ce contexte et semble associée à un risque accru d'accouchements défavorables chez les femmes infectées et non infectées par le VIH. Des interventions de prise en charge du poids ciblant les femmes en âge de procréer sont nécessaires pour promouvoir des grossesses saines et réduire les issues de naissance défavorables.

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.

The role of place of residency in childhood immunisation coverage in Nigeria: analysis of data from three DHS rounds 2003-2013.

BACKGROUND: In 2017, about 20% of the world's children under 1 year of age with incomplete DPT vaccination lived in Nigeria. Fully-immunised child coverage (FIC), which is the percentage of children aged 12-23 months who received all doses of routine infant vaccines in their first year of life in Nigeria is low. We explored the associations between child, household, community and health system level factors and FIC, in particular focussing on urban formal and slum, and rural residence, using representative Nigeria Demographic Health Survey (NDHS) data from 2003, 2008 and 2013. METHOD: Multilevel logistic regression models were applied for quantitative analyses of NDHS 2003, 2008 and 2013 data, singly, pooled overall and stratified by rural/urban, and within urban by formal and slum. We also quantify Population Attributable Risk (PAR) of FIC. RESULTS: FIC for rural, urban formal and slum rose from 7.4, 25.6 and 24.9% respectively in 2003 to 15.8, 45.5 and 38.5% in 2013, and varied across sociodemographics. In pooled NDHS analysis, overall and stratified, final FIC adjusted odds (aOR) were: 1. Total population - delivery place (health facility vs home, aOR = 1.13, 95% CI = 0.73-1.73), maternal education (higher vs no education, aOR = 3.92, 95% CI = 1.79-8.59) and place of residence (urban vs rural, aOR = 1.69, 95% CI = 0.89-3.22). 2. Rural, urban formal and slum stratified: A.Rural - delivery place (aOR = 1.47, 95% CI = 1.12-1.94), maternal education (aOR = 4.99, 95% CI = 2.48-10.06). B.Urban formal - delivery place (aOR = 2.62, 95% CI = 1.43-4.79), maternal education level (aOR = 9.18, 95% CI = 3.05-27.64). C.Slums - delivery place (aOR = 5.39, 95% CI = 2.18-13.33), maternal education (aOR = 5.03, 95% CI = 1.52-16.65). The PAR revealed the highest percentage point increase in FIC would be achieved in all places of residence by maternal higher education: rural-38.15, urban formal-22.88 and slum 23.76, while non-attendance of antenatal care was estimated to lead to the largest reduction in FIC. CONCLUSION: Although low FIC in rural areas may be largely due to lack of health facilities and immunisation education, the intra-urban disparity is mostly unexplained, and requires further qualitative and interventional research. We show the FIC point increase that can be achieved if specific sociodemographic variable (risk) are addressed in the various communities, thus informing prioritisation of interventions.

Breastfeeding, HIV exposure, childhood obesity, and prehypertension: A South African cohort study.

BACKGROUND: Evidence on the association between breastfeeding and later childhood obesity and blood pressure (BP) is inconsistent, especially in HIV-prevalent areas where, until recently, HIV-infected women were discouraged from breastfeeding, but obesity is increasingly prevalent. METHODS AND FINDINGS: The Siyakhula cohort (2012-2014), a population-based prospective cohort study, collected data over 3 visits on HIV-negative children ages 7 to 11 years in rural South Africa. We used weight (body mass index [BMI]), fat, and BP as outcome variables and incorporated early life (including mother's age at delivery and HIV status) and current life factors (including maternal education and current BMI). Our primary exposure was breastfeeding duration. We dichotomized 3 outcome measures using pre-established thresholds for clinical interpretability: (1) overfat: ≥85th percentile of body fat; (2) overweight: >1 SD BMI z score; and (3) prehypertension: ≥90th percentile for systolic BP (SBP) or diastolic BP (DBP). We modelled each outcome using multivariable logistic regression, including stopping breastfeeding, then early life, and finally current life factors. Of 1,536 children (mean age = 9.3 years; 872 girls; 664 boys), 7% were overfat, 13.2% overweight, and 9.1% prehypertensive. Over half (60%) of the mothers reported continued breastfeeding for 12+ months. In multivariable analyses, continued breastfeeding between 6 and 11 months was associated with approximately halved odds of both being overfat (adjusted odds ratio [aOR] = 0.43, 95% confidence interval [CI] 0.21-0.91, P = 0.027) and overweight (aOR = 0.46, CI 0.26-0.82, P = 0.0083), but the association with prehypertension did not reach statistical significance (aOR = 0.72, CI 0.38-1.37, P = 0.32). Children with a mother who was currently obese were 5 times more likely (aOR = 5.02, CI 2.47-10.20, P < 0.001) to be overfat and over 4 times more likely to be overweight (aOR = 4.33, CI 2.65-7.09, P < 0.001) than children with normal weight mothers. Differences between HIV-exposed and unexposed children on any of the outcomes were minimal and not significant. The main study limitation was that duration of breastfeeding was based on maternal recall. CONCLUSIONS: To our knowledge, this is the first study examining and quantifying the association between breastfeeding and childhood obesity in an African setting with high HIV prevalence. We observed that breastfeeding was independently associated with reduced childhood obesity for both HIV-exposed and unexposed children, suggesting that promoting optimal nutrition throughout the life course, starting with continued breastfeeding, may be critical to tackling the growing obesity epidemic. In the era of widespread effective antiretroviral treatment for HIV-infected women for life, these data further support the recommendation of breastfeeding for all women.

Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies.

Background: Human immunodeficiency virus (HIV)-infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" were used to estimate the relative contribution of risk factors to overall mortality. Results: Cumulative incidence of death was 5.5% (95% confidence interval, 5.1-5.9) by age 24 months. Low birth weight (LBW <2500 g, adjusted hazard ratio (aHR, 2.9), no breastfeeding (aHR, 2.5), and maternal death (aHR, 11.1) were significantly associated with increased mortality. Maternal ART (aHR, 0.5) was significantly associated with lower mortality. At the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions: Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates.

The immune response to sub-clinical mastitis is impaired in HIV-infected women.

BACKGROUND: Subclinical mastitis (SCM) is relatively common in lactating women and may be associated with HIV shedding in breast milk. The potential association between HIV infection and breast milk immunologic factors and immune response to SCM needs to be addressed. METHODS: In this cross-sectional study, SCM (Na/K ratio > 1) was tested in 165 mature breast milk samples collected from 40 HIV-infected women who didn't transmit HIV to their child by breastfeeding and 43 HIV-uninfected women enrolled in an interventional cohort in South-Africa (Vertical Transmission Study). The level of 33 immune markers related to Th1/Th2 related response, inflammation and bacterial exposure were compared in ART-naive HIV-infected versus HIV-uninfected women. The associations between HIV infection and SCM on the concentration of immune factors were tested separately by Wilcoxon rank-sum test and corrected for false discovery rate. To control for potential confounder effects and take into account the clustering of breast milk samples from a single woman, multivariate mixed linear models adjusted on child age at the time of sampling were performed for each immune factor. RESULTS: Subclinical mastitis was detected in 15 (37.5%) HIV-infected women and 10 (23.3%) HIV-uninfected women. In the absence of SCM, the breast milk levels of IP-10 and MIG were higher and IL1-RA lower in HIV-infected women than in HIV-uninfected women (respectively p < 0.001, p = 0.001, p = 0.045). In HIV-uninfected women, SCM was characterized by a robust immune response with higher concentrations of a broad panel of Th1 and inflammatory related immune markers than in samples without SCM. By contrast, in HIV-infected women a limited number of immune markers were increased and lower increases were observed in samples with SCM than without SCM. CONCLUSION: HIV infection in ART-naïve women was associated with elevated breast milk levels of IP-10 and MIG, which areTh1-related cytokines induced by IFN-γ. During SCM, a lower and narrower immune response was observed in HIV-infected than HIV-uninfected women, suggesting that HIV infection affects the capacity of the mammary gland to respond to SCM.

Viraemia before, during and after pregnancy in HIV-infected women on antiretroviral therapy in rural KwaZulu-Natal, South Africa, 2010-2015.

