Despite the wide acceptance of neonatal resuscitation as a standard of care, there is limited evidence of its impact on neonatal outcomes, in part due to the ethical challenges of undertaking individually randomized RCTs. To our knowledge, this is the first systematic review, meta-analysis and expert panel convened to provide estimates of the reduction in neonatal mortality that could be achieved through neonatal resuscitation training. Immediate assessment and stimulation of the newborn is more feasible without equipment or skilled workers. Our expert panel estimated that this simple action could reduce both term intrapartum-related (ie. “birth asphyxia”) and preterm mortality by 10%. Our meta-analysis suggests that neonatal resuscitation training in facilities was associated with an additional 30% reduction in intrapartum-related neonatal mortality. Studies have not consistently assessed the effects on preterm deaths, and there is no high or moderate quality evidence addressing this; expert opinion estimated a 10% reduction in prematurity-related neonatal deaths following resuscitation in health facilities. Current evidence for neonatal resuscitation in community settings is heterogeneous, and experts estimated a 20% reduction in term intrapartum-related deaths and 5% reduction in deaths attributed to preterm birth for community-based resuscitation either with a midwife alone at home or a TBA.
Simple immediate newborn assessment and warming, drying and tactile stimulation is the first step of neonatal resuscitation and was estimated by experts to result in a small (10%) reduction in intrapartum-related (“birth asphyxia”) and preterm deaths. In resource limited settings, these simple initial steps are feasible to be performed by a family member or primary healthcare provider with minimal skills – for example, rubbing the baby dry with a cloth– and might save lives, but this is expected to have limited effect. Observational studies suggest that between 6-42% of newborns who do not breathe at birth require ventilation [2, 54, 55], indicating that the majority of non-breathing babies may respond to simple steps alone. Although the anticipated mortality impact is low, the cost is also likely to be low as no equipment is required.
Our meta-analyses evaluating the impact of facility-based neonatal resuscitation training included low quality before-after studies, but at least comparable in intervention and outcome definitions for intrapartum-related and early neonatal mortality. Consistent effect sizes were observed for intrapartum-related mortality and all cause early neonatal mortality. The China NRP study  was excluded but it is notable that the reduction in labour room mortality for term babies (33%) was of similar magnitude. It is disappointing that the majority of the 16 facility studies identified did not meet inclusion criteria. However, given mortality effect consistency across the studies and generalizability to low-middle income countries, applying adapted GRADE criteria the evidence level was moderate (table 7). For all included studies, the comparison groups involved some pre-training management of the non-breathing baby, thus, these estimates reflect the impact of additional training for resuscitation, incremental to immediate newborn assessment and stimulation. Implementing basic neonatal resuscitation in a setting where no simple immediate newborn care is in place, such as peripheral maternity clinics, may have a greater effect. On the other hand, some of the effect may have been due to improved post-resuscitation care in two of the studies [2, 44]. While some data was available on the impact of facility-based resuscitation on preterm mortality, the data was too heterogeneous to pool. However, there is strong biologic plausibility that resuscitation may reduce mortality in moderate-late preterms who require minimal assistance with positive-pressure ventilation to initiate breathing, without requiring ongoing assisted ventilation; experts estimated a10% effect at facility level.
The impact of resuscitation training may be greater in higher mortality settings where obstetric care is more limited. In Bulgaria, an upper-middle income country where the baseline intrapartum-related mortality was relatively low, the estimated effect was smaller (16%) than in higher mortality settings such as Zambia and India, where neonatal resuscitation training was associated with a 30-43% reduction in intrapartum-related mortality. In settings with high coverage of high quality intrapartum management, the majority of term infants who die from intrapartum-related causes may be severely asphyxiated infants who require interventions beyond neonatal resuscitation alone, such as ongoing ventilation and therapeutic hypothermia.
The evidence for basic resuscitation in community settings was too heterogeneous to combine: study designs varied substantially, resuscitation training was one of numerous interventions in newborn care packages, and the outcome measure of cause-specific mortality differed across studies, often reflecting reduction in other causes of death such as preterm birth and infections. Significant reductions in all-cause neonatal or perinatal mortality were observed in 4 studies, ranging from 25-61% [5, 53–55], and reported “asphyxia” specific mortality was reduced in four studies, ranging from 61-70% [5, 53–55]. In the multi-center “First Breath” study , although no overall impact on PMR was observed, there was a significant 19% PMR reduction for deliveries with trained birth attendants, and a reduction in intrapartum-related morbidity (prevalence of 5 minute Apgar scores <4 and abnormal neurologic exams at 7 days). On the other hand, preliminary results from a cRCT in Bangladesh failed to demonstrate a reduction in ENMR with the additional training of TBAs in bag-mask resuscitation beyond immediate care and mouth-to-mouth resuscitation. Although it was not possible to derive a cause-specific mortality estimate from existing evidence, our expert panel agreed on the presence of an effect (20% for intrapartum-related mortality, 5% for preterm mortality), albeit slightly smaller than for facility based resuscitation, reflecting the additional challenges in implementation in such contexts, with a single provider and variable cadres. There is a need for consistency in future studies with respect to intervention content, study design, outcome measurement and definitions in order to more precisely evaluate the potential impact of resuscitation training at community level.
