Effectiveness of Neonatal Resuscitation Training Programs, Implementation, and Scale-Up in Low- and Middle-Income Countries
In 2020, 2.4 million newborns died globally , illustrating the vulnerability newborns experience within the first 28 days of life. While the rate of under-5 deaths has decreased since 1990, neonatal mortality has failed to decrease at the same rate and accounts for 47% of under-5 deaths . Intrapartum-related complications, such as birth asphyxia or the inability to breathe at birth, account for one of the leading causes of these global newborn deaths. Specifically, approximately 5–10% of newborns require assistance at birth to begin breathing  and approximately 25% of all neonatal deaths are caused by asphyxia . The majority of deaths caused by asphyxia occur in low- and middle-income countries (LMICs), where access to obstetric care is limited . For example, Sub-Saharan Africa, and Central and Southern Asia account for the highest neonatal mortality rates globally at 43% (27 deaths per 1,000 live births) and 36% (23 deaths per 1,000 live births), respectively . In comparison, high-income countries have an average mortality rate of three deaths per 1,000 live births . To improve newborn survival, neonatal resuscitation (NR) has been found to be effective in preventing a large proportion of these deaths, reducing mortality due to birth asphyxia by 30% . A neonatal resuscitation training program (NRTP) involves a set of interventions delivered at birth to support the initiation of breathing . Basic resuscitation involves airway clearing (i.e., suctioning), head positioning, positive-pressure ventilation (i.e., bag-and-mask ventilation), stimulation, and drying and is effective for most neonates with secondary apnoea . Advanced resuscitation is necessary for approximately 1% of births and involves chest compression, intubation, or medications . In instances where advanced resuscitation is needed, the baby will often require ongoing support and intensive care. NRTPs generally involve multiple health providers with extensive training and access to advanced technology. As such, the currently accepted standard of NRTP took decades to become a reality for high-income countries and continues to be a challenge to implement for low-resource countries . To improve the situation, numerous educational programs have been designed to train health care providers in NR. The standardized American Academy of Pediatrics (AAP) Neonatal Resuscitation Program (NRP) was the first such programme developed in 1987 in the USA. The NRP is responsible for standardizing the approach to resuscitation through training that provides both the knowledge and the skills required for resuscitation . Globally used, the programme is taught in over 140 countries and is based upon the best currently available evidence . However, as the rates of neonatal mortality in LMICs continued to soar despite the widespread use of the NRP, an alternative standardized approach was deemed necessary to improve implementation of learned skills within clinical practice, specifically in low-resource settings. To address the need for a NRTP that was tailored to low-resource settings, the AAP developed the 2010 Helping Babies Breathe (HBB) program . The approval of the HBB program sparked at a time when the International Liaison Committee on Resuscitation (ILCOR) changed its recommendation of using 100% oxygen for NR to room air since 100% oxygen during resuscitation was proven to cause oxidative stress, leading to increased risk of mortality or neurological damage. This was an important shift, as supplying 100% oxygen in NR care settings would have been a barrier to the scale-up and implementation of the HBB program in LMICs. HBB emphasizes knowledge building with pictures and low-cost inflatable mannequins and is focused on establishing ventilation in newborns within the first 60 s of life . However, evidence on the effectiveness of the HBB program in reducing neonatal mortality has been mixed , and it has been well documented that skills and knowledge retention after training tend to decrease with time . As such, there is a need to determine which NRTPs are the most effective in LMICs using more recent evidence regarding neonatal mortality and morbidity, in addition to outcomes related to retention of knowledge and skills by birth attendants. Consonant with determining the most effective and cost-effective NRTPs for LMIC settings, the challenge to achieving impact becomes scaling-up training to provide universal coverage for basic resuscitation in these resource-limited settings. There has been a transition in place of births and hence location of resuscitation needs globally. While the majority of births in LMICs previously occurred in home settings, approximately 80% of births now occur in facility-based settings . Previous studies have reported that reductions in mortality outcomes are more common in secondary care facilities, compared to lower level facilities, as they are better equipped to provide more advanced care and have more staff per bed . Therefore, to achieve universal coverage, a better understanding of the strengths and challenges of current NRTPs is needed to inform scale-up across low-resource settings. Objective The purpose of this paper was to synthesize the current evidence regarding NRTPs and scale-up of these programs, which has contributed to the upcoming Lancet Global Newborn Care Series 2025, and forms part of a supplement describing an extensive synthesis of the evidence on effective newborn interventions in LMICs. This manuscript will contribute to a forthcoming Lancet Global Newborn Care Series 2025s key message and strategies regarding effectiveness of interventions for asphyxia management, which will help progress goals in reducing neonatal mortality. The following two review questions were assessed: 1. What are the most effective NRTPs for improving mortality and morbidity outcomes in newborns, and knowledge and skill retention in health care providers in LMICs? 2. What are effective implementation strategies for the roll-out and scale-up of NRTPs in LMICs? 

The purpose of this paper was to synthesize the current evidence regarding NRTPs and scale-up of these programs, which has contributed to the upcoming Lancet Global Newborn Care Series 2025, and forms part of a supplement describing an extensive synthesis of the evidence on effective newborn interventions in LMICs. This manuscript will contribute to a forthcoming Lancet Global Newborn Care Series 2025s key message and strategies regarding effectiveness of interventions for asphyxia management, which will help progress goals in reducing neonatal mortality. The following two review questions were assessed: 1. What are the most effective NRTPs for improving mortality and morbidity outcomes in newborns, and knowledge and skill retention in health care providers in LMICs? 2. What are effective implementation strategies for the roll-out and scale-up of NRTPs in LMICs? 

