Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation.

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. METHODS: We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. FINDINGS: Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. INTERPRETATION: KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. FUNDING: Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

National, regional, and global estimates of low birthweight in 2020, with trends from 2000: a systematic analysis.

BACKGROUND: Low birthweight (LBW; <2500 g) is an important predictor of health outcomes throughout the life course. We aimed to update country, regional, and global estimates of LBW prevalence for 2020, with trends from 2000, to assess progress towards global targets to reduce LBW by 30% by 2030. METHODS: For this systematic analysis, we searched population-based, nationally representative data on LBW from Jan 1, 2000, to Dec 31, 2020. Using 2042 administrative and survey datapoints from 158 countries and areas, we developed a Bayesian hierarchical regression model incorporating country-specific intercepts, time-varying covariates, non-linear time trends, and bias adjustments based on data quality. We also provided novel estimates by birthweight subgroups. FINDINGS: An estimated 19·8 million (95% credible interval 18·4-21·7 million) or 14·7% (13·7-16·1) of liveborn newborns were LBW worldwide in 2020, compared with 22·1 million (20·7-23·9 million) and 16·6% (15·5-17·9) in 2000-an absolute reduction of 1·9 percentage points between 2000 and 2020. Using 2012 as the baseline, as this is when the Global Nutrition Target began, the estimated average annual rate of reduction from 2012 to 2020 was 0·3% worldwide, 0·85% in southern Asia, and 0·59% in sub-Saharan Africa. Nearly three-quarters of LBW births in 2020 occurred in these two regions: of 19 833 900 estimated LBW births worldwide, 8 817 000 (44·5%) were in southern Asia and 5 381 300 (27·1%) were in sub-Saharan Africa. Of 945 300 estimated LBW births in northern America, Australia and New Zealand, central Asia, and Europe, approximately 35·0% (323 700) weighed less than 2000 g: 5·8% (95% CI 5·2-6·4; 54 800 [95% CI 49 400-60 800]) weighed less than 1000 g, 9·0% (8·7-9·4; 85 400 [82 000-88 900]) weighed between 1000 g and 1499 g, and 19·4% (19·0-19·8; 183 500 [180 000-187 000]) weighed between 1500 g and 1999 g. INTERPRETATION: Insufficient progress has occurred over the past two decades to meet the Global Nutrition Target of a 30% reduction in LBW between 2012 and 2030. Accelerating progress requires investments throughout the lifecycle focused on primary prevention, especially for adolescent girls and women living in the most affected countries. With increasing numbers of births in facilities and advancing electronic information systems, improvements in the quality and availability of administrative LBW data are also achievable. FUNDING: The Children's Investment Fund Foundation; the UNDP-UNFPA-UNICEF-WHO World Bank Special Programme of Research, Development and Research Training in Human Reproduction; and the Bill & Melinda Gates Foundation.

Quantifying health facility service readiness for small and sick newborn care: comparing standards-based and WHO level-2 + scoring for 64 hospitals implementing with NEST360 in Kenya, Malawi, Nigeria, and Tanzania.

BACKGROUND: Service readiness tools are important for assessing hospital capacity to provide quality small and sick newborn care (SSNC). Lack of summary scoring approaches for SSNC service readiness means we are unable to track national targets such as the Every Newborn Action Plan targets. METHODS: A health facility assessment (HFA) tool was co-designed by Newborn Essential Solutions and Technologies (NEST360) and UNICEF with four African governments. Data were collected in 68 NEST360-implementing neonatal units in Kenya, Malawi, Nigeria, and Tanzania (September 2019-March 2021). Two summary scoring approaches were developed: a) standards-based, including items for SSNC service readiness by health system building block (HSBB), and scored on availability and functionality, and b) level-2 + , scoring items on readiness to provide WHO level-2 + clinical interventions. For each scoring approach, scores were aggregated and summarised as a percentage and equally weighted to obtain an overall score by hospital, HSBB, and clinical intervention. RESULTS: Of 1508 HFA items, 1043 (69%) were included in standards-based and 309 (20%) in level-2 + scoring. Sixty-eight neonatal units across four countries had median standards-based scores of 51% [IQR 48-57%] at baseline, with variation by country: 62% [IQR 59-66%] in Kenya, 49% [IQR 46-51%] in Malawi, 50% [IQR 42-58%] in Nigeria, and 55% [IQR 53-62%] in Tanzania. The lowest scoring was family-centred care [27%, IQR 18-40%] with governance highest scoring [76%, IQR 71-82%]. For level-2 + scores, the overall median score was 41% [IQR 35-51%] with variation by country: 50% [IQR 44-53%] in Kenya, 41% [IQR 35-50%] in Malawi, 33% [IQR 27-37%] in Nigeria, and 41% [IQR 32-52%] in Tanzania. Readiness to provide antibiotics by culture report was the highest-scoring intervention [58%, IQR 50-75%] and neonatal encephalopathy management was the lowest-scoring [21%, IQR 8-42%]. In both methods, overall scores were low (< 50%) for 27 neonatal units in standards-based scoring and 48 neonatal units in level-2 + scoring. No neonatal unit achieved high scores of > 75%. DISCUSSION: Two scoring approaches reveal gaps in SSNC readiness with no neonatal units achieving high scores (> 75%). Government-led quality improvement teams can use these summary scores to identify areas for health systems change. Future analyses could determine which items are most directly linked with quality SSNC and newborn outcomes.

