William J. Keenan

Neonatal resuscitation in low-resource settings: What, who, and how to overcome challenges to scale up?

Each year approximately 10 million babies do not breathe immediately at birth, of which about 6 million require basic neonatal resuscitation. The major burden is in low‐income settings, where health system capacity to provide neonatal resuscitation is inadequate.

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

BackgroundOf 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.ObjectiveTo 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.MethodsWe 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.ResultsWe 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.ConclusionNeonatal 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.FundingThis 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.

Reducing intrapartum-related neonatal deaths in low- and middle-income countries-what works?

Each year, 814,000 neonatal deaths and 1.02 million stillbirths result from intrapartum-related causes, such as intrauterine hypoxia. Almost all of these deaths are in low- and middle-income countries, where women frequently lack access to quality perinatal care and may delay care-seeking. Approximately 60 million annual births occur outside of health facilities, and most of these childbirths are without a skilled birth attendant. Conditions that increase the risk of intrauterine hypoxia--such as pre-eclampsia/eclampsia, obstructed labor, and low birth weight--are often more prevalent in low resource settings. Intrapartum-related neonatal deaths can be averted by a range of interventions that prevent intrapartum complications (eg, prevention and management of pre-eclampsia), detect and manage intrapartum problems (eg, monitoring progress of labor with access to emergency obstetrical care), and identify and assist the nonbreathing newborn (eg, stimulation and bag-mask ventilation). Simple, affordable, and effective approaches are available for low-resource settings, including community-based strategies to increase skilled birth attendance, partograph use by frontline health workers linked to emergency obstetrical care services, task shifting to increase access to Cesarean delivery, and simplified neonatal resuscitation training (Helping Babies Breathe(SM)). Coverage of effective interventions is low, however, and many opportunities are missed to provide quality care within existing health systems. In sub-Saharan Africa, recent health services assessments found only 15% of hospitals equipped to provide basic neonatal resuscitation. In the short term, intrapartum-related neonatal deaths can be substantially reduced by improving the quality of services for all childbirths that occur in health facilities, identifying and addressing the missed opportunities to provide effective interventions to those who seek facility-based care. For example, providing neonatal resuscitation for 90% of deliveries currently taking place in health facilities would save more than 93,000 newborn lives each year. Longer-term strategies must address the gaps in coverage of institutional delivery, skilled birth attendance, and quality by strengthening health systems, increasing demand for care, and improving community-based services. Both short- and long-term strategies to reduce intrapartum-related mortality should focus on reducing inequities in coverage and quality of obstetrical and perinatal care.

Helping Babies Breathe: global neonatal resuscitation program development and formative educational evaluation.

OBJECTIVES To develop an educational program designed to train health care providers in resource limited settings to carry out neonatal resuscitation. We analyzed facilitator and learner perceptions about the course, examined skill performance, and assessed the quality of instruments used for learner evaluation as part of the formative evaluation of the educational program Helping Babies Breathe. METHODS Multiple stakeholders and a Delphi panel contributed to program development. Training of facilitators and learners occurred in global field test sites. Course evaluations and focus groups provided data on facilitator and learner perceptions. Knowledge and skill assessments included pre/post scores from multiple choice questions (MCQ) and post-training assessment of bag and mask skills, as well as 2 objective structured clinical evaluations (OSCE). RESULTS Two sites (Kenya and Pakistan) trained 31 facilitators and 102 learners. Participants expressed high satisfaction with the program and high self-efficacy with respect to neonatal resuscitation. Assessment of participant knowledge and skills pre/post-program demonstrated significant gains; however, the majority of participants could not demonstrate mastery of bag and mask ventilation on the post-training assessment without additional practice. CONCLUSIONS Participants in a program for neonatal resuscitation in resource-limited settings demonstrated high satisfaction, high self-efficacy and gains in knowledge and skills. Mastery of ventilation skills and integration of skills into case management may not be achievable in the classroom setting without additional practice, continued learning, and active mentoring in the workplace. These findings were used to revise program structure, materials and assessment tools.

