Reducing neonatal mortality remains a challenge with an estimated 3.0 million neonatal deaths in 2011, three-quarters of these in sub-Saharan Africa and Southern Asia. The leading causes of neonatal death globally are complications of preterm birth, intrapartum-related causes and infections. While post-neonatal, under-5 deaths fell by 47% between 1990 and 2011, neonatal deaths only fell by 32% and they now account for 43% of all under-5 child deaths. This article reviews the progress in reducing neonatal deaths in high-burden countries and presents an overview of known effective interventions to reduce neonatal mortality and the challenges faced in implementing these in high-burden settings. Effective action is possible to reduce neonatal mortality, but innovative approaches to implementation will be required if these preventable deaths are to be avoided.
La réduction de la mortalité néonatale reste un défi, avec une estimation de 3,0 millions de décès néonatals en 2011, les trois quarts de ceux-ci survenant en Afrique subsaharienne et en Asie du sud. Les principales causes des décès néonataux sont globalement les suivantes: complications des naissances prématurées, causes de l'intrapartum et les infections associées. Alors que les décès post-néonataux, des moins de 5 ans ont diminué de 47% entre 1990 et 2011, les décès néonataux n'ont baissé que de 32% et représentent désormais 43% de tous les décès d'enfants de moins de 5 ans. Cet article passe en revue les progrès réalisés dans la réduction de la mortalité néonatale dans les pays fortement touchés et donne un aperçu des interventions efficaces connues pour réduire la mortalité néonatale et les défis rencontrés dans l'implémentation de celles-ci dans les milieux fortement touchés. Une action efficace pour réduire la mortalité néonatale est possible, mais des approches innovantes pour l'implémentation restent nécessaires si ces décès évitables sont à éviter.
Reducir la mortalidad neonatal continúa siendo un reto con aproximadamente 3.0 millones de muertes neonatales acontecidas en el 2011 y tres cuartas partes de ellas sucediendo en África subsahariana y el sudeste asiático. Las principales causas de muerte neonatal a nivel global son: complicaciones por un nacimiento prematuro, causas relacionadas con el parto e infecciones. Mientras que las muertes post-neonatales de menores de 5 años disminuyeron en un 47% entre 1990 y 2011, las muertes neonatales solo disminuyeron en un 32% y ahora son responsables de un 43% de todas las muertes de menores de 5 años. En este artículo se hace una revisión del progreso en la reducción de las muertes en países con una alta carga y presenta una visión general de las intervenciones efectivas conocidas para reducir la mortalidad neonatal así como de los retos a los que hay que enfrentarse para implementarlos en emplazamientos con una alta incidencia. Las acciones efectivas pueden reducir la mortalidad neonatal, pero se requieren aproximaciones innovadoras a la hora de implementarlas si se quiere evitar estas muertes prevenibles.
Around 135 million babies are liveborn worldwide each year. In 2011, an estimated 3.0 million of these died during the first month of life (UNICEF 2012). The neonatal mortality rate (NMR), defined as the number of deaths in the first 28 completed days of life per 1000 livebirths, varies greatly by geographical region (Figure 1). In 2011, the average NMR in countries in developed regions was 3.7 per 1000 livebirths, while in sub-Saharan Africa and Southern Asia, it is almost 10 times greater (UNICEF 2012) based on methodology by Oestergaard (Oestergaard et al. 2011) (Table 1). These two regions account for 52% of all livebirths, but an estimated 78% of all neonatal deaths, and, overall, 98% of neonatal deaths occur in low- and middle-income countries, with approximately half of these deaths occurring at home.
Table 1. Number of neonatal deaths and rate of progress in reduction in neonatal mortality rate 1990–2011
Although countries with the highest death rates also tend to be those with the fewest data available, estimates of numbers of neonatal deaths by cause are now enabling policy makers, health professionals and researchers to improve targeting of interventions to reduce neonatal mortality in the short, medium and long term (AbouZahr et al. 2007; Hill et al. 2007; Mahapatra et al. 2007; Setel et al. 2007).
When and why do neonatal deaths occur?
At least half of all neonatal deaths occur in the 1st 24 h of life, with only 25% occurring after the first week (Lawn et al. 2005; Belizan et al. 2012). It is worth noting that in addition to these neonatal deaths soon after birth, at least 1.2 million stillbirths occur annually during labour (intrapartum), and a high proportion of the world's 280 000 maternal deaths also occur during or within a few hours of labour (Lawn et al. 2011; World Health Organization 2012). Some of the programmatic solutions to prevent early neonatal deaths could also prevent many intrapartum stillbirths and maternal deaths.