For topics regarding NRTP effectiveness and scale-up, we were unable to identify any recent systematic reviews of relevance, thus new systematic reviews were conducted. Herein, we provide a high-level summary of the review methodology per review topic; however, a detailed summary of all methods can be referenced here . Search Strategy NRTP effectiveness and scale-up studies were searched in Medline, Embase, CINAHL, Cochrane CENTRAL, and Global Index Medicus databases in August 2022. Additional studies were found and added through snowballing and grey literature searches. There were no limitations on geographical setting or publication language for both reviews. All search strategies can be found in supplementary material A (for all online suppl. material, see https://doi.org/10.1159/000542539 ). Search Selection This review was limited to studies conducted in LMICs only. The target population was primarily focused on newborns; however, we were also interested in understanding the impact of NRTPs on healthcare professionals’ knowledge and skill acquisition. The first research question was strictly focused on effectiveness and therefore only included randomized controlled trials (RCTs) or quasi-experimental studies, whereas the NRTP scale-up question included a broader scope of study designs to ensure the capture of implementation and cost-analysis research. Studies reporting on non-NR specific training programs where the effect of NR training outcomes could not be disaggregated from outcomes associated with broad, integrated packages on maternal and child health, were excluded. See for inclusion criteria per topic. Statistical Analyses For the topic of NRTP effectiveness, we performed standard meta-analyses to generate a summary risk ratio (RR) and 95% confidence interval (CI) for each dichotomous outcome. For continuous outcomes, a mean difference was calculated if studies used the same scale to assess the outcome or a standardized mean difference (SMD) if studies used different scales to assess the outcome and 95% CI. Due to heterogeneity across studies, a random-effects model was used for all pooled estimates. The inverse variance method was used as the default for all analyses, except when dichotomous data were sparse in terms of low event rate or small study size, in which case we used the Mantel-Haenszel method. When a study had multiple arms that received different interventions of interest, they were both included in the meta-analyses as separate intervention-control comparisons. Findings from non-randomized controlled trials, controlled pre-post studies, and interrupted time-series designs were analysed and reported separately. Studies that randomized participants at the cluster level were adjusted for clustering by reducing the size of the trial to its effective sample size or by inflating the standard error. We did not make these adjustments if the study authors reported they had adjusted for clustering already. Studies reporting a standard error were converted to standard deviation using Cochrane methods . Knowledge, skill, and self-efficacy outcomes were pooled across studies by converting numerical scales and mean values to percent values for analysis. Self-efficacy was defined as a healthcare provider’s level of confidence in their ability to effectively resuscitate a newborn according to NRTP guidance. Very early neonatal and perinatal mortality were defined as death within 24 h, whereas early neonatal and perinatal mortality were defined as death after 24 h to 7 days. Additional, non-time dependent mortality outcomes included stillbirths, fresh stillbirths, macerated stillbirths, perinatal mortality, mortality due to asphyxia, and all-cause neonatal mortality. Sensitivity analysis by quality assessment was considered, such that any study assessed as high risk using the ROB tool 2.0, serious risk using the ROBINS-I tool, or poor quality using the NIH tool or CASP tool were excluded in the effect estimate. Subgroup analyses were conducted for primary outcomes according to a priori defined sources of potential clinical and methodological heterogeneity for NRTP effectiveness: study design (i.e., pre-post data from non-randomized one-arm trial and pre-post data from one or more arms of a randomized trial); World Health Organization (WHO) region (i.e., Africa, the Americas, South-East Asia, Europe, Eastern-Mediterranean, and Western Pacific); simulation (i.e., simulation and no simulation); standardization (i.e., standardized and no standardization); duration of program (e.g., 2-day training program); and type of provider (i.e., nurses, midwives, birth attendants, physicians, and healthcare students). Given the shift from home-based to facility-based births, a growing interest in the impact of NRTPs at different levels of care has emerged. Thus, subgroup analyses were conducted by level of care (i.e., community, primary, secondary, and tertiary facility settings). Given the plethora of data, we report all pooled estimates for totals and subgroup analyses by level of care for three comparisons assessing NRTP effectiveness (i.e., Any NRTP vs. no NRTP; HBB vs. no HBB; NRP vs. no NRP) in the main text while all other subgroup analyses and comparisons can be found in online supplementary material B. For the topic of NRTP scale-up review, data from included studies were inappropriate for meta-analysis. Therefore, results were narratively summarized and tabulated. See the methods paper for further detail on data extraction, methodological quality assessment, synthesis, and analysis methods . 

NRTP effectiveness and scale-up studies were searched in Medline, Embase, CINAHL, Cochrane CENTRAL, and Global Index Medicus databases in August 2022. Additional studies were found and added through snowballing and grey literature searches. There were no limitations on geographical setting or publication language for both reviews. All search strategies can be found in supplementary material A (for all online suppl. material, see https://doi.org/10.1159/000542539 ). 

This review was limited to studies conducted in LMICs only. The target population was primarily focused on newborns; however, we were also interested in understanding the impact of NRTPs on healthcare professionals’ knowledge and skill acquisition. The first research question was strictly focused on effectiveness and therefore only included randomized controlled trials (RCTs) or quasi-experimental studies, whereas the NRTP scale-up question included a broader scope of study designs to ensure the capture of implementation and cost-analysis research. Studies reporting on non-NR specific training programs where the effect of NR training outcomes could not be disaggregated from outcomes associated with broad, integrated packages on maternal and child health, were excluded. See for inclusion criteria per topic. 

For the topic of NRTP effectiveness, we performed standard meta-analyses to generate a summary risk ratio (RR) and 95% confidence interval (CI) for each dichotomous outcome. For continuous outcomes, a mean difference was calculated if studies used the same scale to assess the outcome or a standardized mean difference (SMD) if studies used different scales to assess the outcome and 95% CI. Due to heterogeneity across studies, a random-effects model was used for all pooled estimates. The inverse variance method was used as the default for all analyses, except when dichotomous data were sparse in terms of low event rate or small study size, in which case we used the Mantel-Haenszel method. When a study had multiple arms that received different interventions of interest, they were both included in the meta-analyses as separate intervention-control comparisons. Findings from non-randomized controlled trials, controlled pre-post studies, and interrupted time-series designs were analysed and reported separately. Studies that randomized participants at the cluster level were adjusted for clustering by reducing the size of the trial to its effective sample size or by inflating the standard error. We did not make these adjustments if the study authors reported they had adjusted for clustering already. Studies reporting a standard error were converted to standard deviation using Cochrane methods . Knowledge, skill, and self-efficacy outcomes were pooled across studies by converting numerical scales and mean values to percent values for analysis. Self-efficacy was defined as a healthcare provider’s level of confidence in their ability to effectively resuscitate a newborn according to NRTP guidance. Very early neonatal and perinatal mortality were defined as death within 24 h, whereas early neonatal and perinatal mortality were defined as death after 24 h to 7 days. Additional, non-time dependent mortality outcomes included stillbirths, fresh stillbirths, macerated stillbirths, perinatal mortality, mortality due to asphyxia, and all-cause neonatal mortality. Sensitivity analysis by quality assessment was considered, such that any study assessed as high risk using the ROB tool 2.0, serious risk using the ROBINS-I tool, or poor quality using the NIH tool or CASP tool were excluded in the effect estimate. Subgroup analyses were conducted for primary outcomes according to a priori defined sources of potential clinical and methodological heterogeneity for NRTP effectiveness: study design (i.e., pre-post data from non-randomized one-arm trial and pre-post data from one or more arms of a randomized trial); World Health Organization (WHO) region (i.e., Africa, the Americas, South-East Asia, Europe, Eastern-Mediterranean, and Western Pacific); simulation (i.e., simulation and no simulation); standardization (i.e., standardized and no standardization); duration of program (e.g., 2-day training program); and type of provider (i.e., nurses, midwives, birth attendants, physicians, and healthcare students). Given the shift from home-based to facility-based births, a growing interest in the impact of NRTPs at different levels of care has emerged. Thus, subgroup analyses were conducted by level of care (i.e., community, primary, secondary, and tertiary facility settings). Given the plethora of data, we report all pooled estimates for totals and subgroup analyses by level of care for three comparisons assessing NRTP effectiveness (i.e., Any NRTP vs. no NRTP; HBB vs. no HBB; NRP vs. no NRP) in the main text while all other subgroup analyses and comparisons can be found in online supplementary material B. For the topic of NRTP scale-up review, data from included studies were inappropriate for meta-analysis. Therefore, results were narratively summarized and tabulated. See the methods paper for further detail on data extraction, methodological quality assessment, synthesis, and analysis methods . 