Health facility assessment of small and sick newborn care in low- and middle-income countries: systematic tool development and operationalisation with NEST360 and UNICEF.

BACKGROUND: Each year an estimated 2.3 million newborns die in the first 28 days of life. Most of these deaths are preventable, and high-quality neonatal care is fundamental for surviving and thriving. Service readiness is used to assess the capacity of hospitals to provide care, but current health facility assessment (HFA) tools do not fully evaluate inpatient small and sick newborn care (SSNC). METHODS: Health systems ingredients for SSNC were identified from international guidelines, notably World Health Organization (WHO), and other standards for SSNC. Existing global and national service readiness tools were identified and mapped against this ingredients list. A novel HFA tool was co-designed according to a priori considerations determined by policymakers from four African governments, including that the HFA be completed in one day and assess readiness across the health system. The tool was reviewed by > 150 global experts, and refined and operationalised in 64 hospitals in Kenya, Malawi, Nigeria, and Tanzania between September 2019 and March 2021. RESULTS: Eight hundred and sixty-six key health systems ingredients for service readiness for inpatient SSNC were identified and mapped against four global and eight national tools measuring SSNC service readiness. Tools revealed major content gaps particularly for devices and consumables, care guidelines, and facility infrastructure, with a mean of 13.2% (n = 866, range 2.2-34.4%) of ingredients included. Two tools covered 32.7% and 34.4% (n = 866) of ingredients and were used as inputs for the new HFA tool, which included ten modules organised by adapted WHO health system building blocks, including: infrastructure, pharmacy and laboratory, medical devices and supplies, biomedical technician workshop, human resources, information systems, leadership and governance, family-centred care, and infection prevention and control. This HFA tool can be conducted at a hospital by seven assessors in one day and has been used in 64 hospitals in Kenya, Malawi, Nigeria, and Tanzania. CONCLUSION: This HFA tool is available open-access to adapt for use to comprehensively measure service readiness for level-2 SSNC, including respiratory support. The resulting facility-level data enable comparable tracking for Every Newborn Action Plan coverage target four within and between countries, identifying facility and national-level health systems gaps for action.

Closing the birth registration gap for Every newborn facility birth: literature review and qualitative research.

BACKGROUND: Birth registration is vital to provide legal identity and access to essential services. Worldwide, approximately 166 million children under five years (just under 25%) are unregistered, yet >80% of all births occur in health facilities in most low- and middle-income countries (LMIC). OBJECTIVES: This study, conducted in association with UNICEF, aims to review facility-based birth registration initiatives, and provide recommendations to close the gap between facility birth and birth registration rates in LMIC. METHODS: A literature review covering published and grey literature was conducted to identify facility-based initiatives to increase birth registration rates. Semi-structured in-depth interviews were conducted by audio-call with six key global stakeholders to identify additional initiatives, and further insights for barriers and enablers to close the gap. RESULTS: Academic databases and grey literature search yielded 21 studies meeting pre-specified inclusion criteria. Nine barriers preventing birth registration were identified and grouped into three themes: health system, governmental, and societal barriers. Facility-based birth registration initiatives resulted in an increase in birth registration rates. Importantly, health promotion within communities also increased demand for birth registration. In-depth interview respondents provided further detail and supported data found in literature review. Synthesis of the literature and stakeholder interviews noted enablers including inter-sectoral collaboration between health sector and civil registration ministries e.g., placing civil registration offices in health facilities or allowing medical doctors to act as registrars. CONCLUSION: Facility-based birth registration initiatives can increase birth registration rates in LMIC. Initiatives need to address both supply and demand side of birth registration to improve facility-based birth registration rates. A multi-sectoral approach within governments, and alignment with multiple stakeholders is vital.

