The Association Between Breastfeeding and Growth Among Infants with Moderately Low Birth Weight: A Prospective Cohort Study.

OBJECTIVE: To assess the association between breastfeeding competency, as determined by Latch, Audible swallowing, Type of nipple, Comfort, and Hold (LATCH) and Preterm Infant Breastfeeding Behavior Scale (PIBBS) scores, and exclusive breastfeeding and growth among infants with low birth weight (LBW) in India, Malawi, and Tanzania. STUDY DESIGN: We conducted LATCH and PIBBS assessments among mother-infant dyads enrolled in the Low Birthweight Infant Feeding Exploration (LIFE) observational study of infants with moderately LBW (1500g-2499 g) in India, Malawi, and Tanzania. We analyzed feeding and growth patterns among this cohort. RESULTS: We observed 988 infants. We found no association between LATCH or PIBBS scores and rates of exclusive breastfeeding at 4 or 6 months. Higher week 1 LATCH and PIBBS scores were associated with increased likelihood of regaining birth weight by 2 weeks of age [LATCH: aRR 1.42 (95% CI 1.15, 1.76); PIBBS: aRR 1.15 (95% CI 1.07, 1.23); adjusted for maternal age, parity, education, residence, delivery mode, LBW type, number of offspring, and site]. Higher PIBBS scores at 1 week were associated with improved weight gain velocity (weight-for-age z-score change) at 1, 4, and 6 months [adjusted beta coefficient: 1 month 0.04 (95% CI 0.01, 0.06); 4 month 0.04 (95% CI 0.01, 0.06); and 6 month 0.04 (95% CI 0.00, 0.08)]. CONCLUSION: Although week 1 LATCH and PIBBS scores were not associated with rates of exclusive breastfeeding, higher scores were positively associated with growth metrics among infants with LBW, suggesting that these tools may be useful to identify dyads who would benefit from early lactation support.

Lessons learned in implementing the Low Birthweight Infant Feeding Exploration study: A large, multi-site observational study.

OBJECTIVE: Globally, early and optimal feeding practices and strategies for small and vulnerable infants are limited. We aim to share the challenges faced and implementation lessons learned from a complex, mixed methods research study on infant feeding. DESIGN: A formative, multi-site, observational cohort study using convergent parallel, mixed-methods design. SETTING: Twelve tertiary/secondary, public/private hospitals in India, Malawi and Tanzania. POPULATION OR SAMPLE: Moderately low birthweight infants (MLBW; 1.50-2.49 kg). METHODS: We assessed infant feeding and care practices through: (1) assessment of in-facility documentation of 603 MLBW patient charts; (2) intensive observation of 148 MLBW infants during facility admission; and (3) prospective 1-year follow-up of 1114 MLBW infants. Focus group discussions and in-depth interviews gathered perspectives on infant feeding among clinicians, families, and key stakeholders. MAIN OUTCOME MEASURES: The outcomes of the primary study were: (1) To understand the current practices and standard of care for feeding LBW infants; (2) To define and document the key outcomes (including growth, morbidity, and lack of success on mother's own milk) for LBW infants under current practices; (3) To assess the acceptability and feasibility of a system-level Infant and Young Child Feeding (IYCF) intervention and the proposed infant feeding options for LBW infants. RESULTS: Hospital-level guidelines and provision of care for MLBW infants varied across and within countries. In all, 89% of charts had missing data on time to first feed and 56% lacked discharge weights. Among 148 infants observed in-facility, 18.5% were discharged prior to meeting stated weight goals. Despite challenges during COVID, 90% of the prospective cohort was followed until 12 months of age. CONCLUSIONS: Enrolment and follow-up of this vulnerable population required additional effort from researchers and the community. Using a mixed-methods exploratory study allowed for a comprehensive understanding of MLBW health and evidence-based planning of targeted large-scale interventions. Multi-site partnerships in global health research, which require active and equal engagement, are instrumental in avoiding duplication and building a stronger, generalisable evidence base.

A rapid landscape review of postpartum anaemia measurement: challenges and opportunities.