Study Inclusion Both reviews generated a total of 2,224 records. After removing duplicates, 1,684 records were screened, of which 358 records were included for full-text analysis. Of these, 65 records met the eligibility criteria for NRTP effectiveness and 39 records for NRTP scale-up. These totals include 11 overlapping studies which met the eligibility criteria for NRTP effectiveness and scale-up. Therefore, only 93 unique records were included in our analyses across both reviews . Study Characteristics of Included Studies The 93 unique studies included 50 quasi-experimental studies, 18 randomized controlled studies, 11 observational and cross-sectional studies, seven mixed methods studies, three qualitative studies, two implementation studies, and two cost-analysis studies . Of the 93 included studies, five studies were implemented at a community-level, 12 studies were implemented at a primary-level, 29 studies were implemented at a secondary-level, 19 studies were implemented at a tertiary-level, and 28 studies were implemented at a mixed-level. Of the 65 included studies for NRTP effectiveness, 29 studies assessed the HBB program compared to no training, 26 studies assessed the NRP compared to no training, and 10 assessed other training programs (see online suppl. material C for a list of all included comparisons; see online suppl. material D for all standardized resuscitation training programs identified within the included studies). The publication year of the included studies ranged from 2001 to 2023. A detailed COIS table can be found for each included study in online supplementary material E. Global maps illustrating the number of studies that implemented NRTP(s) per LMIC can be found in online supplementary material F. Methodological Quality of Included Studies Of the overall 18 RCTs included in this review, one (5.5%) was rated as having a high risk of bias, 10 (55.6%) were rated as having some risk of bias, and seven (38.9%) were rated as having a low risk of bias. Of 50 quasi-experimental included studies, 30 (60%) were rated as having a serious concern, 19 (38%) were rated as having a moderate concern, and one (2%) study was rated as having a low concern. Of 13 observational cohort and cross-sectional included studies, seven (54%) were rated as poor quality, four (31%) were rated as fair quality, and two (15%) were rated as good quality. Of the three qualitative studies included, one (33%) was rated as poor quality, one (33%) was rated as fair quality, and one (33%) was rated as good quality. All nine mixed methods studies were of high quality. See online supplementary material G for a detailed quality assessment rating for each included study. 

Both reviews generated a total of 2,224 records. After removing duplicates, 1,684 records were screened, of which 358 records were included for full-text analysis. Of these, 65 records met the eligibility criteria for NRTP effectiveness and 39 records for NRTP scale-up. These totals include 11 overlapping studies which met the eligibility criteria for NRTP effectiveness and scale-up. Therefore, only 93 unique records were included in our analyses across both reviews . 

The 93 unique studies included 50 quasi-experimental studies, 18 randomized controlled studies, 11 observational and cross-sectional studies, seven mixed methods studies, three qualitative studies, two implementation studies, and two cost-analysis studies . Of the 93 included studies, five studies were implemented at a community-level, 12 studies were implemented at a primary-level, 29 studies were implemented at a secondary-level, 19 studies were implemented at a tertiary-level, and 28 studies were implemented at a mixed-level. Of the 65 included studies for NRTP effectiveness, 29 studies assessed the HBB program compared to no training, 26 studies assessed the NRP compared to no training, and 10 assessed other training programs (see online suppl. material C for a list of all included comparisons; see online suppl. material D for all standardized resuscitation training programs identified within the included studies). The publication year of the included studies ranged from 2001 to 2023. A detailed COIS table can be found for each included study in online supplementary material E. Global maps illustrating the number of studies that implemented NRTP(s) per LMIC can be found in online supplementary material F. 

Of the overall 18 RCTs included in this review, one (5.5%) was rated as having a high risk of bias, 10 (55.6%) were rated as having some risk of bias, and seven (38.9%) were rated as having a low risk of bias. Of 50 quasi-experimental included studies, 30 (60%) were rated as having a serious concern, 19 (38%) were rated as having a moderate concern, and one (2%) study was rated as having a low concern. Of 13 observational cohort and cross-sectional included studies, seven (54%) were rated as poor quality, four (31%) were rated as fair quality, and two (15%) were rated as good quality. Of the three qualitative studies included, one (33%) was rated as poor quality, one (33%) was rated as fair quality, and one (33%) was rated as good quality. All nine mixed methods studies were of high quality. See online supplementary material G for a detailed quality assessment rating for each included study. 