Investment case for small and sick newborn care in Tanzania: systematic analyses.

BACKGROUND: Small and sick newborn care (SSNC) is critical for national neonatal mortality reduction targets by 2030. Investment cases could inform implementation planning and enable coordinated resource mobilisation. We outline development of an investment case for Tanzania to estimate additional financing for scaling up SSNC to 80% of districts as part of health sector strategies to meet the country's targets. METHODS: We followed five steps: (1) reviewed national targets, policies and guidelines; (2) modelled potential health benefits by increased coverage of SSNC using the Lives Saved Tool; (3) estimated setup and running costs using the Neonatal Device Planning and Costing Tool, applying two scenarios: (A) all new neonatal units and devices with optimal staffing, and (B) half new and half modifying, upgrading, or adding resources to existing neonatal units; (4) calculated budget impact and return on investment (ROI) and (5) identified potential financing opportunities. RESULTS: Neonatal mortality rate was forecast to fall from 20 to 13 per 1000 live births with scale-up of SSNC, superseding the government 2025 target of 15, and close to the 2030 Sustainable Development Goal 3.2 target of <12. At 85% endline coverage, estimated cumulative lives saved were 36,600 by 2025 and 80,000 by 2030. Total incremental costs were estimated at US$166 million for scenario A (US$112 million set up and US$54 million for running costs) and US$90 million for scenario B (US$65 million setup and US$25 million for running costs). Setup costs were driven by infrastructure (83%) and running costs by human resources (60%). Cost per capita was US$0.93 and the ROI is estimated to be between US$8-12 for every dollar invested. CONCLUSIONS: ROI for SSNC is higher compared to other health investments, noting many deaths averted followed by full lifespan. This is conservative since disability averted is not included. Budget impact analysis estimated a required 2.3% increase in total government health expenditure per capita from US$40.62 in 2020, which is considered affordable, and the government has already allocated additional funding. Our proposed five-step SSNC investment case has potential for other countries wanting to accelerate progress.

Protecting small and sick newborn care in the COVID-19 pandemic: multi-stakeholder qualitative data from four African countries with NEST360.

BACKGROUND: Health system shocks are increasing. The COVID-19 pandemic resulted in global disruptions to health systems, including maternal and newborn healthcare seeking and provision. Yet evidence on mitigation strategies to protect newborn service delivery is limited. We sought to understand what mitigation strategies were employed to protect small and sick newborn care (SSNC) across 65 facilities Kenya, Malawi, Nigeria and Tanzania, implementing with the NEST360 Alliance, and if any could be maintained post-pandemic. METHODS: We used qualitative methods (in-depth interviews n=132, focus group discussions n=15) with purposively sampled neonatal health systems actors in Kenya, Malawi, Nigeria and Tanzania. Data were collected from September 2021 - August 2022. Topic guides were co-developed with key stakeholders and used to gain a detailed understanding of approaches to protect SSNC during the COVID-19 pandemic. Questions explored policy development, collaboration and investments, organisation of care, human resources, and technology and device innovations. Interviews were conducted by experienced qualitative researchers and data were collected until saturation was reached. Interviews were digitally recorded and transcribed verbatim. A common coding framework was developed, and data were coded via NVivo and analysed using a thematic framework approach. FINDINGS: We identified two pathways via which SSNC was strengthened. The first pathway, COVID-19 specific responses with secondary benefit to SSNC included: rapid policy development and adaptation, new and collaborative funding partnerships, improved oxygen systems, strengthened infection prevention and control practices. The second pathway, health system mitigation strategies during the pandemic, included: enhanced information systems, human resource adaptations, service delivery innovations, e.g., telemedicine, community engagement and more emphasis on planned preventive maintenance of devices. Chronic system weaknesses were also identified that limited the sustainability and institutionalisation of actions to protect SSNC. CONCLUSION: Innovations to protect SSNC in response to the COVID-19 pandemic should be maintained to support resilience and high-quality routine SSNC delivery. In particular, allocation of resources to sustain high quality and resilient care practices and address remaining gaps for SSNC is critical.

Stillbirths: Contribution of preterm birth and size-for-gestational age for 125.4 million total births from nationwide records in 13 countries, 2000-2020.