BACKGROUND: Anaemia is a reduction in haemoglobin concentration below a threshold, resulting from various factors including severe blood loss during and after childbirth. Symptoms of anaemia include fatigue and weakness, among others, affecting health and quality of life. Anaemic pregnant women have an increased risk of premature delivery, a low-birthweight infant, and postpartum depression. They are also more likely to have anaemia in the postpartum period which can lead to an ongoing condition and affect subsequent pregnancies. In 2019 nearly 37% of pregnant women globally had anaemia, and estimates suggest that 50-80% of postpartum women in low- and middle-income countries have anaemia, but currently there is no standard measurement or classification for postpartum anaemia. METHODS: A rapid landscape review was conducted to identify and characterize postpartum anaemia measurement searching references within three published systematic reviews of anaemia, including studies published between 2012 and 2021. We then conducted a new search for relevant literature from February 2021 to April 2022 in EMBASE and MEDLINE using a similar search strategy as used in the published reviews. RESULTS: In total, we identified 53 relevant studies. The timing of haemoglobin measurement ranged from within the immediate postpartum period to over 6 weeks. The thresholds used to diagnose anaemia in postpartum women varied considerably, with < 120, < 110, < 100 and < 80 g/L the most frequently reported. Other laboratory results frequently reported included ferritin and transferrin receptor. Clinical outcomes reported in 32 out of 53 studies included postpartum depression, quality of life, and fatigue. Haemoglobin measurements were performed in a laboratory, although it is unclear from the studies if venous samples and automatic analysers were used in all cases. CONCLUSIONS: This review demonstrates the need for improving postpartum anaemia measurement given the variability observed in published measures. With the high prevalence of anaemia, the relatively simple treatment for non-severe cases of iron deficiency anaemia, and its importance to public health with multi-generational effects, it is crucial to develop common measures for women in the postpartum period and promote rapid uptake and reporting.

Components of clean delivery kits and newborn mortality in the Zambia Chlorhexidine Application Trial (ZamCAT): An observational study.

BACKGROUND: Neonatal infection, a leading cause of neonatal death in low- and middle-income countries, is often caused by pathogens acquired during childbirth. Clean delivery kits (CDKs) have shown efficacy in reducing infection-related perinatal and neonatal mortality. However, there remain gaps in our current knowledge, including the effect of individual components, the timeline of protection, and the benefit of CDKs in home and facility deliveries. METHODS AND FINDINGS: A post hoc secondary analysis was performed using nonrandomized data from the Zambia Chlorhexidine Application Trial (ZamCAT), a community-based, cluster-randomized controlled trial of chlorhexidine umbilical cord care in Southern Province of Zambia from February 2011 to January 2013. CDKs, containing soap, gloves, cord clamps, plastic sheet, razor blade, matches, and candle, were provided to all pregnant women. Field monitors made a home-based visit to each participant 4 days postpartum, during which CDK use and newborn outcomes were ascertained. Logistic regression was used to study the association between different CDK components and neonatal mortality rate (NMR). Of 38,579 deliveries recorded during the study, 36,996 newborns were analyzed after excluding stillbirths and those with missing information. Gloves, cord clamps, and plastic sheets were the most frequently used CDK item combination in both home and facility deliveries. Each of the 7 CDK components was associated with lower NMR in users versus nonusers. Adjusted logistic regression showed that use of gloves (odds ratio [OR] 0.33, 95% CI 0.24-0.46), cord clamp (OR 0.51, 95% CI 0.38-0.68), plastic sheet (OR 0.46, 95% CI 0.34-0.63), and razor blade (OR 0.69, 95% CI 0.53-0.89) were associated with lower risk of newborn mortality. Use of gloves and cord clamp were associated with reduced risk of immediate newborn death (<24 hours). Reduction in risk of early newborn death (1-6 days) was associated with use of gloves, cord clamps, plastic sheets, and razor blades. In examining perinatal mortality (stillbirth plus neonatal death in the first 7 days of life), similar patterns were observed. There was no significant reduction in risk of late newborn mortality (7-28 days) with CDK use. Study limitations included potential recall bias of CDK use and inability to establish causality, as this was a secondary observational study. CONCLUSIONS: CDK use was associated with reductions in early newborn mortality at both home and facility deliveries, especially when certain kit components were used. While causality could not be established in this nonrandomized secondary analysis, given these beneficial associations, scaling up the use of CDKs in rural areas of sub-Saharan Africa may improve neonatal outcomes. TRIAL REGISTRATION: Name of trial: Zambia Chlorhexidine Application Trial (ZamCAT) Name of registry: Clinicaltrials.gov Trial number: NCT01241318.

Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.

BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa. METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes. CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths. TRIAL REGISTRATION: The study is not a clinical trial.

Operationalizing respectful maternity care at the healthcare provider level: a systematic scoping review.

BACKGROUND: Ensuring the right to respectful care for maternal and newborn health, a critical dimension of quality and acceptability, requires meeting standards for Respectful Maternity Care (RMC). Absence of mistreatment does not constitute RMC. Evidence generation to inform definitional standards for RMC is in an early stage. The aim of this systematic review is clear provider-level operationalization of key RMC principles, to facilitate their consistent implementation. METHODS: Two rights-based frameworks define the underlying principles of RMC. A qualitative synthesis of both frameworks resulted in seven fundamental rights during childbirth that form the foundation of RMC. To codify operational definitions for these key elements of RMC at the healthcare provider level, we systematically reviewed peer-reviewed literature, grey literature, white papers, and seminal documents on RMC. We focused on literature describing RMC in the affirmative rather than mistreatment experienced by women during childbirth, and operationalized RMC by describing objective provider-level behaviors. RESULTS: Through a systematic review, 514 records (peer-reviewed articles, reports, and guidelines) were assessed to identify operational definitions of RMC grounded in those rights. After screening and review, 54 records were included in the qualitative synthesis and mapped to the seven RMC rights. The majority of articles provided guidance on operationalization of rights to freedom from harm and ill treatment; dignity and respect; information and informed consent; privacy and confidentiality; and timely healthcare. Only a quarter of articles mentioned concrete or affirmative actions to operationalize the right to non-discrimination, equality and equitable care; less than 15%, the right to liberty and freedom from coercion. Provider behaviors mentioned in the literature aligned overall with seven RMC principles; yet the smaller number of available research studies that included operationalized definitions for some key elements of RMC illustrates the nascent stage of evidence-generation in this area. CONCLUSIONS: Lack of systematic codification, grounded in empirical evidence, of operational definitions for RMC at the provider level has limited the study, design, implementation, and comparative assessment of respectful care. This qualitative systematic review provides a foundation for maternity healthcare professional policy, training, programming, research, and program evaluation aimed at studying and improving RMC at the provider level.

Respectful care for mothers and newborns is a right and important part of ensuring that their care is high quality and acceptable to them. Just because there is no mistreatment does not mean that Respectful Maternity Care (RMC) was given. Without a clear framework for provider behaviors that reflect RMC principles, it is hard to ensure every woman and newborn gets respectful care in practice. We compared and combined two frameworks summarizing maternal and newborn rights and came out with seven categories. Then we searched for articles that mentioned provider behaviors reflecting RMC. We found 514 articles and ended up with 54 after careful review, from which we pulled the observable behaviors for providers in each category. Almost all papers mentioned actions to protect women and newborns from harm and mistreatment, to treat them with dignity and respect, and to give information and respect choices. About half of papers mentioned actions to protect privacy and to make sure every mother and newborn gets care when needed. Only 25% of papers mentioned actions to make sure all women and newborns receive equal care, and only 15% included actions to make sure women and newborns are physically free to leave facilities at will, and get care whether or not they can pay. This framework defining RMC behaviors for providers is based on data from many studies and can be useful to look at whether maternal newborn care in facilities meets these standards and to inform training and more research to improve RMC.

The effect of milk type and fortification on the growth of low-birthweight infants: An umbrella review of systematic reviews and meta-analyses.

Approximately 15% of infants worldwide are born with low birthweight (<2500 g). These children are at risk for growth failure. The aim of this umbrella review is to assess the relationship between infant milk type, fortification and growth in low-birthweight infants, with particular focus on low- and lower middle-income countries. We conducted a systematic review in PubMed, CINAHL, Embase and Web of Science comparing infant milk options and growth, grading the strength of evidence based on standard umbrella review criteria. Twenty-six systematic reviews qualified for inclusion. They predominantly focused on infants with very low birthweight (<1500 g) in high-income countries. We found the strongest evidence for (1) the addition of energy and protein fortification to human milk (donor or mother's milk) leading to increased weight gain (mean difference [MD] 1.81 g/kg/day; 95% confidence interval [CI] 1.23, 2.40), linear growth (MD 0.18 cm/week; 95% CI 0.10, 0.26) and head growth (MD 0.08 cm/week; 95% CI 0.04, 0.12) and (2) formula compared with donor human milk leading to increased weight gain (MD 2.51 g/kg/day; 95% CI 1.93, 3.08), linear growth (MD 1.21 mm/week; 95% CI 0.77, 1.65) and head growth (MD 0.85 mm/week; 95% CI 0.47, 1.23). We also found evidence of improved growth when protein is added to both human milk and formula. Fat supplementation did not seem to affect growth. More research is needed for infants with birthweight 1500-2500 g in low- and lower middle-income countries.

