Cost-effectiveness analysis of heart rate characteristics monitoring to improve survival for very low birth weight infants

Introduction Over 50,000 very low birth weight (VLBW) infants are born each year in the United States. Despite advances in care, these premature babies are subjected to long stays in a neonatal intensive care unit (NICU), and experience high rates of morbidity and mortality. In a large randomized controlled trial (RCT), heart rate characteristics (HRC) monitoring in addition to standard monitoring decreased all-cause mortality among VLBW infants by 22%. We sought to understand the cost-effectiveness of HRC monitoring to improve survival among VLBW infants. Methods We performed a secondary analysis of cost-effectiveness of heart rate characteristics (HRC) monitoring to improve survival from birth to NICU discharge, up to 120 days using data and outcomes from an RCT of 3,003 VLBW patients. We estimated each patient's cost from a third-party perspective in 2021 USD using the resource utilization data gathered during the RCT (NCT00307333) during their initial stay in the NICU and applied to specific per diem rates. We computed the incremental cost-effectiveness ratio and used non-parametric boot-strapping to evaluate uncertainty. Results The incremental cost-effectiveness ratio of HRC-monitoring was $34,720 per life saved. The 95th percentile of cost to save one additional life through HRC-monitoring was$449,291. Conclusion HRC-monitoring appears cost-effective for increasing survival among VLBW infants

Neonatal resuscitation and immediate newborn assessment and stimulation for the prevention of neonatal deaths: a systematic review, meta-analysis and Delphi estimation of mortality effect

BACKGROUND: Of 136 million babies born annually, around 10 million require assistance to breathe. Each year 814,000 neonatal deaths result from intrapartum-related events in term babies (previously "birth asphyxia") and 1.03 million from complications of prematurity. No systematic assessment of mortality reduction from tactile stimulation or resuscitation has been published. OBJECTIVE: To estimate the mortality effect of immediate newborn assessment and stimulation, and basic resuscitation on neonatal deaths due to term intrapartum-related events or preterm birth, for facility and home births. METHODS: We conducted systematic reviews for studies reporting relevant mortality or morbidity outcomes. Evidence was assessed using GRADE criteria adapted to provide a systematic approach to mortality effect estimates for the Lives Saved Tool (LiST). Meta-analysis was performed if appropriate. For interventions with low quality evidence but strong recommendation for implementation, a Delphi panel was convened to estimate effect size. RESULTS: We identified 24 studies of neonatal resuscitation reporting mortality outcomes (20 observational, 2 quasi-experimental, 2 cluster randomized controlled trials), but none of immediate newborn assessment and stimulation alone. A meta-analysis of three facility-based studies examined the effect of resuscitation training on intrapartum-related neonatal deaths (RR= 0.70, 95%CI 0.59-0.84); this estimate was used for the effect of facility-based basic neonatal resuscitation (additional to stimulation). The evidence for preterm mortality effect was low quality and thus expert opinion was sought. In community-based studies, resuscitation training was part of packages with multiple concurrent interventions, and/or studies did not distinguish term intrapartum-related from preterm deaths, hence no meta-analysis was conducted. Our Delphi panel of 18 experts estimated that immediate newborn assessment and stimulation would reduce both intrapartum-related and preterm deaths by 10%, facility-based resuscitation would prevent a further 10% of preterm deaths, and community-based resuscitation would prevent further 20% of intrapartum-related and 5% of preterm deaths. CONCLUSION: Neonatal resuscitation training in facilities reduces term intrapartum-related deaths by 30%. Yet, coverage of this intervention remains low in countries where most neonatal deaths occur and is a missed opportunity to save lives. Expert opinion supports smaller effects of neonatal resuscitation on preterm mortality in facilities and of basic resuscitation and newborn assessment and stimulation at community level. Further evaluation is required for impact, cost and implementation strategies in various contexts. FUNDING: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to the Saving Newborn Lives program of Save the Children, through Save the Children US

Reduced perinatal mortality following enhanced training of birth attendants in the Democratic Republic of Congo: a time-dependent effect