OBJECTIVE: To examine the contribution of preterm birth and size-for-gestational age in stillbirths using six 'newborn types'. DESIGN: Population-based multi-country analyses. SETTING: Births collected through routine data systems in 13 countries. SAMPLE: 125 419 255 total births from 22+0 to 44+6 weeks' gestation identified from 2000 to 2020. METHODS: We included 635 107 stillbirths from 22+0 weeks' gestation from 13 countries. We classified all births, including stillbirths, into six 'newborn types' based on gestational age information (preterm, PT, <37+0 weeks versus term, T, ≥37+0 weeks) and size-for-gestational age defined as small (SGA, <10th centile), appropriate (AGA, 10th-90th centiles) or large (LGA, >90th centile) for gestational age, according to the international newborn size for gestational age and sex INTERGROWTH-21st standards. MAIN OUTCOME MEASURES: Distribution of stillbirths, stillbirth rates and rate ratios according to six newborn types. RESULTS: 635 107 (0.5%) of the 125 419 255 total births resulted in stillbirth after 22+0 weeks. Most stillbirths (74.3%) were preterm. Around 21.2% were SGA types (PT + SGA [16.2%], PT + AGA [48.3%], T + SGA [5.0%]) and 14.1% were LGA types (PT + LGA [9.9%], T + LGA [4.2%]). The median rate ratio (RR) for stillbirth was highest in PT + SGA babies (RR 81.1, interquartile range [IQR], 68.8-118.8) followed by PT + AGA (RR 25.0, IQR, 20.0-34.3), PT + LGA (RR 25.9, IQR, 13.8-28.7) and T + SGA (RR 5.6, IQR, 5.1-6.0) compared with T + AGA. Stillbirth rate ratios were similar for T + LGA versus T + AGA (RR 0.7, IQR, 0.7-1.1). At the population level, 25% of stillbirths were attributable to small-for-gestational-age. CONCLUSIONS: In these high-quality data from high/middle income countries, almost three-quarters of stillbirths were born preterm and a fifth small-for-gestational age, with the highest stillbirth rates associated with the coexistence of preterm and SGA. Further analyses are needed to better understand patterns of gestation-specific risk in these populations, as well as patterns in lower-income contexts, especially those with higher rates of intrapartum stillbirth and SGA.

Neonatal mortality risk of large-for-gestational-age and macrosomic live births in 15 countries, including 115.6 million nationwide linked records, 2000-2020.

OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

Neonatal inpatient dataset for small and sick newborn care in low- and middle-income countries: systematic development and multi-country operationalisation with NEST360.

BACKGROUND: Every Newborn Action Plan (ENAP) coverage target 4 necessitates national scale-up of Level-2 Small and Sick Newborn Care (SSNC) (with Continuous Positive Airway Pressure (CPAP)) in 80% of districts by 2025. Routine neonatal inpatient data is important for improving quality of care, targeting equity gaps, and enabling data-driven decision-making at individual, district, and national-levels. Existing neonatal inpatient datasets vary in purpose, size, definitions, and collection processes. We describe the co-design and operationalisation of a core inpatient dataset for use to track outcomes and improve quality of care for small and sick newborns in high-mortality settings. METHODS: A three-step systematic framework was used to review, co-design, and operationalise this novel neonatal inpatient dataset in four countries (Malawi, Kenya, Tanzania, and Nigeria) implementing with the Newborn Essential Solutions and Technologies (NEST360) Alliance. Existing global and national datasets were identified, and variables were mapped according to categories. A priori considerations for variable inclusion were determined by clinicians and policymakers from the four African governments by facilitated group discussions. These included prioritising clinical care and newborn outcomes data, a parsimonious variable list, and electronic data entry. The tool was designed and refined by > 40 implementers and policymakers during a multi-stakeholder workshop and online interactions. RESULTS: Identified national and international datasets (n = 6) contained a median of 89 (IQR:61-154) variables, with many relating to research-specific initiatives. Maternal antenatal/intrapartum history was the largest variable category (21, 23.3%). The Neonatal Inpatient Dataset (NID) includes 60 core variables organised in six categories: (1) birth details/maternal history; (2) admission details/identifiers; (3) clinical complications/observations; (4) interventions/investigations; (5) discharge outcomes; and (6) diagnosis/cause-of-death. Categories were informed through the mapping process. The NID has been implemented at 69 neonatal units in four African countries and links to a facility-level quality improvement (QI) dashboard used in real-time by facility staff. CONCLUSION: The NEST360 NID is a novel, parsimonious tool for use in routine information systems to inform inpatient SSNC quality. Available on the NEST360/United Nations Children's Fund (UNICEF) Implementation Toolkit for SSNC, this adaptable tool enables facility and country-level comparisons to accelerate progress toward ENAP targets. Additional linked modules could include neonatal at-risk follow-up, retinopathy of prematurity, and Level-3 intensive care.