Stillbirth and Newborn Mortality in India After Helping Babies Breathe Training

OBJECTIVE: This study evaluated the effectiveness of Helping Babies Breathe (HBB) newborn care and resuscitation training for birth attendants in reducing stillbirth (SB), and predischarge and neonatal mortality (NMR). India contributes to a large proportion of the worlds annual 3.1 million neonatal deaths and 2.6 million SBs. METHODS: This prospective study included 4187 births at >28 weeks’ gestation before and 5411 births after HBB training in Karnataka. A total of 599 birth attendants from rural primary health centers and district and urban hospitals received HBB training developed by the American Academy of Pediatrics, using a train-the-trainer cascade. Pre-post written trainee knowledge, posttraining provider performance and skills, SB, predischarge mortality, and NMR before and after HBB training were assessed by using χ2 and t-tests for categorical and continuous variables, respectively. Backward stepwise logistic regression analysis adjusted for potential confounding. RESULTS: Provider knowledge and performance systematically improved with HBB training. HBB training reduced resuscitation but increased assisted bag and mask ventilation incidence. SB declined from 3.0% to 2.3% (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59–0.98) and fresh SB from 1.7% to 0.9% (OR 0.54, 95% CI 0.37–0.78) after HBB training. Predischarge mortality was 0.1% in both periods. NMR was 1.8% before and 1.9% after HBB training (OR 1.09, 95% CI 0.80–1.47, P = .59) but unknown status at 28 days was 2% greater after HBB training (P = .007). CONCLUSIONS: HBB training reduced SB without increasing NMR, indicating that resuscitated infants survived the neonatal period. Monitoring and community-based assessment are recommended.

Parathyroid function in infants of diabetic mothers

Serum parathyroid hormone and total and ionized Ca, Mg, and P levels were determined serially from birth to 96 hr of age in 28 infants of diabetic mothers (IDM, 15 Class A, 13 Class B, C, D) and their respective mothers at the time of delivery. In spite of marked decreases in concentrations of serum total and ionized Ca from birth to 24 to 48 hr, there was an insignificant increase in serum PTH values over this period in infants of insulin-dependent mothers. Infants of Class A diabetic mothers had an equivocal PTH response. Nineteen term control infants were similarly examined and had a significant increase in serum PTH postnatally. Relatively higher values of serum ionized Ca at birth in IDM were followed by greater decreases in ionized Ca from birth to 24-48 hr of age, and by decreased neonatal parathyroid function. The data support functional hypoparathyroidism as a basis for the hypocalcemia and hyperphosphatemia of IDM. It is speculated that increased concentrations of serum ionized Ca in utero and suppression of activity in the fetal parathyroid glands may be a cause for the functional hypoparathyroidism.

Group B streptococcus and early-onset sepsis in the era of maternal prophylaxis.

Despite an era of marked success with universal screening, Group B Streptococcus (GBS) continues to be an important cause of early-onset sepsis, and thus remains a significant public health issue. Improved eradication of GBS colonization and disease may involve universal screening in conjunction with rapid diagnostic technologies or other novel approaches. Given the complications and potential limitations associated with maternal intrapartum prophylaxis, however, vaccines may be the most effective means of preventing neonatal GBS disease. The global utility of conjugated GBS vaccines may be hampered by the variability of serotypes in diverse populations and geographic locations. Modern technologies, such as those involving proteomics and genomic sequencing, are likely to hasten the development of a universal vaccine against GBS.

Reducing maternal, newborn, and infant mortality globally: an integrated action agenda.

There has been increasing awareness over recent years of the persisting burden of worldwide maternal, newborn, and child mortality. The majority of maternal deaths occur during labor, delivery, and the immediate postpartum period, with obstetric hemorrhage as the primary medical cause of death. Other causes of maternal mortality include hypertensive diseases, sepsis/infections, obstructed labor, and abortion‐related complications. Recent estimates indicate that in 2009 an estimated 3.3 million babies died in the first month of life and that overall, 7.3 million children under 5 die each year. Recent data also suggest that sufficient evidence‐ and consensus‐based interventions exist to address reproductive, maternal, newborn, and child health globally, and if implemented at scale, these have the potential to reduce morbidity and mortality. There is an urgent need to put elements in place to promote integrated interventions among healthcare professionals and their associations. What is needed is the political will and partnerships to implement evidence‐based interventions at scale.

Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns

Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic modality for newborn respiratory failure, but there is little information available regarding the prognostic determinants with this technique. One hundred thirty-five newborns treated with ECMO over a 4-year period were critically analyzed with regard to the influence that birth weight, gestational age, age at initiation of ECMO, best blood gases before ECMO, number of hours on ECMO, renal failure, intracerebral hemorrhage, and long-distance air transport had on survival. Infants with meconium aspiration and those undergoing long-distance transfer showed significant differences in blood gases before ECMO, with survivors having more normal pH and carbon dioxide tension values. Intracerebral hemorrhage and renal failure that developed during ECMO were grave prognostic signs, with few survivors in either group. These data show that ability to ventilate patients before ECMO, giving normal carbon dioxide tension and pH values, is an important prognostic sign in infants with meconium aspiration and undergoing long-distance transfer for ECMO, whereas renal failure and intracerebral hemorrhage are usually lethal complications of ECMO. Each center performing ECMO should continually reevaluate this invasive technique and its results and complications.

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013–2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.