Outcomes of a Coaching-Based WHO Safe Childbirth Checklist Program in India.

BACKGROUND: The prevalence of facility-based childbirth in low-resource settings has increased dramatically during the past two decades, yet gaps in the quality of care persist and mortality remains high. The World Health Organization (WHO) Safe Childbirth Checklist, a quality-improvement tool, promotes systematic adherence to practices that have been associated with improved childbirth outcomes. METHODS: We conducted a matched-pair, cluster-randomized, controlled trial in 60 pairs of facilities across 24 districts of Uttar Pradesh, India, testing the effect of the BetterBirth program, an 8-month coaching-based implementation of the Safe Childbirth Checklist, on a composite outcome of perinatal death, maternal death, or maternal severe complications within 7 days after delivery. Outcomes - assessed 8 to 42 days after delivery - were compared between the intervention group and the control group with adjustment for clustering and matching. We also compared birth attendants' adherence to 18 essential birth practices in 15 matched pairs of facilities at 2 and 12 months after the initiation of the intervention. RESULTS: Of 161,107 eligible women, we enrolled 157,689 (97.9%) and determined 7-day outcomes for 157,145 (99.7%) mother-newborn dyads. Among 4888 observed births, birth attendants' mean practice adherence was significantly higher in the intervention group than in the control group (72.8% vs. 41.7% at 2 months; 61.7% vs. 43.9% at 12 months; P<0.001 for both comparisons). However, there was no significant difference between the trial groups either in the composite primary outcome (15.1% in the intervention group and 15.3% in the control group; relative risk, 0.99; 95% confidence interval, 0.83 to 1.18; P=0.90) or in secondary maternal or perinatal adverse outcomes. CONCLUSIONS: Birth attendants' adherence to essential birth practices was higher in facilities that used the coaching-based WHO Safe Childbirth Checklist program than in those that did not, but maternal and perinatal mortality and maternal morbidity did not differ significantly between the two groups. (Funded by the Bill and Melinda Gates Foundation; Clinical Trials number, NCT02148952 .).

Effectiveness of community outreach HIV prevention programs in Vietnam: a mixed methods evaluation.

BACKGROUND: In 2014, Vietnam was the first Southeast Asian country to commit to achieving the World Health Organization's 90-90-90 global HIV targets (90% know their HIV status, 90% on sustained treatment, and 90% virally suppressed) by 2020. This pledge represented further confirmation of Vietnam's efforts to respond to the HIV epidemic, one feature of which has been close collaboration with the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Starting in 2004, PEPFAR supported community outreach programs targeting high-risk populations (people who inject drugs, men who have sex with men, and sex workers). To provide early evidence on program impact, in 2007-2008 we conducted a nationwide evaluation of PEPFAR-supported outreach programs in Vietnam. The evaluation focused on assessing program effect on HIV knowledge, high-risk behaviors, and HIV testing among high-risk populations-results relevant to Vietnam's push to meet global HIV goals. METHODS: We used a mixed-methods cross-sectional evaluation design. Data collection encompassed a quantitative survey of 2199 individuals, supplemented by 125 in-depth interviews. Participants were members of high-risk populations who reported recent contact with an outreach worker (intervention group) or no recent contact (comparison group). We assessed differences in HIV knowledge, risky behaviors, and HIV testing between groups, and between high-risk populations. RESULTS: Intervention participants knew significantly more about transmission, prevention, and treatment than comparison participants. We found low levels of injection drug-use-related risk behaviors and little evidence of program impact on such behaviors. In contrast, a significantly smaller proportion of intervention than comparison participants reported risky sexual behaviors generally and within each high-risk population. Intervention participants were also more likely to have undergone HIV testing (76.1% vs. 47.0%, p < 0.0001) and to have received pre-test (78.0% vs. 33.7%, p < 0.0001) and post-test counseling (80.9% vs. 60.5%, p < 0.0001). Interviews supported evidence of high impact of outreach among all high-risk populations. CONCLUSIONS: Outreach programs appear to have reduced risky sexual behaviors and increased use of HIV testing services among high-risk populations in Vietnam. These programs can play a key role in reducing gaps in the HIV care cascade, achieving the global 90-90-90 goals, and creating an AIDS-free generation.