Blood culture versus antibiotic use for neonatal inpatients in 61 hospitals implementing with the NEST360 Alliance in Kenya, Malawi, Nigeria, and Tanzania: a cross-sectional study.

BACKGROUND: Thirty million small and sick newborns worldwide require inpatient care each year. Many receive antibiotics for clinically diagnosed infections without blood cultures, the current 'gold standard' for neonatal infection detection. Low neonatal blood culture use hampers appropriate antibiotic use, fuelling antimicrobial resistance (AMR) which threatens newborn survival. This study analysed the gap between blood culture use and antibiotic prescribing in hospitals implementing with Newborn Essential Solutions and Technologies (NEST360) in Kenya, Malawi, Nigeria, and Tanzania. METHODS: Inpatient data from every newborn admission record (July 2019-August 2022) were included to describe hospital-level blood culture use and antibiotic prescription. Health Facility Assessment data informed performance categorisation of hospitals into four tiers: (Tier 1) no laboratory, (Tier 2) laboratory but no microbiology, (Tier 3) neonatal blood culture use < 50% of newborns receiving antibiotics, and (Tier 4) neonatal blood culture use > 50%. RESULTS: A total of 144,146 newborn records from 61 hospitals were analysed. Mean hospital antibiotic prescription was 70% (range = 25-100%), with 6% mean blood culture use (range = 0-56%). Of the 10,575 blood cultures performed, only 24% (95%CI 23-25) had results, with 10% (10-11) positivity. Overall, 40% (24/61) of hospitals performed no blood cultures for newborns. No hospitals were categorised as Tier 1 because all had laboratories. Of Tier 2 hospitals, 87% (20/23) were District hospitals. Most hospitals could do blood cultures (38/61), yet the majority were categorised as Tier 3 (36/61). Only two hospitals performed > 50% blood cultures for newborns on antibiotics (Tier 4). CONCLUSIONS: The two Tier 4 hospitals, with higher use of blood cultures for newborns, underline potential for higher blood culture coverage in other similar hospitals. Understanding why these hospitals are positive outliers requires more research into local barriers and enablers to performing blood cultures. Tier 3 facilities are missing opportunities for infection detection, and quality improvement strategies in neonatal units could increase coverage rapidly. Tier 2 facilities could close coverage gaps, but further laboratory strengthening is required. Closing this culture gap is doable and a priority for advancing locally-driven antibiotic stewardship programmes, preventing AMR, and reducing infection-related newborn deaths.

Devices and furniture for small and sick newborn care: systematic development of a planning and costing tool.

BACKGROUND: High-quality neonatal care requires sufficient functional medical devices, furniture, fixtures, and use by trained healthcare workers, however there is lack of publicly available tools for quantification and costing. This paper describes development and use of a planning and costing tool regarding furniture, fixtures and devices to support scale-up of WHO level-2 neonatal care, for national and global newborn survival targets. METHODS: We followed a systematic process. First, we reviewed planning and costing tools of relevance. Second, we co-designed a new tool to estimate furniture and device set-up costs for a default 40-bed level-2 neonatal unit, incorporating input from multi-disciplinary experts and newborn care guidelines. Furniture and device lists were based off WHO guidelines/norms, UNICEF and national manuals/guides. Due to lack of evidence-based quantification, ratios were based on operational manuals, multi-country facility assessment data, and expert opinion. Default unit costs were from government procurement agency costs in Kenya, Nigeria, and Tanzania. Third, we refined the tool by national use in Tanzania. RESULTS: The tool adapts activity-based costing (ABC) to estimate quantities and costs to equip a level-2 neonatal unit based on three components: (1) furniture/fixtures (18 default but editable items); (2) neonatal medical devices (16 product categories with minimum specifications for use in low-resource settings); (3) user training at device installation. The tool was used in Tanzania to generate procurement lists and cost estimates for level-2 scale-up in 171 hospitals (146 District and 25 Regional Referral). Total incremental cost of all new furniture and equipment acquisition, installation, and user training were US$93,000 per District hospital (level-2 care) and US$346,000 per Regional Referral hospital. Estimated cost per capita for whole-country district coverage was US$0.23, representing 0.57% increase in government health expenditure per capita and additional 0.35% for all Regional Referral hospitals. CONCLUSION: Given 2.3 million neonatal deaths and potential impact of level-2 newborn care, rational and efficient planning of devices linked to systems change is foundational. In future iterations, we aim to include consumables, spare parts, and maintenance cost options. More rigorous implementation research data are crucial to formulating evidence-based ratios for devices numbers per baby. Use of this tool could help overcome gaps in devices numbers, advance efficiency and quality of neonatal care.