OBJECTIVES: Pregnancy and post-partum viral load suppression is critical to prevent mother-to-child HIV transmission and ensure maternal health. We measured viraemia risk before, during and after pregnancy in HIV-infected women. METHODS: Between 2010 and 2015, 1425 HIV-infected pregnant women on lifelong antiretroviral therapy (ART) for at least six months pre-pregnancy were enrolled in a cohort study in rural KwaZulu-Natal, South Africa. Odds ratios were estimated in multilevel logistic regression, with pregnancy period time-varying. RESULTS: Over half of 1425 women received tenofovir-based regimens (n = 791). Median pre-pregnancy ART duration was 2.1 years. Of 988 women (69.3%) with pre-pregnancy viral loads, 82.0%, 6.8% and 11.2% had VL <50, 50-999 and ≥1000 copies/ml, respectively. During pregnancy and at six, 12 and 24 months, viral load was ≥1000 copies/ml in 15.2%, 15.7%, 17.8% and 16.6% respectively; viral load <50 was 76.9%, 77%, 75.5% and 75.8%, respectively. Adjusting for age, clinical and pregnancy factors, viraemia risk (viral load ≥50 copies/ml) was not significantly associated with pregnancy [adjusted OR (aOR) 1.31; 95% CI 0.90-1.92], six months (aOR 1.30; 95% CI 0.83-2.04), 12 months (aOR 0.96; 95% CI 0.58-1.58) and 24 months (aOR 1.40; 95% CI 0.89-2.22) post-partum. Adjusting for ART duration-pregnancy period interaction, viraemia risk was 1.8 during pregnancy and twofold higher post-partum. CONCLUSIONS: While undetectable viral load before pregnancy through post-partum was common, the UNAIDS goal to suppress viraemia in 90% of women was not met. Women on preconception ART remain vulnerable to viraemia; additional support is required to prevent mother-to-child HIV transmission and maintain maternal health.

Socio-economic differentials in minimum dietary diversity among young children in South-East Asia: evidence from Demographic and Health Surveys.

OBJECTIVE: To investigate the socio-economic differentials underlying minimum dietary diversity (MDD) among children aged 6-23 months in three economically diverse South-East Asian countries. DESIGN: The outcome variable MDD was defined as the proportion of children aged 6-23 months who received foods from four of the seven recommended food groups within the 24 h prior to interview. The association between socio-economic factors and MDD, adjusting for relevant characteristics, was examined using logistic regression. SETTING: We used cross-sectional population data from recent Demographic and Health Surveys from Cambodia (2014), Myanmar (2015-16) and Indonesia (2012). SUBJECTS: Total of 8364 children aged 6-23 months. RESULTS: Approximately half of all children met the MDD, varying from 47·7 % in Cambodia (n 1023) to 58·2 % in Indonesia (n 2907) and 24·6 % in Myanmar (n 301). The likelihood (adjusted OR; 95 % CI) of meeting MDD increased for children in the richest households (Cambodia: 2·4; 1·7, 3·4; Myanmar: 1·8; 1·1, 3·0; Indonesia: 2·0; 1·6, 2·5) and those residing in urban areas (Cambodia: 1·4; 1·1, 1·9; Myanmar: 1·7; 1·2, 2·4; Indonesia: 1·7; 1·5, 1·9). MDD deprivation was most severe among children from the poorest households in rural areas. The association between mother's labour force participation and MDD was positive in all three countries but reached significance only in Indonesia (1·3; 1·1, 1·5). CONCLUSIONS: MDD deprivation among young children was significantly high in socio-economically disadvantaged families in all three study settings. MDD requirements are not being met for approximately half of young children in these three South-East Asian countries.

Impact of Point-of-Care Xpert MTB/RIF on Tuberculosis Treatment Initiation. A Cluster-randomized Trial.

RATIONALE: Point-of-care (POC) diagnostics have the potential to reduce pretreatment loss to follow-up and delays to initiation of appropriate tuberculosis (TB) treatment. OBJECTIVES: To evaluate the effect of a POC diagnostic strategy on initiation of appropriate TB treatment. METHODS: We conducted a cluster-randomized trial of adults with cough who were HIV positive and/or at high risk of drug-resistant TB. Two-week time blocks were randomized to two strategies: (1) Xpert MTB/RIF test (Cepheid, Sunnyvale, CA) performed at a district hospital laboratory or (2) POC Xpert MTB/RIF test performed at a primary health care clinic. All participants provided two sputum specimens: one for the Xpert test and the other for culture as a reference standard. The primary outcome was the proportion of participants with culture-positive pulmonary tuberculosis (PTB) initiated on appropriate TB treatment within 30 days. MEASUREMENTS AND MAIN RESULTS: Between August 22, 2011, and March 1, 2013, 36 two-week blocks were randomized, and 1,297 individuals were enrolled (646 in the laboratory arm, 651 in the POC arm), 159 (12.4%) of whom had culture-positive PTB. The proportions of participants with culture-positive PTB initiated on appropriate TB treatment within 30 days were 76.5% in the laboratory arm and 79.5% in the POC arm (odds ratio, 1.13; 95% confidence interval, 0.51-2.53; P = 0.76; risk difference, 3.1%; 95% confidence interval, -16.2 to 10.1). The median time to initiation of appropriate treatment was 7 days (laboratory) versus 1 day (POC). CONCLUSIONS: POC positioning of the Xpert test led to more rapid initiation of appropriate TB treatment. Achieving one-stop diagnosis and treatment for all people with TB will require simpler, more sensitive diagnostics and broader strengthening of health systems. Clinical trial registered with www.isrctn.com (ISRCTN 18642314) and www.sanctr.gov.za (DOH-27-0711-3568).