The most recent systematic evaluation of direct causes of neonatal deaths estimated that in 2010, the major causes of neonatal deaths globally were direct complications from preterm birth (35%), intrapartum-related events (often previously referred to as birth asphyxia) (23%), with infections, including sepsis, pneumonia, diarrhoea, meningitis and tetanus, responsible for a combined 27% of neonatal deaths (Liu et al. 2012) (Figure 2). The role of preterm birth is even greater than suggested by this figure because preterm birth is not only a direct cause of death, but also an important contributory factor to deaths due to other causes such that over half of all neonatal deaths globally occur in preterm babies (Belizan et al. 2012). Recent initiatives have therefore sought to highlight the importance of preterm birth and to promote interventions both to prevent preterm birth and to improve the care of the preterm baby (Howson et al. 2012; Global Alliance to Prevent Prematurity and Stillbirth).
While complications of preterm birth, intrapartum-related events and infections are the leading causes of neonatal death globally, the cause distribution of neonatal deaths varies between countries depending on their level of neonatal mortality. In countries with the highest NMRs, around half of all neonatal deaths are due to infections, with most of these deaths preventable or treatable. Countries with lower NMR s typically have higher proportions of neonatal deaths caused by preterm birth complications and congenital anomalies. Understanding the timing and differing causes of neonatal deaths is important to inform programmes and allow appropriate targeting of resources. One example of success in recent years has been the reduction in neonatal deaths due to tetanus, in large part due to the effectiveness of tetanus toxoid immunisation and the tetanus elimination programme (WHO 2000; Liu et al. 2012).
Progress in reducing neonatal mortality
Until relatively recently, a common perception that high-tech neonatal intensive care is needed to tackle the problem of neonatal mortality may have led some low-income countries to focus attention and resources on other causes of child deaths thought to be more amenable to intervention. Thus, public health approaches including preventive measures such as immunisation and simple curative care have received much attention and substantial resources, resulting in major reductions in mortality in children over 1 month of age primarily in deaths due to pneumonia, malaria, diarrhoea and measles. As a result, since the second half of the twentieth century, we have witnessed a remarkable reduction in overall child mortality, with a halving of the risk of death before the age of 5 years, but most of this reduction resulted from lives saved after the first 4 weeks of life.
However, historical data from the United States and United Kingdom show emphatically that neonatal mortality can be reduced without neonatal intensive care. The early 20th century saw a rise of child public health expertise with large improvements in hygienic practices around the time of birth, accompanied by a 25% reduction in NMRs in these countries. Improved individual patient care and supportive management was associated with a further halving of NMR between the 1940s and 1970s. The relatively recent introduction, scale-up and refinement of neonatal intensive care have led to a further reduction in NMR from about 15 to 5 per 1000 since the 1970s (Figure 3). Many middle-income countries are following similar trajectories, for example Sri Lanka and Turkey (Preterm Birth Action Group 2012).
Globally, from 1990 to 2011, mortality in children aged one to 59 months has fallen by 47% (average annual deduction of 2.9%). Progress in reducing neonatal mortality has been slower with an estimated 32% reduction from 32 per 1000 in 1990 to 22 in 2011 per 1000 (average annual reduction of 1.8% a year). Worldwide, neonatal deaths now constitute 43% of all under-5 deaths, and in many regions, apart from sub-Saharan Africa, neonatal deaths constitute at least half of all under-5 child deaths (UNICEF 2012). Moreover, progress in reducing NMR has been slowest in the regions with the highest NMRs. Reductions of over 40% have been estimated for most regions, except in South Asia (32%) and sub-Saharan Africa (24%) (Table 1). Reducing neonatal deaths must become a major public health priority in all regions if Millennium Development Goal 4 (MDG 4), to reduce under-5 mortality by two-thirds between 1990 and 2015, is to be achieved (Lawn et al. 2012b).
In addition to big disparities in neonatal mortality between countries, large differences exist within many countries especially where coverage, quality and access to care vary substantially (Barros et al. 2012). In all regions, mortality rates are highest among the most disadvantaged. Analysis of data by socio-economic or other grouping can be useful in planning of national strategies, especially where substantial differences exist, for example India, China (Lahariya & Paul 2010; Yi et al. 2011).