Availability of Safe Childbirth Supplies in 284 Facilities in Uttar Pradesh, India.

Objectives Vital to implementation of the World Health Organization (WHO) Safe Childbirth Checklist (SCC), designed to improve delivery of 28 essential birth practices (EBPs), is the availability of safe birth supplies: 22 EBPs on the SCC require one or more supplies. Mapping availability of these supplies can determine the scope of shortages and need for supply chain strengthening. Methods A cross-sectional survey on the availability of functional and/or unexpired supplies was assessed in 284 public-sector facilities in 38 districts in Uttar Pradesh, India. The twenty-three supplies were categorized into three non-mutually exclusive groups: maternal (8), newborn (9), and infection control (6). Proportions and mean number of supplies available were calculated; means were compared across facility types using t-tests and across districts using a one-way ANOVA. Log-linear regression was used to evaluate facility characteristics associated with supply availability. Results Across 284 sites, an average of 16.9 (73.5%) of 23 basic childbirth supplies were available: 63.4% of maternal supplies, 79.1% of newborn supplies, and 78.7% of infection control supplies. No facility had all 23 supplies available and only 8.5% had all four medicines assessed. Significant variability was observed by facility type and district. In the linear model, facility type and distance from district hospital were significant predictors of higher supply availability. Conclusions for Practice In Uttar Pradesh, more remote sites, and primary and community health centers, were at higher risk of supply shortages. Supply chain management must be improved for facility-based delivery and quality of care initiatives to reduce maternal and neonatal harm.

Can community health workers identify omphalitis? A validation study from Southern Province, Zambia.

OBJECTIVE: Omphalitis, or umbilical cord infection, is an important cause of newborn morbidity and mortality in low-resource settings. We tested an algorithm that task-shifts omphalitis diagnosis to community-level workers in sub-Saharan Africa. METHODS: Community-based field monitors and Zambian paediatricians independently evaluated newborns presenting to health facilities in Southern Zambia using a signs and symptoms checklist. Responses were compared against the paediatrician's gold standard clinical diagnosis. RESULTS: Of 1009 newborns enrolled, 6.2% presented with omphalitis per the gold standard clinical diagnosis. Paediatricians' signs and symptoms with the highest sensitivity were presence of pus (79.4%), redness at the base (50.8%) and newborn flinching when cord was palpated (33.3%). The field monitor's signs and symptoms answers had low correlation with paediatrician's answers; all signs and symptoms assessed had sensitivity <16%. CONCLUSION: Despite extensive training, field monitors could not consistently identify signs and symptoms associated with omphalitis in the sub-Saharan African setting.

Effectiveness of a WHO Safe Childbirth Checklist Coaching-based intervention on the availability of Essential Birth Supplies in Uttar Pradesh, India.