<p>Abstract</p> <p>Background</p> <p>In many developing countries, the majority of births are attended by traditional birth attendants, who lack formal training in neonatal resuscitation and other essential care required by the newly born infant. In these countries, the major causes of neonatal mortality are birth asphyxia, infection, and low-birth-weight/prematurity. Death from these causes is potentially modifiable using low-cost interventions, including neonatal resuscitation training. The purpose of this study was to evaluate the effect on perinatal mortality of training birth attendants in a rural area of the Democratic Republic of Congo (DRC) using two established programs.</p> <p>Methods</p> <p>This study, a secondary analysis of DRC-specific data collected during a multi-country study, was conducted in two phases. The effect of training using the WHO Essential Newborn Care (ENC) program was evaluated using an active baseline design, followed by a cluster randomized trial of training using an adaptation of a neonatal resuscitation program (NRP). The perinatal mortality rates before ENC, after ENC training, and after randomization to additional NRP training or continued care were compared. In addition, the influence of time following resuscitation training was investigated by examining change in perinatal mortality during sequential three-month increments following ENC training.</p> <p>Results</p> <p>More than two-thirds of deliveries were attended by traditional birth attendants and occurred in homes; these proportions decreased after ENC training. There was no apparent decline in perinatal mortality when the outcome of all deliveries prior to ENC training was compared to those after ENC but before NRP training. However, there was a gradual but significant decline in perinatal mortality during the year following ENC training (RR 0.73; 95% CI: 0.56-0.96), which was independently associated with time following training. The decline was attributable to a decline in early neonatal mortality. NRP training had no demonstrable effect on early neonatal mortality.</p> <p>Conclusion</p> <p>Training DRC birth attendants using the ENC program reduces perinatal mortality. However, a period of utilization and re-enforcement of training may be necessary before a decline in mortality occurs. ENC training has the potential to be a low cost, high impact intervention in developing countries.</p> <p>Trial registration</p> <p>This trial has been registered at <url>http://www.clinicaltrials.gov</url> (identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT00136708">NCT00136708</a>).</p

Advancing research on emergency care systems in low-income and middle-income countries: ensuring high-quality care delivery systems

Emergency care systems (ECS) address a wide range of acute conditions, including emergent conditions from communicable diseases, non-communicable diseases, pregnancy and injury. Together, ECS represent an area of great potential for reducing morbidity and mortality in low-income and middle-income countries (LMICs). It is estimated that up to 54% of annual deaths in LMICs could be addressed by improved prehospital and facility-based emergency care. Research is needed to identify strategies for enhancing ECS to optimise prevention and treatment of conditions presenting in this context, yet significant gaps persist in defining critical research questions for ECS studies in LMICs. The Collaborative on Enhancing Emergency Care Research in LMICs seeks to promote research that improves immediate and long-term outcomes for clients and populations with emergent conditions. The objective of this paper is to describe systems approaches and research strategies for ECS in LMICs, elucidate priority research questions and methodology, and present a selection of studies addressing the operational, implementation, policy and health systems domains of health systems research as an approach to studying ECS. Finally, we briefly discuss limitations and the next steps in developing ECS-oriented interventions and research

The Airway Microbiome at Birth.

Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease

Implementation and evaluation of the Helping Babies Breathe curriculum in three resource limited settings: does Helping Babies Breathe save lives? A study protocol

Background: Neonatal deaths account for over 40% of all under-5 year deaths; their reduction is increasingly critical for achieving Millennium Development Goal 4. An estimated 3 million newborns die annually during their first month of life; half of these deaths occur during delivery or within 24 hours. Every year, 6 million babies require help to breathe immediately after birth. Resuscitation training to help babies breathe and prevent/manage birth asphyxia is not routine in low-middle income facility settings. Helping Babies Breathe (HBB), a simulation-training program for babies wherever they are born, was developed for use in low-middle income countries. We evaluated whether HBB training of facility birth attendants reduces perinatal mortality in the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Global Network research sites. Methods/design: We hypothesize that a two-year prospective pre-post study to evaluate the impact of a facility-based training package, including HBB and essential newborn care, will reduce all perinatal mortality (fresh stillbirth or neonatal death prior to 7 days) among the Global Network’s Maternal Neonatal Health Registry births ≥1500 grams in the study clusters served by the facilities. We will also evaluate the effectiveness of the HBB training program changing on facility-based perinatal mortality and resuscitation practices. Seventy-one health facilities serving 52 geographically-defined study clusters in Belgaum and Nagpur, India, and Eldoret, Kenya, and 30,000 women will be included. Primary outcome data will be collected by staff not involved in the HBB intervention. Additional data on resuscitations, resuscitation debriefings, death audits, quality monitoring and improvement will be collected. HBB training will include training of MTs, facility level birth attendants, and quality monitoring and improvement activities. Discussion: Our study will evaluate the effect of a HBB/ENC training and quality monitoring and improvement package on perinatal mortality using a large multicenter design and approach in 71 resource-limited health facilities, leveraging an existing birth registry to provide neonatal outcomes through day 7. The study will provide the evidence base, lessons learned, and best practices that will be essential to guiding future policy and investment in neonatal resuscitation. Trial registration: Trial registration ClinicalTrials.gov Identifier: NCT0168101

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network´s (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health.Fil: Goudar, Shivaprasad S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Stolka, Kristen B.. Research Triangle Institute International; Estados UnidosFil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Honnungar, Narayan V.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Mastiholi, Shivanand C.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Ramadurg, Umesh Y.. S. Nijalingappa Medical College; IndiaFil: Dhaded, Sangappa M.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Pasha, Omrana. Aga Khan University; PakistánFil: Patel, Archana. Indira Gandhi Government Medical College and Lata Medical Research Foundation; IndiaFil: Esamai, Fabian. University School of Medicine; KeniaFil: Chomba, Elwyn. University of Zambia; ZambiaFil: Garces, Ana. Universidad de San Carlos; GuatemalaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Carlo, Waldemar A.. University of Alabama at Birmingahm; Estados UnidosFil: Goldenberg, Robert L.. Columbia University; Estados UnidosFil: Hibberd, Patricia L.. Massachusetts General Hospital for Children; Estados UnidosFil: Liechty, Edward A.. Indiana University; Estados UnidosFil: Krebs, Nancy F.. University of Colorado School of Medicine; Estados UnidosFil: Hambidge, Michael K.. University of Colorado School of Medicine; Estados UnidosFil: Moore, Janet L.. Research Triangle Institute International; Estados UnidosFil: Wallace, Dennis D.. Research Triangle Institute International; Estados UnidosFil: Derman, Richard J. Christiana Care Health Services; Estados UnidosFil: Bhalachandra, Kodkany S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Bose, Carl L.. University of North Carolina; Estados Unido