Important programmatic considerations for resuscitation training in resource limited settings include the benefit of teaching advanced procedures, provider competency, and skill maintenance. Two of the studies in our meta-analysis included some aspects of advanced neonatal resuscitation; however, advanced procedures are more complex to teach (i.e. chest compressions, intubation, or medications) and are required for ~2% of all babies who do not breathe at birth[2, 56], and fewer than 1% of all babies born[6, 11]. Basic neonatal resuscitation is sufficient for most babies who would be saved by resuscitation in low-middle income settings, and the additional benefit of advanced procedures is likely to be low. For the purposes of this LiST estimate, the effect of facility based neonatal resuscitation was assumed to be achievable with basic neonatal resuscitation, which is the clear priority for rapid scale up in facilities in low and middle income countries, given feasibility, skills required, and equipment costs. Furthermore, training programs should emphasize routine assessment of provider knowledge, competency and skill maintenance. Provider knowledge and performance skills to conduct resuscitation decline significantly over time. Regular refresher training programs, practice drills, and DVD videos of resuscitation are methods of ensuring skill maintenance and program effectiveness[1, 58] .
A reduction in stillbirth rate has been observed in 2 community-based studies, after training programs including bag-mask resuscitation [5, 52]. A live newborn with severe neonatal depression is difficult to distinguish from a stillborn, and there is the potential for misclassification in low-resource settings where newborns are not typically assessed for signs of life at birth (particularly heart rate) [59, 60]. In addition to reducing misclassification, training in neonatal assessment and resuscitation may also increase survival in apparently stillborn infants (Apgar score assessed as 0 at 1 minute). Among apparently stillbirth infants who were resuscitated, case fatality ranges between 16-65% in high income settings [61–63], with major intensive care support, and long term outcomes that are significantly worse than for resuscitated babies who did have a heart rate detected . These findings emphasize the need to accurately count stillbirths and assess long term outcomes to capture the full impact of obstetric and immediate newborn care interventions [65, 66].
Consistent case definitions are required for comparable population-level surveillance of disease burden and for evaluation of intervention effectiveness. A survey of policy makers revealed that “confusing terminology” and “lack of valid measurement indicators at the community level” were key barriers to obtaining the necessary information to make policy decisions. Recent advances have been made in case definitions and verbal autopsy hierarchies to distinguish intrapartum-related events in term or almost term babies from preterm babies, although the issue of distinguishing growth restricted infants remains a challenge and is especially important in South Asia. Consistent use of such verbal autopsy tools, and more importantly the hierarchies, is critical . This review emphasizes the need to minimize misclassification of live births as stillbirths, and to apply standardized definitions for intrapartum-related neonatal deaths, as opposed to clinical definitions such as “birth asphyxia.” Definitions and measurement varied across studies and between facility and community/home-based studies. Even in facility settings, the few studies that reported preterm mortality used inconsistent birth weight and gestational age cut-offs. There is a marked lack of data regarding effect of resuscitation on preterm babies. The long-term developmental outcomes following resuscitation also require further research. Particularly in low-middle resource settings, where health systems and families have limited resources to care for survivors with chronic disability, there is a dearth of comparable long term developmental outcome data (ACL, personal communication for CHERG/GBD neonatal encephalopathy estimates group).
This review has important implications for the scale up of neonatal resuscitation. The immediate opportunity is for facility based resuscitation. Even in facilities, equipment is lacking and few providers are trained in neonatal resuscitation. In 6 African national service provision assessments (DHS Macro), between 2-12% of delivery staff had been trained in neonatal resuscitation and fewer than one quarter of hospitals had newborn bag-masks available . Given these challenges, achieving high coverage with basic neonatal resuscitation should be prioritized, as advanced resuscitation is infrequently required and may have limited additional mortality impact in low-resource settings. Establishing resuscitation training for pre-service education of midwives, doctors and nurses who provide newborn care is a crucial step. Recent advances in simpler training and robust, low cost equipment hold great promise for rapid scale up at much lower cost . Furthermore, for the 60 million births a year outside facilities, while implementing basic neonatal resuscitation at the community level is controversial, there may be a role in some high-mortality settings where most births occur at home, skilled attendance is not achievable in the foreseeable future, alternative cadres already attend the majority of deliveries, and the case load per attendant is high enough to justify the training, equipment inputs and skill maintenance.