Tackling the problem
Cheap, effective interventions exist that can reduce neonatal mortality in high-mortality/low-resource settings by targeting the leading causes of neonatal mortality, namely preterm birth, intrapartum-related events and infections. These interventions include those which address both primary prevention of these conditions and improving access to, and effectiveness and quality of, curative treatment for those affected with these conditions (Table 2).
Table 2. Selected low-cost effective interventions to reduce neonatal deaths from the 3 leading causes of neonatal mortality in high-burden countries
Cause of neonatal death Reduction in neonatal mortality (%)
Case management of sepsis with antibiotics (Oral/injectable/full supportive care)
Respiratory support for babies with respiratory distress: Oxygen, Bubble CPAP
Interventions to prevent conditions associated with neonatal mortality
In settings with high neonatal mortality levels, improved public health measures, including those related to hygiene, can play an important part in reducing the number of babies exposed to conditions associated with neonatal mortality, in particular those that are infection related. Tetanus toxoid vaccination is estimated to reduce the risk of neonatal death from neonatal tetanus by 94%, and widespread immunisation initiatives have been very important in the large reduction in mortality from tetanus toxoid in the last 20 years (Blencowe et al. 2010). Simple hygienic practices, such as promotion of hand-washing and clean practices around the time of birth and in the post-natal period, may reduce neonatal mortality from infection by 15–40%. Early and exclusive breastfeeding is also associated with reduced neonatal mortality (Blencowe et al. 2011). But these simple, cost-effective things are done by few people in many settings (Edmond et al. 2006; Mullany et al. 2008; Garcia et al. 2011).
The public health preventive measures above are also applicable at the facility level, especially considering the care of high-risk newborns and the prevention of nosocomial infections in neonatal units. In addition, facility- or community-based health professionals can provide further effective preventive measures. These include access to family planning services, antenatal and childbirth care. Family planning can prevent inter-pregnancy intervals of <18 months to reduce adverse perinatal outcomes including stillbirth, preterm birth, smallness for gestational age and increased risk of neonatal mortality (Conde-Agudelo et al. 2006; Cleland et al. 2012). High-quality antenatal care, preferably commenced in the first trimester, with screening for conditions associated with adverse neonatal outcomes, for example, hypertensive disorders, infections including syphilis, diabetes and multiple pregnancies, can also reduce adverse outcomes (Darmstadt et al. 2005; Victora & Rubens 2010). Currently, even in countries with high coverage, there is substantial variation in the quality of existing antenatal care (Conrad et al. 2012; Requejo et al. 2012). Improved care around the time of birth, including antenatal steroids in threatened preterm labour, antibiotics in premature rupture of membranes, monitoring of labour and ensuring availability of timely, quality emergency obstetric and neonatal care, caesarean section and neonatal resuscitation if required can further reduce neonatal mortality (Cousens et al. 2010; Mwansa-Kambafwile et al. 2010; Lee et al. 2011a,b). Facilities can also play an important role in supporting public health measures in their communities, by setting a good example (e.g. early initiation of breastfeeding and delayed bathing in facilities) and by active involvement in training and support of community health workers and delivery of public health messages.
Improved case management of those with conditions associated with neonatal mortality
Most neonatal deaths worldwide therefore can be prevented without high-tech neonatal intensive care. Improved individual case management and supportive care outside of neonatal intensive care units historically led to large reductions in neonatal mortality (Figure 3). More recently, some countries have reduced their NMRs using this approach (Lawn et al. 2012b). Facilities in middle to high-mortality settings are well placed to benefit from the low-tech solutions and lessons learnt over the last century. These include improved understanding of the physiology of the newborn leading to improved resuscitation, thermal and respiratory care (e.g. oxygen delivery devices, bubble CPAP), antibiotics for case management of sepsis, together with more recent developments from middle- and high-mortality settings, for example Kangaroo Mother Care, and training approaches that can be adapted to local settings, for example Integrated Management of Newborn and Childhood Illness and Essential Newborn Care (World Health Organization 2000) (Table 2). Improvement in the timeliness and quality of care in primary and secondary care facilities is important in ensuring that the maximum benefit is derived from these interventions. Community-based health workers can play an important role in the identification and referral of the sick newborn, and in some settings in the delivery of timely case management, especially in emergency situations such as neonatal resuscitation or where barriers to timely, quality facility care currently exists (Bang et al. 1999; Wall et al. 2009; Zaidi et al. 2012). However, to ensure long-term further improvements in newborn health services to reduce both neonatal mortality and morbidity, these community-based curative approaches should be accompanied by strengthening of all aspects of the health system from the family to the community and through all levels of facility care.