Towards control of the global HIV epidemic: Addressing the middle-90 challenge in the UNAIDS 90-90-90 target.

In a Perspective, Collins Iwuji and Marie-Louise Newell discuss early findings from Richard Hayes and colleagues' PopART study on HIV testing and treatment.

Under-five mortality according to maternal survival: a systematic review and meta-analysis.

OBJECTIVE: To investigate, within so-called general populations, the relationship between maternal survival and mortality of children younger than five years. METHODS: We conducted a systematic review of literature published between January 1990 and November 2016 that reported maternal vital status and the corresponding mortality of children younger than five years. Seven studies were included in a qualitative analysis and four in a random-effects meta-analysis. Summary estimates of the odds of dying by maternal survival were obtained and statistical heterogeneity estimated. Quality of the included studies and evidence was assessed using a Cochrane tool for assessing risk of bias and the Grading of Recommendations Assessment, Development and Evaluation criteria, respectively. FINDINGS: Among children younger than five years, those whose mother had died were found to be 4.09 times (95% confidence interval, CI: 2.40-6.98) more likely to die than those with surviving mothers. Due to heterogeneity (I2: 83%), further pooled estimates were not possible. For children that were motherless as a result of maternal mortality, the increased odds of dying ranged from 1.40 (95% CI: 0.47-4.21) to 2.92 (95% CI: 1.21-7.04) among those aged between two and four years, 6.1 (95% CI: 2.27-16.77) to 33.78 (95% CI: 24.21-47.14) for those younger than one year and 4.39 (95% CI: 3.34-5.78) to 51.68 (95% CI: 20.26-131.80) for those younger than six months. CONCLUSION: The loss of a mother was associated with increased mortality among children, especially when maternal death occurred in the first year of the child's life.

Formula-Feeding of HIV-Exposed Uninfected African Children Is Associated with Faster Growth in Length during the First 6 Months of Life in the Kesho Bora Study.

Background: Early feeding patterns may affect the growth of HIV-exposed children and thus their subsequent health and cognition.Objective: We assessed the association of infant feeding (IF) mode with length-for-age z score (LAZ) and stunting from age 2 d to 18 mo in HIV-exposed African children within a controlled randomized trial, which evaluated triple antiretrovirals initiated during pregnancy and continued for 6 mo postpartum to prevent HIV transmission.Methods: HIV-infected pregnant women with CD4+ counts of 200-500 cells/mm3 from Burkina Faso, Kenya, and South Africa were advised to exclusively breastfeed for up to 6 mo or to formula-feed from birth. Factors associated with LAZ were investigated in all uninfected children by using mixed-effects linear models; those associated with stunting (LAZ <-2) at 6 or 12 mo were assessed in multiple logistic regression after exclusion of children stunted at age 2 d. Independent variables were IF mode: formula feeding (FF), exclusive breastfeeding (EBF) <3 mo, or EBF ≥3 mo (reference); sex; trial arm; maternal characteristics; and site.Results: Among 728 children, FF was associated with a greater increase in LAZ from 2 d to 6 mo (+0.07 z score/mo, P < 0.001). Between 6 and 18 mo, FF and EBF <3 mo were both associated with greater mean LAZ than was EBF ≥3 mo (+0.52 z scores and +0.43 z scores, respectively, P < 0.001). Among children not stunted at 2 d, FF was independently associated with a reduced risk of stunting at 6 mo (OR: 0.24; 95% CI: 0.07, 0.81; P = 0.021), whereas EBF <3 mo was not (OR: 0.49; 95% CI: 0.22, 1.10; P = 0.09).Conclusions: In this observational study of HIV-exposed uninfected infants, growth in length in the first 6 mo of life was faster in formula-fed infants than in exclusively breastfed infants. The plausibility of residual confounding and reverse causality is discussed. This trial was registered at www.controlled-trials.com as ISRCTN71468401.

Subclinical mastitis occurs frequently in association with dramatic changes in inflammatory/anti-inflammatory breast milk components.