National routine data for low birthweight and preterm births: Systematic data quality assessment for United Nations member states (2000-2020).

OBJECTIVE: Low birthweight (<2500 g) and preterm birth (<37 weeks) are markers of newborn vulnerability. To facilitate informed decisions about investments in prevention and care, it is imperative to enhance data quality and use. Hence, the objective of this study is to systematically assess the quality of data concerning low birthweight and preterm births within routine administrative data sources. DESIGN: Systematic data quality assessment by adopting the WHO Data Quality Framework. SETTING: National routine data system from UN member states. POPULATION: Livebirths. METHODS: National routine administrative data on low birthweight and preterm births for 195 countries from 2000 to 2020 were systematically collated, totalling >700 million live births. The WHO data quality framework was adapted to undertake standardised data quality assessments. MAIN OUTCOME MEASURES: Availability, reporting quality, internal and external consistency of low birthweight and preterm data. RESULTS: Most United States Member States (64%: 124/195) had national data on low birthweight and (40%: 82/195) had data on preterm birth. Routine data system reporting was highest in North America, Australasia and Europe, where more than 95% live births had data on low birthweight and over 75% had data preterm births. In contrast, data reporting was lowest in sub-Saharan Africa (13% for low birthweight, 8% for preterm births) and Southern Asia (16% for low birthweight, 5% for preterm births). Most countries collect individual-level data; but, aggregate data reporting from hospital-based systems remain common in sub-Saharan Africa and Southern Asia. While data quality was generally high in North America, Australasia and Europe, gaps remain in the availability of gestational age metadata. Consistency between low birthweight and preterm rates were poor in Southern Asia and sub-Saharan Africa regions across time. There was high external consistency between low birthweight rates obtained from routine administrative data compared with low birthweight rates obtained from survey data for countries with high data quality. CONCLUSIONS: Sub-Saharan Africa and South Asia countries have data gaps but also opportunities for rapid progress. Most births occure in facilities, electronic health information systems already include low birthweight, and adding accurate gestational age including with ultrasound assessment is becoming increasingly attainable. Moving toward the collection of individual level data would enable monitoring of quality of care and longer-term outcomes. This is crucial for every child and family and essential for measuring progress towards relevant sustainable development goals. The assessment will inform countries' actions for data quality improvement at national level and use of data for impact.

National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects. This study updated national preterm birth rates and trends, plus novel estimates by gestational age subgroups, to inform progress towards global health goals and targets, and aimed to update country, regional, and global estimates of preterm birth for 2020 in addition to trends between 2010 and 2020. METHODS: We systematically searched population-based, nationally representative data on preterm birth from Jan 1, 2010, to Dec 31, 2020 and study data (26 March-14 April, 2021) for countries and areas with no national-level data. The analysis included 679 data points (86% nationally representative administrative data [582 of 679 data points]) from 103 countries and areas (62% of countries and areas having nationally representative administrative data [64 of 103 data points]). A Bayesian hierarchical regression was used for estimating country-level preterm rates, which incoporated country-specific intercepts, low birthweight as a covariate, non-linear time trends, and bias adjustments based on a data quality categorisation, and other indicators such as method of gestational age estimation. FINDINGS: An estimated 13·4 million (95% credible interval [CrI] 12·3-15·2 million) newborn babies were born preterm (<37 weeks) in 2020 (9·9% of all births [95% CrI 9·1-11·2]) compared with 13·8 million (12·7-15·5 million) in 2010 (9·8% of all births [9·0-11·0]) worldwide. The global annual rate of reduction was estimated at -0·14% from 2010 to 2020. In total, 55·6% of total livebirths are in southern Asia (26·8% [36 099 000 of 134 767 000]) and sub-Saharan Africa (28·7% [38 819 300 of 134 767 000]), yet these two regions accounted for approximately 65% (8 692 000 of 13 376 200) of all preterm births globally in 2020. Of the 33 countries and areas in the highest data quality category, none were in southern Asia or sub-Saharan Africa compared with 94% (30 of 32 countries) in high-income countries and areas. Worldwide from 2010 to 2020, approximately 15% of all preterm births occurred at less than 32 weeks of gestation, requiring more neonatal care (<28 weeks: 4·2%, 95% CI 3·1-5·0, 567 800 [410 200-663 200 newborn babies]); 28-32 weeks: 10·4% [9·5-10·6], 1 392 500 [1 274 800-1 422 600 newborn babies]). INTERPRETATION: There has been no measurable change in preterm birth rates over the last decade at global level. Despite increasing facility birth rates and substantial focus on routine health data systems, there remain many missed opportunities to improve preterm birth data. Gaps in national routine data for preterm birth are most marked in regions of southern Asia and sub-Saharan Africa, which also have the highest estimated burden of preterm births. Countries need to prioritise programmatic investments to prevent preterm birth and to ensure evidence-based quality care when preterm birth occurs. Investments in improving data quality are crucial so that preterm birth data can be improved and used for action and accountability processes. FUNDING: The Children's Investment Fund Foundation and the UNDP, United Nations Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Donor aid mentioning newborns and stillbirths, 2002-19: an analysis of levels, trends, and equity.