Comparison 1: Post-NR Training Program versus Pre-NR Training Program Knowledge and Skill-Based Outcomes Post-NRTP, participants experienced improvements in mean knowledge test scores, more healthcare providers passed knowledge tests with a score of 75% or higher, and improved self-efficacy compared to pre-NRTP training. However, healthcare providers had borderline significantly higher mean knowledge post-test scores immediately following NR training compared to 3 months later ( p = 0.05). Further, NRTPs also improved both mean composite practical skills and specialized skills (i.e., bag-mask ventilation skills, objective structured clinical examination (OSCE) A and OSCE B skills); however, providers had significantly lower practical skill scores 3- and 6-months later compared to immediately after training . OSCE A and B refer to validated knowledge check questions and simulation tests available in NRTP educational materials. Sensitivity analyses by study quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analyses with all included studies (online suppl. material B Table B1). Subgroup analyses by study design, WHO region, level of care , duration of program, and type of healthcare provider revealed very heterogeneous results for knowledge- and skill-based outcomes (see online suppl. material B Table B1 for results of all remaining subgroup analyses) for which no conclusions could be drawn. The test for subgroup differences by standardization and simulation did not reach statistical significance. Perinatal and Newborn Outcomes Findings were discordant across newborn outcomes. For example, post-NRTP revealed a borderline reduction in risk ( p = 0.05) for stillbirths when compared to pre-NRTP. However, when disaggregated by fresh or macerated stillbirths, there was a 33% (95% CI: 4–68%) increased risk for macerated stillbirths, while fresh stillbirths had no significant risk reduction following the NRTP. This could represent improved reporting and disaggregation of stillbirths. NRTP led to a significant reduction in perinatal mortality (RR = 68%, 95% CI: 52–88%), but no impact on all-cause mortality, mortality due to asphyxia or neonates successfully resuscitated. However, when disaggregated by time, a significant risk reduction was found for very early perinatal mortality (RR = 59%, 95% CI: 46–76%) and very early neonatal mortality (RR = 62%, 95% CI: 46–83%) for post-NRTP compared to pre-training . Due to the number of forest plots, only those with robust mortality outcomes (i.e., with a substantial number of participants) can be found in online supplementary material H. Sensitivity analyses by quality assessment revealed a 31% (95% CI: 5–50%) reduction in stillbirths, while revealing a nonsignificant effect estimates for macerated stillbirths. All other newborn outcomes had effect estimates with similar significance and effect direction compared to analyses with all included studies (i.e., all pooled studies with no sensitivity analysis) (online suppl. material B Table B1). Subgroup analyses by study design, WHO region, level of care , duration of program, and type of healthcare provider varied widely by subgroup (see online suppl. material B Table B1 for results of all remaining subgroup analyses) for which no conclusions could be drawn. The test for subgroup differences by standardization did not reach statistical significance. Comparison 2: Any NR Training Program Intervention versus Control without NR Training Program When comparing intervention-control data, the intervention group which underwent any NRTP had improved mean knowledge test scores and self-efficacy compared to control. Further, the intervention group had a 75% (95% CI: 41–89%) reduced risk for mortality due to asphyxia and a 42% (95% CI: 15–61%) reduced risk of all-cause neonatal mortality, when compared to control (see ). No sensitivity analysis by quality assessment was possible for any NRTP versus no NRTP with intervention and control data. This is because all included studies were either low risk and included in the analysis or high risk, and therefore no studies would have been included in the analysis. The test for subgroup differences by study design, WHO region, duration of program, type of healthcare provider and standardization did not reach statistical significance (online suppl. material B Table B1). Comparison 3: Post-HBB Training versus Pre-HBB Training Knowledge- and Skill-Based Outcomes When looking specifically at HBB training, post-HBB training was associated with improved mean knowledge test scores, and more healthcare providers passed knowledge tests with a score of 75% or higher compared to pre-training. Further, skill-based outcomes (i.e., mean composite practical skills, bag-mask ventilation skills, OSCE A, and OSCE B skills) also improved post-HBB training compared to pre-training . Sensitivity analyses by quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analyses including all studies. The test for subgroup differences by study design did not reach statistical significance for any knowledge- or skill-based outcomes, while subgroups by WHO region and duration of program were significant for some knowledge and skill outcomes but had no impact on others (online suppl. material B Table B2). Although the test for subgroup differences by type of healthcare provider was significant across all knowledge and skill-based outcomes, the impact varied by outcome for which type of provider led to the greatest improvements (online suppl. material B Table B2). Perinatal and Newborn Outcomes Results for post versus pre-HBB training, for the most part, remain the same as for comparison 1 looking at any NRTP given only two studies compared pre-post data for non-HBB interventions on newborn outcomes, while the remaining were all HBB studies. We report here a difference in results for newborn outcomes after removing the non-HBB studies, where post-HBB training reduced the risk of fresh stillbirths (RR = 75%, 95% CI: 64–87%), perinatal mortality (RR = 77%, 95% CI: 55–108%), and very early perinatal mortality (RR = 57%, 95% CI: 40–83%) when compared to pre-HBB training . See online supplementary material H for forest plots on all robust mortality outcomes. Sensitivity analyses revealed a significant reduction in stillbirths (RR = 66%, 95% CI: 48–92%) and significant improvement in neonates successfully resuscitated (RR = 1.76%, 95% CI: 0.74–4.20%) while revealing non-significant effect estimates for fresh stillbirths, macerated stillbirths, and very early perinatal mortality. All other newborn outcomes had effect estimates with similar significance and effect direction when compared to analysis with all included studies (i.e., all pooled studies with no sensitivity analysis). Again, most findings from subgroup analyses (i.e., WHO region, level of care, duration of program, and type of healthcare provider) varied widely by subgroup and thus did not allow for robust conclusions (online suppl. material B Table B2). Studies with randomized intervention-control data for newborn and healthcare provider outcomes on HBB training versus control could not be pooled due to insufficient number of studies . Comparison 4: Post-NRP Training versus Pre-NRP Training Knowledge- and Skill-Based Outcomes Post-NRP training significantly improved mean knowledge and practical composite skills compared to pre-NRP training. Consistent with other training programs, healthcare providers had a higher mean practical composite skill score immediately after training compared to 6 months later . Sensitivity analyses by quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analysis with all included studies. Subgroup analyses by WHO region, level of implementation of care , duration of the program, and type of healthcare provider varied widely across subgroups; therefore, no conclusions could be drawn (see online suppl. material B Table B3). The test for subgroup differences by study design did not reach statistical significance. No studies compared NRP training with pre-post data on perinatal or newborn outcomes. Comparison 5: Any NRP Training Intervention versus Control without Specific NRP Training Pooled analyses, comparing NRP training as the intervention group versus a control group with no NRP training (presumably existing stands of care), revealed improved mean self-efficacy scores for those who underwent training . No sensitivity analysis by the quality of study was possible for intervention and control data. The test for subgroup differences by level of care , WHO region, duration of program, and type of healthcare provider did not reach statistical significance (online suppl. material B Table B3). Additional Comparisons See online supplementary material I for a summary analysis of additional comparisons. 

Knowledge and Skill-Based Outcomes Post-NRTP, participants experienced improvements in mean knowledge test scores, more healthcare providers passed knowledge tests with a score of 75% or higher, and improved self-efficacy compared to pre-NRTP training. However, healthcare providers had borderline significantly higher mean knowledge post-test scores immediately following NR training compared to 3 months later ( p = 0.05). Further, NRTPs also improved both mean composite practical skills and specialized skills (i.e., bag-mask ventilation skills, objective structured clinical examination (OSCE) A and OSCE B skills); however, providers had significantly lower practical skill scores 3- and 6-months later compared to immediately after training . OSCE A and B refer to validated knowledge check questions and simulation tests available in NRTP educational materials. Sensitivity analyses by study quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analyses with all included studies (online suppl. material B Table B1). Subgroup analyses by study design, WHO region, level of care , duration of program, and type of healthcare provider revealed very heterogeneous results for knowledge- and skill-based outcomes (see online suppl. material B Table B1 for results of all remaining subgroup analyses) for which no conclusions could be drawn. The test for subgroup differences by standardization and simulation did not reach statistical significance. Perinatal and Newborn Outcomes Findings were discordant across newborn outcomes. For example, post-NRTP revealed a borderline reduction in risk ( p = 0.05) for stillbirths when compared to pre-NRTP. However, when disaggregated by fresh or macerated stillbirths, there was a 33% (95% CI: 4–68%) increased risk for macerated stillbirths, while fresh stillbirths had no significant risk reduction following the NRTP. This could represent improved reporting and disaggregation of stillbirths. NRTP led to a significant reduction in perinatal mortality (RR = 68%, 95% CI: 52–88%), but no impact on all-cause mortality, mortality due to asphyxia or neonates successfully resuscitated. However, when disaggregated by time, a significant risk reduction was found for very early perinatal mortality (RR = 59%, 95% CI: 46–76%) and very early neonatal mortality (RR = 62%, 95% CI: 46–83%) for post-NRTP compared to pre-training . Due to the number of forest plots, only those with robust mortality outcomes (i.e., with a substantial number of participants) can be found in online supplementary material H. Sensitivity analyses by quality assessment revealed a 31% (95% CI: 5–50%) reduction in stillbirths, while revealing a nonsignificant effect estimates for macerated stillbirths. All other newborn outcomes had effect estimates with similar significance and effect direction compared to analyses with all included studies (i.e., all pooled studies with no sensitivity analysis) (online suppl. material B Table B1). Subgroup analyses by study design, WHO region, level of care , duration of program, and type of healthcare provider varied widely by subgroup (see online suppl. material B Table B1 for results of all remaining subgroup analyses) for which no conclusions could be drawn. The test for subgroup differences by standardization did not reach statistical significance. 