OBJECTIVE: Evaluate the impact of a World Health Organization Safe Childbirth Checklist coaching-based intervention (BetterBirth Program) on availability and procurement of essential childbirth-related supplies. DESIGN: Matched pair, cluster-randomized controlled trial. SETTING: Uttar Pradesh, India. PARTICIPANTS: 120 government-sector health facilities (60 interventions, 60 controls). Supply-availability surveys were conducted quarterly in all sites. Coaches collected supply procurement sources from intervention sites. INTERVENTIONS: Coaching targeting implementation of Checklist with data feedback and action planning. MAIN OUTCOME MEASURES: Mean supply availability by study arm; change in procurement sources for intervention sites. RESULTS: At baseline, 6 and 12 months, the intervention sites had a mean of 20.9 (95% confidence interval (CI): 20.2-21.5); 22.4 (95% CI: 21.8-22.9) and 22.1 (95% CI:21.4-22.8) items, respectively. Control sites had 20.8 (95% CI: 20.3-21.3); 20.9 (95% CI: 20.3-21.5) and 21.7 (95% CI: 20.8-22.6) items at the same time-points. There was a small but statistically significant higher availability in intervention sites at 6 months (difference-in-difference (DID) = 1.43, P < 0.001), which was not seen by 12 months (DID = 0.37, P = 0.53). Greater difference between intervention and control sites starting in the bottom quartile of supply availability was seen at 6 months (DID = 4.0, P = 0.0002), with no significant difference by 12 months (DID = 1.5, P = 0.154). No change was seen in procurement sources with ~5% procured by patients with some rates as high as 29% (oxytocin). CONCLUSIONS: Implementation of the BetterBirth Program, incorporating supply availability, resulted in modest improvements with catch-up by control facilities by 12 months. Supply-chain coaching may be most beneficial in sites starting with lower supply availability. Efforts are needed to reduce reliance on patient-funding for some critical medications. TRIAL REGISTRATION: ClinicalTrials.gov #NCT02148952; Universal Trial Number: U1111-1131-5647.

Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures.

BACKGROUND: Mother-to-child transmission of human immunodeficiency virus-type 1 (HIV-1) poses a serious health threat in developing countries, and adequate interventions are as yet unrealized. HIV-1 infection is frequently initiated by a single founder viral variant, but the factors that influence particular variant selection are poorly understood. RESULTS: Our analysis of 647 full-length HIV-1 subtype C and G viral envelope sequences from 22 mother-infant pairs reveals unique genotypic and phenotypic signatures that depend upon transmission route. Relative to maternal strains, intrauterine HIV transmission selects infant variants that have shorter, less-glycosylated V1 loops that are more resistant to soluble CD4 (sCD4) neutralization. Transmission through breastfeeding selects for variants with fewer potential glycosylation sites in gp41, are more sensitive to the broadly neutralizing antibodies PG9 and PG16, and that bind sCD4 with reduced cooperativity. Furthermore, experiments with Affinofile cells indicate that infant viruses, regardless of transmission route, require increased levels of surface CD4 receptor for productive infection. CONCLUSIONS: These data provide the first evidence for transmission route-specific selection of HIV-1 variants, potentially informing therapeutic strategies and vaccine designs that can be tailored to specific modes of vertical HIV transmission.

The influence of quality maternity waiting homes on utilization of facilities for delivery in rural Zambia.

BACKGROUND: Residential accommodation for expectant mothers adjacent to health facilities, known as maternity waiting homes (MWH), is an intervention designed to improve access to skilled deliveries in low-income countries like Zambia where the maternal mortality ratio is estimated at 398 deaths per 100,000 live births. Our study aimed to assess the relationship between MWH quality and the likelihood of facility delivery in Kalomo and Choma Districts in Southern Province, Zambia. METHODS: We systematically assessed and inventoried the functional capacity of all existing MWH using a quantitative facility survey and photographs of the structures. We calculated a composite score and used multivariate regression to quantify MWH quality and its association with the likelihood of facility delivery using household survey data collected on delivery location in Kalomo and Choma Districts from 2011-2013. RESULTS: MWH were generally in poor condition and composite scores varied widely, with a median score of 28.0 and ranging from 12 to 66 out of a possible 75 points. Of the 17,200 total deliveries captured from 2011-2013 in 40 study catchment area facilities, a higher proportion occurred in facilities where there was either a MWH or the health facility provided space for pregnant waiting mothers compared to those with no accommodations (60.7% versus 55.9%, p <0.001). After controlling for confounders including implementation of Saving Mothers Giving Life, a large-scale maternal health systems strengthening program, among women whose catchment area facilities had an MWH, those women with MWHs in their catchment area that were rated medium or high quality had a 95% increase in the odds of facility delivery than those whose catchment area MWHs were of poor quality (OR: 1.95, 95% CI 1.76, 2.16). CONCLUSIONS: Improving both the availability and the quality of MWH represents a potentially useful strategy to increasing facility delivery in rural Zambia. TRIAL REGISTRATION: The Zambia Chlorhexidine Application Trial is registered at Clinical Trials.gov (identifier: NCT01241318).