In high-income settings, the development and evolution of neonatal intensive care has been associated with a further reduction in NMRs to <5 per 1000 (Philip 2005; Lawn et al. 2012a). These most recent advances, including availability of improved ventilation techniques, surfactant and regionalisation of neonatal services, have not only reduced neonatal mortality, but also improved the care of survivors, reducing long-term morbidity and impairment in these babies. However, low-tech innovations and widespread coverage of known effective alternative solutions and task shifting may facilitate middle- and low-income countries to further reduce neonatal mortality, while also reducing both short and long-term complications, without over-reliance on these costly technologies.
It has been estimated that 40–70% of neonatal deaths in 75 high-mortality countries could be averted by full coverage with 16 feasible interventions. These and other interventions have been included in the Lives saved Tool (LiST), a freely available software tool for programme planners to evaluate the likely effect of increasing coverage of particular interventions on mortality outcomes, including neonatal mortality (Child Health Epidemiology Reference Group 2010).
But uptake of these low-cost effective interventions has remained low in many settings, and in recent years, research has focused on implementation approaches to improve the use of these measures in both the community and in facilities. Women's groups, training of community- and facility-based health workers, community-based intervention packages, antenatal and post-natal home visits and mass media have all been investigated (Gogia & Sachdev 2010; Osrin & Prost 2010; Schiffman et al. 2010; Gogia et al. 2011; McKenzie & Ellis 2011). A variety of community-based intervention packages have been associated with an average 24% reduction in neonatal mortality, but the effectiveness of these strategies has been variable even under study conditions (Lassi et al. 2010). Many studies from South Asia, in settings with high NMR and poor access to facility-based care, have shown improved care practices and encouraging reductions in mortality with these packages. Two RCTs of women's groups using a participatory action cycle reported mortality reductions of 30 (Manandhar et al. 2004) and 45% (Tripathy et al. 2010), however, a third, albeit with lower coverage, found no effect (Azad et al. 2010). Packages including home visits during pregnancy and in the post-natal period, community mobilisation and group education have been associated with reductions in mortality of up to 54%, (Baqui et al. 2008; Kumar et al. 2008) with a 15% reduction in a large scale-up programme in Pakistan (Bhutta et al. 2011). Training of community health workers and health professionals in the integrated management of neonatal and childhood illness, including promotion of post-natal home visits, women's group meetings, referral of sick newborns, improved supply of drugs and strengthening of supervision in India, reduced neonatal deaths by 20% in home-born infants, but had no effect on those born in facilities (Bhandari et al. 2012). However, in a before-and-after study, training community birth attendants alone in 6 countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan and Zambia) in Essential Newborn Care did not reduce mortality (Carlo et al. 2010). There is a paucity of published data on these approaches from sub-Saharan Africa, and research is currently underway in several countries in the region that is urgently needed to inform policy in the region.
Commodities, including clean birth kits and chlorhexidine, may have a role particularly in settings where neonatal deaths due to infection are high and commodities to facilitate clean care are not widely available (Osrin & Hill 2012; Seward et al. 2012). Poor hygiene around the time of birth has long been recognised as a key risk factor for sepsis, and recent debate has centred on the role of clean birth kits to facilitate clean birth practices, amid concerns from some groups that provision of a home-based commodity may deter from facility birth (Hundley et al. 2012). Evidence that clean birth kits reduce mortality is scarce, although a secondary analysis of nearly 20 000 home births in underserved, rural populations in South Asia reported a reduction of 48% in neonatal mortality associated with clean birth kit use (Seward et al. 2012). Clearer evidence exists with respect to chlorhexidine. Three recent large RCTs in high-mortality, community settings in South Asia have reported reductions in neonatal mortality after topical application to the umbilical stump of 4% chlorhexidine (Mullany et al. 2006; Arifeen et al. 2012; Soofi et al. 2012).
The United Nations'; recently launched commission on improving the accessibility of affordable, effective commodities for women's and child's health included 4 neonatal commodities, one of which was chlorhexidine, the others being injectable antibiotic devices, resuscitation devices and antenatal steroids (United Nations 2012). Initiatives focused on implementation and scale-up of these commodities are ongoing (Little et al. 2011; Althabe et al. 2012; American Academy of Pediatrics 2012).