Post-NRTP, participants experienced improvements in mean knowledge test scores, more healthcare providers passed knowledge tests with a score of 75% or higher, and improved self-efficacy compared to pre-NRTP training. However, healthcare providers had borderline significantly higher mean knowledge post-test scores immediately following NR training compared to 3 months later ( p = 0.05). Further, NRTPs also improved both mean composite practical skills and specialized skills (i.e., bag-mask ventilation skills, objective structured clinical examination (OSCE) A and OSCE B skills); however, providers had significantly lower practical skill scores 3- and 6-months later compared to immediately after training . OSCE A and B refer to validated knowledge check questions and simulation tests available in NRTP educational materials. Sensitivity analyses by study quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analyses with all included studies (online suppl. material B Table B1). Subgroup analyses by study design, WHO region, level of care , duration of program, and type of healthcare provider revealed very heterogeneous results for knowledge- and skill-based outcomes (see online suppl. material B Table B1 for results of all remaining subgroup analyses) for which no conclusions could be drawn. The test for subgroup differences by standardization and simulation did not reach statistical significance. 

Findings were discordant across newborn outcomes. For example, post-NRTP revealed a borderline reduction in risk ( p = 0.05) for stillbirths when compared to pre-NRTP. However, when disaggregated by fresh or macerated stillbirths, there was a 33% (95% CI: 4–68%) increased risk for macerated stillbirths, while fresh stillbirths had no significant risk reduction following the NRTP. This could represent improved reporting and disaggregation of stillbirths. NRTP led to a significant reduction in perinatal mortality (RR = 68%, 95% CI: 52–88%), but no impact on all-cause mortality, mortality due to asphyxia or neonates successfully resuscitated. However, when disaggregated by time, a significant risk reduction was found for very early perinatal mortality (RR = 59%, 95% CI: 46–76%) and very early neonatal mortality (RR = 62%, 95% CI: 46–83%) for post-NRTP compared to pre-training . Due to the number of forest plots, only those with robust mortality outcomes (i.e., with a substantial number of participants) can be found in online supplementary material H. Sensitivity analyses by quality assessment revealed a 31% (95% CI: 5–50%) reduction in stillbirths, while revealing a nonsignificant effect estimates for macerated stillbirths. All other newborn outcomes had effect estimates with similar significance and effect direction compared to analyses with all included studies (i.e., all pooled studies with no sensitivity analysis) (online suppl. material B Table B1). Subgroup analyses by study design, WHO region, level of care , duration of program, and type of healthcare provider varied widely by subgroup (see online suppl. material B Table B1 for results of all remaining subgroup analyses) for which no conclusions could be drawn. The test for subgroup differences by standardization did not reach statistical significance. 

When comparing intervention-control data, the intervention group which underwent any NRTP had improved mean knowledge test scores and self-efficacy compared to control. Further, the intervention group had a 75% (95% CI: 41–89%) reduced risk for mortality due to asphyxia and a 42% (95% CI: 15–61%) reduced risk of all-cause neonatal mortality, when compared to control (see ). No sensitivity analysis by quality assessment was possible for any NRTP versus no NRTP with intervention and control data. This is because all included studies were either low risk and included in the analysis or high risk, and therefore no studies would have been included in the analysis. The test for subgroup differences by study design, WHO region, duration of program, type of healthcare provider and standardization did not reach statistical significance (online suppl. material B Table B1). 

Knowledge- and Skill-Based Outcomes When looking specifically at HBB training, post-HBB training was associated with improved mean knowledge test scores, and more healthcare providers passed knowledge tests with a score of 75% or higher compared to pre-training. Further, skill-based outcomes (i.e., mean composite practical skills, bag-mask ventilation skills, OSCE A, and OSCE B skills) also improved post-HBB training compared to pre-training . Sensitivity analyses by quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analyses including all studies. The test for subgroup differences by study design did not reach statistical significance for any knowledge- or skill-based outcomes, while subgroups by WHO region and duration of program were significant for some knowledge and skill outcomes but had no impact on others (online suppl. material B Table B2). Although the test for subgroup differences by type of healthcare provider was significant across all knowledge and skill-based outcomes, the impact varied by outcome for which type of provider led to the greatest improvements (online suppl. material B Table B2). Perinatal and Newborn Outcomes Results for post versus pre-HBB training, for the most part, remain the same as for comparison 1 looking at any NRTP given only two studies compared pre-post data for non-HBB interventions on newborn outcomes, while the remaining were all HBB studies. We report here a difference in results for newborn outcomes after removing the non-HBB studies, where post-HBB training reduced the risk of fresh stillbirths (RR = 75%, 95% CI: 64–87%), perinatal mortality (RR = 77%, 95% CI: 55–108%), and very early perinatal mortality (RR = 57%, 95% CI: 40–83%) when compared to pre-HBB training . See online supplementary material H for forest plots on all robust mortality outcomes. Sensitivity analyses revealed a significant reduction in stillbirths (RR = 66%, 95% CI: 48–92%) and significant improvement in neonates successfully resuscitated (RR = 1.76%, 95% CI: 0.74–4.20%) while revealing non-significant effect estimates for fresh stillbirths, macerated stillbirths, and very early perinatal mortality. All other newborn outcomes had effect estimates with similar significance and effect direction when compared to analysis with all included studies (i.e., all pooled studies with no sensitivity analysis). Again, most findings from subgroup analyses (i.e., WHO region, level of care, duration of program, and type of healthcare provider) varied widely by subgroup and thus did not allow for robust conclusions (online suppl. material B Table B2). Studies with randomized intervention-control data for newborn and healthcare provider outcomes on HBB training versus control could not be pooled due to insufficient number of studies . 