Challenge of Reducing Perinatal Mortality in Rural Congo: Findings of a Prospective, Population-based Study

Each year, an estimated six million perinatal deaths occur worldwide, and 98% of these deaths occur in lowand middle-income countries. These estimates are based on surveys in both urban and rural areas, and they may underrepresent the problem in rural areas. This study was conducted to quantify perinatal mortality, to identify the associated risk factors, and to determine the most common causes of early neonatal death in a rural area of the Democratic Republic of the Congo (DRC). Data were collected on 1,892 births. Risk factors associated with perinatal deaths were identified using multivariate analysis with logistic regression models. Causes of early neonatal deaths were determined by physician-review of information describing death. The perinatal mortality rate was 61 per 1,000 births; the stillbirth rate was 30 per 1,000 births; and the early neonatal death rate was 32 per 1,000 livebirths. Clinically-relevant factors independently associated with perinatal death included: low birthweight [odds ratio (OR)=13.51, 95% confidence interval (CI) 7.82-23.35], breech presentation (OR)=12.41; 95% CI 4.62-33.33), lack of prenatal care (OR=2.70, 95% CI 1.81-4.02), and parity greater than 4 (OR=1.93 95% CI 1.11-3.37). Over one-half of early neonatal deaths (n=37) occurred during the first two postnatal days, and the most common causes were low birthweight/prematurity (47%), asphyxia (34%), and infection (8%). The high perinatal mortality rate in rural communities in the DRC, approximately one-half of which is attributable to early neonatal death, may be modifiable. Specifically, deaths due to breech presentation, the second most common risk factor, may be reduced by making available emergency obstetric care. Most neonatal deaths occur soon after birth, and nearly three-quarters are caused by low birthweight/prematurity or asphyxia. Neonatal mortality might be reduced by targeting interventions to improve neonatal resuscitation and care of larger preterm infants

Trends and determinants of stillbirth in developing countries: results from the Global Network\u27s Population-Based Birth Registry.

BACKGROUND: Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten-fold higher than in high-income countries. The United Nations\u27 Every Newborn Action Plan has set a goal of 12 stillbirths per 1000 births by 2030 for all countries. METHODS: From a population-based pregnancy outcome registry, including data from 2010 to 2016 from two sites each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of annual decline as well as risk factors for 427,111 births of which 12,181 were stillbirths. RESULTS: The mean stillbirth rates for the sites were 21.3 per 1000 births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per 1000 births for an average annual decline of 3.0%. Risk factors for stillbirth were similar across the sites and included maternal age \u3c 20 years and age \u3e 35 years. Compared to parity 1-2, zero parity and parity \u3e 3 were both associated with increased stillbirth risk and compared to women with any prenatal care, women with no prenatal care had significantly increased risk of stillbirth in all sites. CONCLUSIONS: At the current rates of decline, stillbirth rates in these sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by 2030. More attention to the risk factors and treating the causes of stillbirths will be required to reach the Every Newborn Action Plan goal of stillbirth reduction. TRIAL REGISTRATION: NCT01073475

A pre-post study of a multi-country scale up of resuscitation training of facility birth attendants: does Helping Babies Breathe training save lives?

Background: Whether facility-based implementation of Helping Babies Breathe (HBB) reduces neonatal mortality at a population level in low and middle income countries (LMIC) has not been studied. Therefore, we evaluated HBB implementation in this context where our study team has ongoing prospective outcome data on all pregnancies regardless of place of delivery. Methods: We compared outcomes of birth cohorts in three sites in India and Kenya pre-post implementation of a facility-based intervention, using a prospective, population-based registry in 52 geographic clusters. Our hypothesis was that HBB implementation would result in a 20 % decrease in the perinatal mortality rate (PMR) among births ≥1500 g. Results: We enrolled 70,704 births during two 12-month study periods. Births within each site did not differ prepost intervention, except for an increased proportion ofbirths; however, a post-hoc analysis stratified by birthweight documented improvement insurvival. Conclusions: Rapid scale up of HBB training of facility birth attendants in three diverse sites in India and Kenya was not associated with consistent improvements in mortality among all neonates ≥1500 g; however, differential improvements inpopulation, data collection, and ongoing quality monitoring activities. Trial registration: The study was registered at ClinicalTrials.gov: NCT0168101