BACKGROUND: Global aid for reproductive, maternal, newborn, and child health has stagnated in recent years, and aid mentioning newborns or stillbirths has previously represented a very small proportion of aid for reproductive, maternal, newborn, and child health. Neonatal survival targets have been set by 78 countries, and stillbirth prevention targets have been set by 30 countries, to address the 4·4 million newborn deaths and stillbirths globally. We aimed to generate novel estimates of current levels of, and trends in, aid mentioning newborns and stillbirths over 2002-19, and to assess whether the amount of aid disbursed aligns with the associated mortality burden. METHODS: For this analysis, we did a manual review and coding of the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System database from 2002 to 2019 using key search terms for aid mentioning newborns and stillbirths. We compared these findings with estimates of aid for reproductive, maternal, newborn, and child health for 2002-19 based on the Muskoka2 method. Findings are presented in 2019 US$ according to the OECD's Development Assistance Committee deflators, which account for variation in exchange rates and inflation in donor countries. FINDINGS: We identified 21 957 unique records in the 2002-19 period. Aid mentioning newborns and stillbirths comprised approximately 10% ($1·6 billion) of reproductive, maternal, newborn, and child health funding overall in 2019 ($15·9 billion), with a small decrease in value between 2015 and 2019. 1284 (6%) of 21 957 records and 3·4% ($535 million) of their total value mentioned aid focused only on newborn health. Ten donors contributed 87% ($13·7 billion) of the total value of aid mentioning newborns and stillbirths during 2002-19. Aid mentioning newborns and stillbirths was inequitably allocated in the least developed countries (as defined by the UN), ranging from $18 per death in Angola to $1389 per death in Timor-Leste. Stillbirths were not mentioned in any funding in 2002-09, and they were only mentioned in 46 of 21 957 records in 2010-19, comprising $44·4 million of aid disbursed during this period. INTERPRETATION: Aid mentioning newborns and stillbirths is poorly matched to their corresponding mortality burden (representing 10% of aid for reproductive, maternal, newborn, and child health overall, yet accounting for approximately 50% of mortality in children <5 years) and across recipient countries (with substantial variation in the amount of aid received per newborn death and stillbirth between countries with similar health and economic needs). Our findings indicate that aid needs to be better targeted to populations with the highest mortality burdens, creating greater potential for impact. FUNDING: John D and Catherine T MacArthur Foundation, Bill & Melinda Gates Foundation, ELMA Philanthropies, Children's Investment Fund Foundation UK, Lemelson Foundation, and Ting Tsung and Wei Fong Chao Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Research funding for newborn health and stillbirths, 2011-20: a systematic analysis of levels and trends.