When looking specifically at HBB training, post-HBB training was associated with improved mean knowledge test scores, and more healthcare providers passed knowledge tests with a score of 75% or higher compared to pre-training. Further, skill-based outcomes (i.e., mean composite practical skills, bag-mask ventilation skills, OSCE A, and OSCE B skills) also improved post-HBB training compared to pre-training . Sensitivity analyses by quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analyses including all studies. The test for subgroup differences by study design did not reach statistical significance for any knowledge- or skill-based outcomes, while subgroups by WHO region and duration of program were significant for some knowledge and skill outcomes but had no impact on others (online suppl. material B Table B2). Although the test for subgroup differences by type of healthcare provider was significant across all knowledge and skill-based outcomes, the impact varied by outcome for which type of provider led to the greatest improvements (online suppl. material B Table B2). 

Results for post versus pre-HBB training, for the most part, remain the same as for comparison 1 looking at any NRTP given only two studies compared pre-post data for non-HBB interventions on newborn outcomes, while the remaining were all HBB studies. We report here a difference in results for newborn outcomes after removing the non-HBB studies, where post-HBB training reduced the risk of fresh stillbirths (RR = 75%, 95% CI: 64–87%), perinatal mortality (RR = 77%, 95% CI: 55–108%), and very early perinatal mortality (RR = 57%, 95% CI: 40–83%) when compared to pre-HBB training . See online supplementary material H for forest plots on all robust mortality outcomes. Sensitivity analyses revealed a significant reduction in stillbirths (RR = 66%, 95% CI: 48–92%) and significant improvement in neonates successfully resuscitated (RR = 1.76%, 95% CI: 0.74–4.20%) while revealing non-significant effect estimates for fresh stillbirths, macerated stillbirths, and very early perinatal mortality. All other newborn outcomes had effect estimates with similar significance and effect direction when compared to analysis with all included studies (i.e., all pooled studies with no sensitivity analysis). Again, most findings from subgroup analyses (i.e., WHO region, level of care, duration of program, and type of healthcare provider) varied widely by subgroup and thus did not allow for robust conclusions (online suppl. material B Table B2). Studies with randomized intervention-control data for newborn and healthcare provider outcomes on HBB training versus control could not be pooled due to insufficient number of studies . 

Knowledge- and Skill-Based Outcomes Post-NRP training significantly improved mean knowledge and practical composite skills compared to pre-NRP training. Consistent with other training programs, healthcare providers had a higher mean practical composite skill score immediately after training compared to 6 months later . Sensitivity analyses by quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analysis with all included studies. Subgroup analyses by WHO region, level of implementation of care , duration of the program, and type of healthcare provider varied widely across subgroups; therefore, no conclusions could be drawn (see online suppl. material B Table B3). The test for subgroup differences by study design did not reach statistical significance. No studies compared NRP training with pre-post data on perinatal or newborn outcomes. 

Post-NRP training significantly improved mean knowledge and practical composite skills compared to pre-NRP training. Consistent with other training programs, healthcare providers had a higher mean practical composite skill score immediately after training compared to 6 months later . Sensitivity analyses by quality assessment revealed no significant changes in effect estimates for knowledge- and skill-based outcomes compared to analysis with all included studies. Subgroup analyses by WHO region, level of implementation of care , duration of the program, and type of healthcare provider varied widely across subgroups; therefore, no conclusions could be drawn (see online suppl. material B Table B3). The test for subgroup differences by study design did not reach statistical significance. No studies compared NRP training with pre-post data on perinatal or newborn outcomes. 

Pooled analyses, comparing NRP training as the intervention group versus a control group with no NRP training (presumably existing stands of care), revealed improved mean self-efficacy scores for those who underwent training . No sensitivity analysis by the quality of study was possible for intervention and control data. The test for subgroup differences by level of care , WHO region, duration of program, and type of healthcare provider did not reach statistical significance (online suppl. material B Table B3). 

See online supplementary material I for a summary analysis of additional comparisons. 

Program Strengths Various programs (i.e., HBB, NRP, Emergency Obstetric and Early Newborn Care (EmONC), and the WHO-adapted Emergency Triage Assessment and Treatment guidelines on newborn resuscitation) found that most healthcare providers reported greater knowledge, skills, and confidence in their practice after NRTP implementation or scale-up , while only healthcare providers who partook in HBB programs reported follow-up visits as being useful refreshers . HBB studies also reported that mentorship and real-time advice played a key role in improving confidence, ultimately allowing providers to improve on-site decision-making skills . In addition to mentorship, HBB studies also found that small group and peer-learning experiences allowed for greater interaction with facilitators who were able to provide genuine feedback and promote a collaborative teaching environment . Providers from HBB studies valued hands-on learning experiences over traditional didactic lectures . This was especially helpful when clean and reusable equipment was readily available to providers, as reported by HBB and NRP studies . One EmONC study also noted that there was a large availability of equipment and supplies in regional hospitals at baseline; however, this improved in lower level health facilities after program implementation . One NRP study found that improving accessibility (i.e., flexible training delivery methods) and incentivizing training (i.e., providing snacks) helped increase attendance . Program Challenges or Barriers HBB studies reported a lack of knowledge and skill retention, especially if providers were moved to a new site or employment opportunity . HBB and NRP trainings were frequently reported as being too short with insufficient time for hands-on practice and knowledge gaps , while one HBB study reported that the training was too long . Additionally, one HBB study reported trainees having inadequate time to read and review materials before the course, especially with the high complexity of content for NRTP . Both HBB and NRP studies reported that programs often had unclear and inconsistent instructions, advocating for standardized and clear language during training instructions . One NRP study also found that due to suboptimal training, equipment was often torn, misplaced, or improperly maintained . Staff shortages  and limited space  prevented providers from adequately practicing NR in HBB and NRP studies. One NRP study found that there was poor collaboration among providers and a lack of incentives to attend meetings and trainings . Lastly, one HBB study noted that older midwives were more resistant to change and overcame this by facilitating separate training sessions dedicated to this group . Cost Analysis One study revealed the total cost of implementing a full HBB program in a rural Tanzanian hospital as 4,431 United States dollars (USD) . The cost for 1-day training was 2,084 USD and 1-day refresher training was 1,515 USD . One-day accommodations were estimated at USD 20 and training material was 812 USD . The cost per life saved was 233 USD, while achieving a 4.21 USD per life year gain . Another study reported on the proportional cost of implementing a large-scale HBB program in Tanzania and found that the highest proportion of cost was from initial training and equipment practices (45.2%) , followed by central program administration (37.2%), and follow-up visits (17.6%) . The estimated cost for NRTP implementation was 600 USD per facility . For all key findings of included scale-up studies, see . Laryngeal Mask Airway The topic of laryngeal mask airway (LMA) versus face mask ventilation (FMV) or endotracheal intubation (ETT) was of interest for the purpose of NR practices. During the initial scoping exercise, we identified and leveraged data from an existing recent, high-quality review . Since this manuscript is focused on the de novo findings of the effectiveness and scale-up of NRTPs, we have reported the study authors’ results in online supplementary material J and further contextualized the findings as a future option in LMICs . 