The most effective solutions to reduce neonatal mortality will vary according to setting and over time. In some areas, for example, for the prevention of preterm birth, there remains an urgent need to identify effective innovations to tackle the problem. The many gaps in service supply and coverage of these solutions will need to be addressed in integrated ways, which are sensitive to the socio-cultural context, which is a critical consideration if demand for and coverage with timely, effective care across the continuum from pre-conception to childhood is to be improved (Kerber et al. 2007).
Policy and funding to reduce neonatal deaths
For high-mortality countries, large reductions in NMR are possible without investment in costly high-tech intensive care. Despite the large burden of deaths around the time of birth and the associated cost to families and nations, newborn health and neonatal mortality have until recently rarely been highlighted in global health policy and research agendas. The past 10 years have seen a large increase in policy attention to these issues. Some of the key factors driving this include the raising of the visibility of neonates as a vulnerable group by quantifying the severity of the burden of the problem, whilst identifying cost-effective interventions within the policy window of the MDGs (Shiffman 2010).
However, although official development assistance (ODA) for maternal, newborn and child health doubled from 2003 to 2008 (Pitt et al. 2010), evidence suggests recent slowdown in the rate of funding increases and overall assistance benefiting newborns exclusively remains low (Hsu et al. 2012; Pitt et al. 2012). In addition, most local Ministries of Health and donors have not yet focused sufficient resources on newborn care within maternal and child health programmes. Scale-up of evidence-based newborn care to achieve substantial reductions in neonatal mortality and morbidity will require a large increase in funding. While it is recognised that in the short-term interventions and packages used will need to be adapted according to context to maximise their effectiveness, ultimately, a strong primary care infrastructure linked with functioning referral facilities will be required (Lawn et al. 2012b).
The way forward
The Millennium Development Goals (MDGs) have provided an important impetus to efforts to reduce child deaths, including neonatal deaths. However, whilst progress has been made in reducing neonatal deaths, neonatal mortality remains a large problem with an estimated 3.0 million babies dying during the first 28 days of life in 2011. Many countries will not achieve MDG4 (to reduce the under-5 child mortality rate by two-thirds between 1990 and 2015) and even for those countries that do achieve MDG 4, maintaining momentum in reducing neonatal and child deaths will be difficult. Our focus in this article has been on those settings with the greatest burden of neonatal deaths: low-income countries, especially in sub-Saharan Africa and South Asia. Experience from high-income settings indicates that NMRs of 15/1000 or less are achievable with simple solutions and in the absence of neonatal intensive care.
Although some regional variation exists in the relative contributions of the different causes of neonatal death, complications of preterm birth, intrapartum events and infections are the most important causes across all regions and these results also lead to considerable morbidity and long-term disability (Mwaniki et al. 2012). Knowledge gaps relating to the safety and effectiveness of some specific interventions remain, and further research into these areas is needed (Table 3). However, most neonatal deaths could be prevented with available, simple, cost-effective solutions. A major challenge remains the implementation of these solutions in differing contexts where in many cases, they do not currently reach the most vulnerable. High priority needs to be given to identifying approaches that overcome existing physical, economic and cultural barriers to care-seeking and provision of timely childbirth and newborn care as a prerequisite to enabling the scale-up of these solutions. This will require close partnership between the research and health policy community, with engagement of front-line workers, mothers and families backed by strong local and national leadership and supported by adequate funding. Effective action is possible in all countries, and large reductions in mortality can be achieved with public health and low-tech, cost-effective interventions.
Table 3. Selected further research questions
a) Knowledge gaps relating to the safety and effectiveness of specific interventions to reduce neonatal mortality in low resource settings including
Simplified antibiotics regimes for treating neonatal infection
Postnatal home visits (optimal timing and content)
Community initiated Kangaroo Mother Care
Head cooling for babies with intrapartum related insults
Nasal CPAP for babies with respiratory distress in settings with no availability of further ventilatory support
Identification of modifiable risk factors for preterm birth in different populations and the most effective strategies to target these?
b) Knowledge gaps relating to achieving scale-up of known effective interventions including
How best to achieve high coverage with known effective interventions to reduce neonatal mortality, especially in resource-poor, high burden settings?
Which interventions can safely be delivered at the community level by which level of health care worker?
What are the most effective ways to promote and maintain improvements in the quality of facility based pregnancy, labour and newborn care?