BACKGROUND: Worldwide, an estimated 4·4 million newborn deaths and stillbirths occurred in 2020, and 98% of these deaths occurred in low-income and middle-income countries (LMICs). We aimed to analyse new research grants for newborns and stillbirth awarded by major funders in 2019-20, and all research funding allocated to LMIC-based institutions in 2011-20. METHODS: For this systematic analysis, we searched Dimensions, the world's largest research funding database, for grants relevant to neonatal and stillbirth research. Included grants were categorised by in-depth content analysis, with descriptive quantitative analyses by funder and recipient countries, research pipeline, topic, and year. FINDINGS: Globally, in 2019-20, major funders awarded a mean annual total of US$577·1 million per year for newborn and stillbirth research (mean total of 550 grants per year). $166·3 million (28·8%) of $577·1 million was directed to small and vulnerable newborn research, but only $8·4 million (1·5%) was directed to stillbirth research. The majority of funding, $537·0 million (93·0%), was allocated to organisations based in high-income countries. Between 2011 and 2020, LMIC-based recipients were named on 1985 grants from all funders worth $486·7 million, of which $73·1 million (15·0%) was allocated to small and vulnerable newborn research and $12·0 million (2·5%) was allocated to stillbirth research. Most LMIC funding supported preclinical or observational studies ($236·8 million [48·7%] of $486·7 million), with implementation research receiving only $13·9 million (2·9%). INTERPRETATION: Although investment in research related to neonatal health and stillbirths has increased between 2011 and 2020, there are marked disparities in distribution geographically, between major causes of mortality, and among research pipeline types. Stillbirth research received minimal funding in both high-income countries and LMICs, despite a similar number of deaths compared with neonates. Direct investment in LMIC-led research, especially for implementation research, could accelerate the slow global progress on stillbirth prevention and newborn survival. FUNDING: None. TRANSLATIONS: For the French, German and Spanish translations of the abstract see Supplementary Materials section.

Inferring longitudinal patterns of group B Streptococcus colonization during pregnancy.

Maternal colonization by Group B Streptococcus (GBS) can lead to severe infection in neonates and has also been associated with prematurity and stillbirth. Better quantitative understanding of the trajectories of GBS carriage during pregnancy is essential for the design of informative epidemiological studies. Here, we describe analyses of published longitudinal data using Bayesian hidden Markov models, which involve the estimation of parameters related to the succession of latent states (infection status) and observations (culture positivity). In addition to quantifying infection acquisition and clearance probabilities, the statistical approach also suggests that for some longitudinal patterns of culture results, pregnant women were likely to have been GBS-colonized despite a negative diagnostic result. We believe this method, if used in future longitudinal studies of maternal GBS colonization, would improve our understanding of the pathologies linked to this bacterium and could also inform maternal GBS vaccine trial design.

Acquisition and carriage of genetically diverse multi-drug resistant gram-negative bacilli in hospitalised newborns in The Gambia.

BACKGROUND: This detailed genomic study characterised multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in neonates < 2 kg and paired mothers at a low-resource African hospital. METHODS: This cross-sectional cohort study was conducted at the neonatal referral unit in The Gambia with weekly neonatal skin and peri-anal sampling and paired maternal recto-vaginal swabs. Prospective bacteriological culture used MacConkey agar with species identification by API20E and API20NE. All GNB isolates underwent whole genome sequencing on Illumina Miseq platform. Multi-Locus Sequence Typing and SNP-distance analysis identified strain type and relatedness. RESULTS: 135 swabs from 34 neonates and 21 paired mothers, yielded 137 GNB isolates, of which 112 are high quality de novo assemblies. Neonatal MDR-GNB carriage prevalence is 41% (14/34) at admission with 85% (11/13) new acquisition by 7d. Multiple MDR and ESBL-GNB species are carried at different timepoints, most frequently K. pneumoniae and E. coli, with heterogeneous strain diversity and no evidence of clonality. 111 distinct antibiotic resistance genes are mostly beta lactamases (Bla-AMPH, Bla-PBP, CTX-M-15, Bla-TEM-105). 76% (16/21) and 62% (13/21) of mothers have recto-vaginal carriage of ≥1 MDR-GNB and ESBL-GNB respectively, mostly MDR-E. coli (76%, 16/21) and MDR-K. pneumoniae (24%, 5/21). Of 21 newborn-mother dyads, only one have genetically identical isolates (E. coli ST131 and K. pneumoniae ST3476). CONCLUSIONS: Gambian hospitalised neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7d with limited evidence supporting mother to neonate transmission. Genomic studies in similar settings are required to further understand transmission and inform targeted surveillance and infection prevention policies.

Bacteria that are resistant to multiple antibiotics are an important cause of infection and death of newborns in low-resource countries, especially small or premature babies born in hospital settings. How these resistant bacteria are acquired on the skin and in the gut of newborns is not known, particularly whether they are commonly transferred from mothers. We studied the bacteria present in small Gambian newborns and their mothers to understand the type of bacteria, amount of antibiotic resistance, number of newborns and mothers affected and similarity of these bacteria between newborns and their mothers. We found that despite many newborns carrying these bacteria, they are different from those present in mothers. This suggests that the bacteria are acquired from the hospital environment. Our study highlights the importance of developing strategies to identify and reduce the presence of such bacteria in hospitals to reduce their acquisition by vulnerable hospitalised newborns.

What more can be done? Prioritizing the most promising antenatal interventions to improve birth weight.

BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.