Various programs (i.e., HBB, NRP, Emergency Obstetric and Early Newborn Care (EmONC), and the WHO-adapted Emergency Triage Assessment and Treatment guidelines on newborn resuscitation) found that most healthcare providers reported greater knowledge, skills, and confidence in their practice after NRTP implementation or scale-up , while only healthcare providers who partook in HBB programs reported follow-up visits as being useful refreshers . HBB studies also reported that mentorship and real-time advice played a key role in improving confidence, ultimately allowing providers to improve on-site decision-making skills . In addition to mentorship, HBB studies also found that small group and peer-learning experiences allowed for greater interaction with facilitators who were able to provide genuine feedback and promote a collaborative teaching environment . Providers from HBB studies valued hands-on learning experiences over traditional didactic lectures . This was especially helpful when clean and reusable equipment was readily available to providers, as reported by HBB and NRP studies . One EmONC study also noted that there was a large availability of equipment and supplies in regional hospitals at baseline; however, this improved in lower level health facilities after program implementation . One NRP study found that improving accessibility (i.e., flexible training delivery methods) and incentivizing training (i.e., providing snacks) helped increase attendance . 

HBB studies reported a lack of knowledge and skill retention, especially if providers were moved to a new site or employment opportunity . HBB and NRP trainings were frequently reported as being too short with insufficient time for hands-on practice and knowledge gaps , while one HBB study reported that the training was too long . Additionally, one HBB study reported trainees having inadequate time to read and review materials before the course, especially with the high complexity of content for NRTP . Both HBB and NRP studies reported that programs often had unclear and inconsistent instructions, advocating for standardized and clear language during training instructions . One NRP study also found that due to suboptimal training, equipment was often torn, misplaced, or improperly maintained . Staff shortages  and limited space  prevented providers from adequately practicing NR in HBB and NRP studies. One NRP study found that there was poor collaboration among providers and a lack of incentives to attend meetings and trainings . Lastly, one HBB study noted that older midwives were more resistant to change and overcame this by facilitating separate training sessions dedicated to this group . 

One study revealed the total cost of implementing a full HBB program in a rural Tanzanian hospital as 4,431 United States dollars (USD) . The cost for 1-day training was 2,084 USD and 1-day refresher training was 1,515 USD . One-day accommodations were estimated at USD 20 and training material was 812 USD . The cost per life saved was 233 USD, while achieving a 4.21 USD per life year gain . Another study reported on the proportional cost of implementing a large-scale HBB program in Tanzania and found that the highest proportion of cost was from initial training and equipment practices (45.2%) , followed by central program administration (37.2%), and follow-up visits (17.6%) . The estimated cost for NRTP implementation was 600 USD per facility . For all key findings of included scale-up studies, see . 

The topic of laryngeal mask airway (LMA) versus face mask ventilation (FMV) or endotracheal intubation (ETT) was of interest for the purpose of NR practices. During the initial scoping exercise, we identified and leveraged data from an existing recent, high-quality review . Since this manuscript is focused on the de novo findings of the effectiveness and scale-up of NRTPs, we have reported the study authors’ results in online supplementary material J and further contextualized the findings as a future option in LMICs . 