BACKGROUND: Subclinical mastitis (SCM) is a frequent, but poorly characterized entity that may influence immune development of breastfed infants. Mechanisms driving the emergence of SCM and changes in immunological content of human milk during SCM remain to be explored. In this study, the breast milk environment was to describe during SCM. METHODS: One hundred and ten samples of mature breast milk were collected from 44 healthy, HIV-negative mothers, included in a large infant feeding intervention cohort (ANRS 1271/Vertical Transmission Study). Immune markers related to inflammatory/anti-inflammatory balances and secreted in response to bacterial exposure were explored in SCM breast milk samples (Na/K ratio > 1) and compared to non-SCM controls. RESULTS: SCM was observed in 23% of women (95% confidence interval (CI): 21-24) and associated with higher levels of inflammatory markers (ß2 microgobulin, PS100A9, TNF-α, IL-6, IL-8, IL-17, and RANTES) and Th1-related cytokines (IL-2R, IL-12p40/70, IFN-α, IFN-γ, CXCL-9, andIP-10). High levels of factors secreted in response to bacteria and lipopolysaccharide (LPS) exposure were observed in SCM breast milk samples (MIP-1α, MIP-1ß, LPS binding protein, α-defensins, and antileukoproteinase 1). CONCLUSION: SCM is associated with important changes in breast milk microenvironment, with a proinflammatory/Th1-cytokine predominant profile. During SCM, cytokine imbalances in breast milk may have a notable influence on mucosal immune system of the infant early in life.

Exclusive Breastfeeding and Cognition, Executive Function, and Behavioural Disorders in Primary School-Aged Children in Rural South Africa: A Cohort Analysis.

BACKGROUND: Exclusive breastfeeding (EBF) is associated with early child health; its longer-term benefits for child development remain inconclusive. We examine the associations between EBF, HIV exposure, and other maternal/child factors and the cognitive and emotional-behavioural development of children aged 7-11 y. METHODS AND FINDINGS: The Vertical Transmission Study (VTS) supported EBF in HIV-positive and HIV-negative women; between 2012 and 2014, HIV-negative VTS children (332 HIV exposed, 574 HIV unexposed) were assessed in terms of cognition (Kaufman Assessment Battery for Children Second Edition [KABC-II]), executive function (Developmental Neuropsychological Assessment Second Edition [NEPSY-II]), and emotional-behavioural functioning (parent-reported Child Behaviour Checklist, [CBCL]). We developed population means by combining the VTS sample with 629 same-aged HIV-negative children from the local demographic platform. For each outcome, we split the VTS sample into scores above or at/below each population mean and modelled each outcome using logistic regression analyses, overall and stratified by child sex. There was no demonstrated effect of EBF on overall cognitive functioning. EBF was associated with fewer conduct disorders overall (adjusted odds ratio [aOR] 0.44 [95% CI 0.3-0.7], p ≤ 0.01), and there was weak evidence of better cognition in boys who had been exclusively breastfed for 2-5 mo versus ≤1 mo (Learning subscale aOR 2.07 [95% CI 1.0-4.3], p = 0.05). Other factors associated with better child cognition were higher maternal cognitive ability (aOR 1.43 [95% CI 1.1-1.9], p = 0.02, Sequential; aOR 1.74 [95% CI 1.3-2.4], p < 0.001, Planning subscales) and crèche attendance (aOR 1.96 [95% CI 1.1-3.5], p = 0.02, Sequential subscale). Factors positively associated with executive function were home stimulation (aOR 1.36 [95% CI 1.0-1.8], p = 0.04, Auditory Attention; aOR 1.35 [95% CI 1.0-1.8], p = 0.05, Response Set) and crèche (aOR 1.74 [95% CI 1.0-3.0], p = 0.05, Animal Sorting). Maternal mental health problems and parenting stress were associated with increased emotional-behavioural problems on the total CBCL (aOR 2.44 [95% CI 1.3-4.6], p = 0.01; aOR 7.04 [95% CI 4.2-11.9], p < 0.001, respectively). Maternal HIV status was not associated with any outcomes in the overall cohort. Limitations include the nonrandomised study design and lack of maternal mental health assessment at the child's birth. CONCLUSIONS: EBF was associated with fewer than average conduct disorders and weakly associated with improved cognitive development in boys. Efforts to improve stimulation at home, reduce maternal stress, and enable crèche attendance are likely to improve executive function and emotional-behavioural development of children.