Avoidable maternal and neonatal deaths associated with improving access to caesarean delivery in countries with low caesarean delivery rates: an ecological modelling analysis.

BACKGROUND: Reducing maternal and neonatal deaths are important global health priorities. We have previously shown that up to a country-level caesarean delivery rate (CDRs) of roughly 19·0%, cesarean delivery rates and maternal mortality ratio (MMR) and neonatal mortality rate (NMR) were inversely correlated. We investigated the absolute reductions in maternal and neonatal deaths if countries with low CDR increased their rates to a range of greater than 7·2% but less than or equal to 19·1%. METHODS: We calculated maternal and neonatal deaths in 2013 and 2012, respectively, for countries with CDR 7·2% or less (N=45) with available data from the World Bank Development Indicators. We modelled the expected reduction in deaths in these countries if they had the 25th and 75th MMR and NMR percentiles observed for countries (N=48) with CDRs ranging from greater than 7·2% but less than or equal to 19·1%. This model assumes that if countries with low CDRs increased their rates of caesarean delivery to greater than 7·2% but less than or equal to 19·1%, they would achieve levels of MMR and NMR observed in countries with those CDRs. FINDINGS: We estimate 176 078 (95% CI 163 258-188 898) maternal and 1 117 257 (95% CI 1 033 611-1 200 902) neonatal deaths occurred in 45 countries with low CDRs in 2013 and 2012, respectively. If these countries had the 25th and 75th MMR and NMR percentiles (MMR, IQR 36-190; NMR, 9-24) observed in countries (N=48) with a CDR ranging from greater than 7·2% but less than or equal to 19·1%, there would be a potential reduction of 109 762-163 513 and 279 584-803 129 maternal and neonatal deaths, respectively. INTERPRETATION: Increasing caesarean delivery in countries with low CDRs could avert as many as 163 513 maternal deaths and 803 129 neonatal deaths annually. These findings assume that as health systems develop the capacity to deliver surgical care, there is a concurrent improvement in the quality of care and in the ability to rescue women and neonates who would otherwise die. Improving access to safe caesarean delivery should be a central focus in surgical care globally. FUNDING: None.

Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries.

OBJECTIVE: To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries. METHODS: We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality. FINDINGS: Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality. CONCLUSION: Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings.

Demand-side interventions for maternal care: evidence of more use, not better outcomes.

BACKGROUND: Reducing maternal and neonatal mortality is essential to improving population health. Demand-side interventions are designed to increase uptake of critical maternal health services, but associated change in service uptake and outcomes is varied. We undertook a literature review to understand current evidence of demand-side intervention impact on improving utilization and outcomes for mothers and newborn children. METHODS: We completed a rapid review of literature in PubMed. Title and abstracts of publications identified from selected search terms were reviewed to identify articles meeting inclusion criteria: demand-side intervention in low or middle-income countries (LMIC), published after September 2004 and before March 2014, study design describing and reporting on >1 priority outcome: utilization (antenatal care visits, facility-based delivery, delivery with a skilled birth attendant) or health outcome measures (maternal mortality ratio (MMR), stillbirth rate, perinatal mortality rate (PMR), neonatal mortality rate (NMR)). Bibliographies were searched to identify additional relevant papers. Articles were abstracted using a standardized data collection template with double extraction on a sample to ensure quality. Quality of included studies was assessed using McMaster University's Quality Assessment Tool from the Effective Public Health Practice Project (EPHPP). RESULTS: Five hundred and eighty two articles were screened with 50 selected for full review and 16 meeting extraction criteria (eight community mobilization interventions (CM), seven financial incentive interventions (FI), and one with both). We found that demand-side interventions were effective in increasing uptake of key services with five CM and all seven FI interventions reporting increased use of maternal health services. Association with health outcome measures were varied with two studies reporting reductions in MMR and four reporting reduced NMR. No studies found a reduction in stillbirth rate. Only four of the ten studies reporting on both utilization and outcomes reported improvement in both measures. CONCLUSIONS: We found strong evidence that demand-side interventions are associated with increased utilization of services with more variable evidence of their impact on reducing early neonatal and maternal mortality. Further research is needed to understand how to maximize the potential of demand-side interventions to improve maternal and neonatal health outcomes including the role of quality improvement and coordination with supply-side interventions.