To increase knowledge about newborn survival in LMICs, we conducted a de novo systematic review to synthesize the most up-to-date evidence on NR strategies and training. This synthesis includes a review of the effectiveness and scale-up of NRTPs, and the effectiveness of LMA versus FMV or ETT . Findings suggest that the NRP and HBB training programs had a similar impact across all outcomes. Both programs improved knowledge- and skill-based outcomes but had discordant newborn outcomes (e.g., mortality). Implementation of the HBB program showed promising cost-effectiveness in LMIC settings. To scale-up current NRTPs, programs should focus on improving long-term retention outcomes and improving training material accessibility. NRTP effectiveness studies, evaluating both NRP and HBB training programs, reported improved knowledge- and skill-based outcomes immediately post-training, but these results were not maintained at follow-up assessment. These findings align with the literature on retention, where both the NRP and HBB programs show retention is low with declining knowledge and skill post-training over time . This is concerning as healthcare providers, although satisfactory to provide NR immediately post-training, may not qualify as having the minimum knowledge and skill required to perform resuscitation at follow-up. This would suggest that one-off training is not suitable in these settings and training programs should prioritize routine refresher courses instead. Many studies have found that a low-dose high-frequency training program can improve retention of knowledge and skills of healthcare providers . Current recommendations from the NRP 8th Edition suggest implementation of Resuscitation Quality Improvement (RQI) with quarterly low-dose, high-frequency sessions for 10–15 min to maintain and improve resuscitation skills . Further research also suggests a Just-In-Time (JIT) training program which offers on-time training for those required may provide promising simulation-based refresher opportunities compared to scheduled training . Additional research should consider the optimal length and frequency of refresher courses. No consistent differences were observed when considering the knowledge- and skill-based outcomes by level of care, study design, WHO region, simulation, standardization, duration of program, or type of healthcare provider. Moreover, no major differences in effect size were identified for knowledge and skill outcomes post-sensitivity analysis by quality assessment. We found mixed results for NRTPs on the outcomes of newborns. No pre-post pooled estimates, and only two intervention-control studies leading to pooled estimate, evaluated the effectiveness of NRP on newborn outcomes. This is likely because the NRP has previously been validated as effective for reducing the risk of neonatal mortality in the literature , and thus more recent studies have focused on healthcare provider knowledge and skills. Additionally, NRP is less likely to be evaluated in LMICs as the resources required to provide NRP may not be available based on the level of care within the country. Studies evaluating pre-post HBB training programs showed a reduced risk of stillbirth and fresh stillbirth but an increased risk of macerated stillbirth. However, findings from a sensitivity analysis by quality assessment revealed a nonsignificant effect estimate for macerated stillbirths after studies appraised as high risk were removed. While studies including macerated births generally had similar demographic findings between control and intervention periods, additional factors such as antenatal care, enrolling women with higher risk pregnancies in the post-intervention group, or improved classification may have increased the heterogeneity within this outcome . When disaggregating mortality by time, HBB post-training also indicated a reduced risk of very early perinatal mortality and very early neonatal mortality and, a systematic review by Patel et al.  assessing all NRTPs also reported a reduced risk of stillbirths, early neonatal mortality, and perinatal mortality among LMICs. According to the literature, stillbirths as commonly observed within perinatal programs are sometimes misclassified as early neonatal deaths, and perhaps more commonly, asphyxiated newborns are often misclassified as fresh stillbirths post hoc . Misclassification of stillbirths in low-resource settings is common, as infrequent access to heart rate monitors and where signs of life are not rigorously checked often cause misclassification . These findings also lend credibility to considering intrapartum or fresh stillbirths as an extension of early neonatal mortality and resuscitation programs as a strong strategy to reduce both. Moreover, it is important to underscore that the terms fresh and macerated stillbirth are not synonymous with intrapartum stillbirths and could underestimate intrapartum stillbirths; therefore, current recommendations suggest reporting disaggregated data for fresh and macerated stillbirth with a focus on foetal heart rate documentation at admission and beyond . It is also important to capture longer term developmental outcomes as such resuscitation programs are scaled up. Subgroup analyses by study design, WHO region, level of care, duration of program, standardization, and type of healthcare provider tended to reveal discordant results across outcomes considered. To effectively implement and scale-up NR strategies in LMICs, our review suggests improving the frequency of refresher training , implementing dedicated hands-on learning and skill opportunities , updating outdated NRTP protocols , including handouts and large training posters , and improving the availability of equipment in training settings . Studies also suggest training more and healthcare providers diverse in specialization  to help with staff shortages. These recommendations are aimed to address barriers currently identified in training programs such as improving knowledge and skill retention, standardizing training protocols, and increasing training opportunities for healthcare providers in LMICs. These findings are in accordance with Wall et al.  who suggest refresher training should be provided on a standard and frequent basis, as well as the need for available, functioning, and clean equipment to improve training accessibility. These findings align with the WHO Essential Newborn Care Course which emphasizes clinical and ongoing practice, ultimately improving knowledge and skill retention, as well as improving access to materials, which are all important goals of scaling-up a resuscitation program. While comprehensive asphyxia care is vital to newborn care, studies reporting on non-NR specific training programs where the effect of NR training outcomes could not be disaggregated from outcomes associated with broad, integrated packages on maternal and child health, were excluded (online suppl. material K). No studies directly compared NRP to HBB, limiting ability to provide conclusions about which program may be better to implement and scale-up in LMIC settings. However, NRP is generally best applied in facilities with qualified providers and settings with access to specialized equipment, whereas HBB may be implemented in primary care settings . HBB also appears to be cost-effective in low-resource settings, though this evidence originates from a single country in Africa and more research is necessary. Two included studies discussed the implementation and cost-effectiveness of the HBB program in Tanzania. One study reported the total cost of implementing an HBB program in rural Tanzania as 4431 USD , while another study reported implementing HBB at large-scale implementation as 600 USD . Although both studies conclude the HBB program is cost-effective, the discrepancy in costs between the two studies may be attributed to the level of implementation (i.e., one rural hospital vs. several facility-level centres). The cost-effectiveness of the NRP in LMIC settings remains unclear and future research is also warranted. Although publications are forthcoming, the Helping Mothers and Babies Survive (HMBS) program may provide promising training opportunities as they target remote and online training while bringing down associated costs to implement and scale-up resuscitation training programs. Strengths and Limitations Our study has several strengths. First, we conducted a rigorous literature search and performed data extraction and quality assessments independently and in duplicate to reduce human error. Second, our review conducted an extensive list of subgroup analyses to identify consistent themes across healthcare providers and newborn outcomes. Third, our project was largely conceptualized and informed by a technical advisory group (TAG), who provided strategic and expert advice to improve the overall quality of our review. We acknowledge several important limitations of this study. First, our review is limited by the quality of included studies, where studies reported as high risk, serious risk, or poor quality depending on the study design, potentially threaten the internal validity of findings. Second, most outcomes had substantially high heterogeneity between included studies, which may be due to the lack of standardized testing and evaluation approach used across studies. Moreover, since included studies were conducted in settings with diverse resources, modified NRTP protocols, and varied experience among providers on resuscitation practices may have led to the increased heterogeneity across findings. Third, the current meta-analyses consist largely of pre-post studies without concurrent control groups, limiting our ability to measure an effect estimate from resuscitation training alone compared to other changes at health facilities or in communities during the same time. Lastly, since both cost-analysis studies were limited to HBB programs in Tanzania, conclusions on cost-effectiveness lack generalizability to all LMICs and training programs, necessitating further research in this area. 

Our study has several strengths. First, we conducted a rigorous literature search and performed data extraction and quality assessments independently and in duplicate to reduce human error. Second, our review conducted an extensive list of subgroup analyses to identify consistent themes across healthcare providers and newborn outcomes. Third, our project was largely conceptualized and informed by a technical advisory group (TAG), who provided strategic and expert advice to improve the overall quality of our review. We acknowledge several important limitations of this study. First, our review is limited by the quality of included studies, where studies reported as high risk, serious risk, or poor quality depending on the study design, potentially threaten the internal validity of findings. Second, most outcomes had substantially high heterogeneity between included studies, which may be due to the lack of standardized testing and evaluation approach used across studies. Moreover, since included studies were conducted in settings with diverse resources, modified NRTP protocols, and varied experience among providers on resuscitation practices may have led to the increased heterogeneity across findings. Third, the current meta-analyses consist largely of pre-post studies without concurrent control groups, limiting our ability to measure an effect estimate from resuscitation training alone compared to other changes at health facilities or in communities during the same time. Lastly, since both cost-analysis studies were limited to HBB programs in Tanzania, conclusions on cost-effectiveness lack generalizability to all LMICs and training programs, necessitating further research in this area. 

NRTPs, including standard NRP and HBB programs, improved knowledge and skill scores immediately post-training that were retained during longer follow-ups, suggesting the need for refresher courses. Both the NRP and HBB appear to be effective; however, two studies reported that the HBB program was cost-effective in Tanzania, suggesting that the HBB program or elements thereof are low-cost and scalable in LMICs. Future research across diverse settings should evaluate the cost-effectiveness of the NRP. Our review could be improved upon with studies directly comparing HBB to NRP, thereby allowing conclusions about which program is most effective in different contexts. To scale-up NRTPs, programs should focus on increasing the frequency of refresher training and improving training material accessibility. 

We gratefully acknowledge the asphyxia TAG of experts for their contributions to the conceptualization of the study. We also gratefully acknowledge the work of Li Jiang who assisted in creating forests plots by level of care for the review topic LMA versus FMV or ETT. 

An ethics statement is not applicable because this study is based exclusively on published studies. 

The authors have no conflicts of interest to declare. 

This work is supported by funding received from the Bill and Melinda Gates Foundation (#INV-042789). The funders had no role in the conceptualization, analysis or writing of this article. 

L.H. and Z.A.B. conceptualized the study. D.S., R.L.H., and L.H. designed the study and carried out the search and study selection. D.S. and R.L.H. completed data collection and critical appraisal. D.S. and L.H. led data analysis. D.S. completed writing of manuscript with substantial contributions from R.L.H., G.D., L.H., T.V., and Z.A.B. 

