The Golden 28 Days of Child Survival

The first two decades of the 21st century can indisputably be characterized by a global health revolution that has led to massive improvements in health outcomes, particularly in terms of child survival. Indeed, never before in the history of mankind the chances of surviving for any new baby born in this world have been greater, with child mortality becoming anecdotal in many industrialized regions, and the number of child deaths decreasing globally at a fast pace, from over 17 million annual deaths in the 1970s to around 5.9 million in 2015 [1]. Such unprecedented and impressive reductions are the result of many national and international efforts and coinciding circumstances but have surely been catalysed by the establishment, back in the year 2000, of the Millennium Development Goals, a set of laudable aims agreed on by all 191 United Nations countries, designed to combat poverty, hunger, disease, illiteracy, environmental degradation and discrimination against women [2]. Although several countries have succeeded in reducing by at least 2/3rds their child mortality estimates in the period 1990–2015, as stipulated by the Millennium Development Goal 4 (MDG4), global progress has been unequal, and the global target has not been completely achieved [3]. The particular push and drive for child survival provided by the MDGs has now been taken over by the more recent sustainable development goals (SDGs), and in particular by SDG3 [2–4], which specifies an even more ambitious global target, to be achieved by the year 2030, and which should be seen as a new opportunity to save millions of lives. It is however important to highlight that such applauded decreases in child mortality offer significant nuances. From a geographical and socio-economic point of view, and despite the fact that such falls have been confirmed in all areas of the world, reductions have been more modest in low- or middle-income (LMIC) countries and in particular in sub-Saharan Africa (SSA). It is no coincidence that up to 99% of all child deaths are now circumscribed to these settings [5, 6], a strident reminder of the many inequities driving global health. From an age category point of view, neonatal deaths, those defined as occurring within the first 28 days of life, have also decreased, but at a much slower rate, estimated at around 3.1% annually, from the 30 deaths per 1000 live births in 2000 to 19 in 2015 [1, 7]. Thus, neonatal mortality has become an increasing driver of the overall global paediatric mortality, representing an increasing proportion of all annual child deaths (37.4% in 1990 and 45.1% or an equivalent of 2.68 million deaths in 2015 [1]). Decreases in neonatal mortality rates (NMRs) have also shown similar regional variations, with reductions ranging from ∼80% in eastern Asia, or ∼50% in southern Asia (SEA) to ∼40% in SSA in the same period [7]. The highest NMRs are found in SSA [27.7 per 1000 life births (LBs) and in SEA (27.6 per 1000 LBs), multiplying by 10-fold those documented in Europe (2.9 per 1000 LBs) [6, 7]. In the absence of changes in the current declining rates, it will be over a century before a newborn from SSA has the same survival probability as one born in Europe [6]. The first month of life is undeniably the most vulnerable period for the child’s survival. Within these first 4 weeks, the risk is greatest at the very beginning of life, with up to three quarters of all deaths occurring in the first 7 days, and half of those in the first 24 h [1, 7, 8]. Thus, surviving through childbirth and the ‘golden first 28 days’ appears therefore as a key milestone required to thrive and lead a healthy subsequent life. But, what makes the neonatal period such a critical moment? Why should a period accounting for as little as 0.1% of the entire length of an average life (70 years) define more significantly the likelihood of surviving than any other time? There are multiple reasons that can account for this, but most of them are primarily related to the fragility of life in its very beginnings, the failures of the health system to address the specific health problems in this particular period and the great successes achieved in recent years in preventing post-neonatal common causes of death. Further explanations regarding the still unacceptably high mortality rates among young children gravitate around two premises: (i) the vicious circle established between poverty and disease, which appears very challenging to break and is particularly noticeable in this vulnerable period; and (ii) the global disparities existing in terms of the quality of and access to healthcare [9], seriously jeopardized in those regions with less resources. A healthy birth requires a previous healthy intrauterine development [10]. For this, the pregnant mother needs to remain as healthy as possible, and a series of maternal conditions (hypertension, diabetes and malnutrition) with potential implications in the survival of the foetus needs to be proactively controlled during the entire duration of gestation, and the puerperium. In rich countries, this is guaranteed by the constant control of the pregnancy and the implementation of a series of preventive and therapeutic strategies designed to keep the dyad mother–child healthy. Comprehensive antenatal consultations can also detect high risk situations and thus trigger the necessary actions so as to accelerate an agile delivery, should this become necessary. In poorer regions, antenatal consultations are increasing, although coverage rates are still far from reaching the current WHO recommendation of a minimum of four ANC visits [11], and more importantly, the quality and availability of the health care interventions provided remain suboptimal. Similar challenges face the critical moment of childbirth, with coverage rates for deliveries attended by a skilled professional remaining insufficiently high, at a median rate of 65% during the period 2009–2014 [12]. Solving the maternal part of the equation responsible for neonatal outcomes requires starting by ensuring that maternal mortality rates also continue to globally decrease [13], in addition to heavily investing in improving the primary healthcare bottlenecks [14], and progressively implementing and scaling-up strategies that have already shown their cost-effectiveness in other settings of the world, or other innovative measures [14, 15]. This is by no means an easy task, or at least not one with may lead to immediate results. Such challenges are particularly blatant also in the context of stillbirths; the neglected victims of poverty, accounting for almost identical numbers of annual deaths to those occurring among newborns [16]; and whose oblivion is finally starting to be adequately addressed in the global health agenda [5, 17]. From the newborn’s point of view, similar challenges can be expected in LMICs in relation to access to care, or quality of the preventive or therapeutic strategies available in country, leading to worsened health outcomes. However, the demographic explosion currently seen in SSA implies that this continent has become the principal birthplace of the world. Indeed, of the circa 130 million new babies born every year in the world, over 30% are already born in SSA, and this trend is expected to increase, with more than one in three children in the world expected to live in the continent by 2050 [18]. Coverage rates of well-known and effective interventions to improve the care and health of the newborns are still lagging in these settings, providing much room for improvement [6, 12, 17]. A simple but rather paradigmatic example has to do with the coverage of post-natal visits for babies, a clear WHO recommendation [19] that is only followed in a median of 28% of the births, globally [12]. How can you prevent, detect or treat disease, if you are missing nearly three quarters of all your target population? This is, indeed, the most neglected period for the provision of quality care [19]. A more philosophical issue with very significant practical implications also hinders our current understanding on how to count, prevent and treat those conditions prematurely killing newborns, and is linked to our fundamentally limited knowledge of what is really killing them. In addition to those ‘invisible’ deaths [20] occurring at the community level outside the health system, and in the absence of functioning vital registration systems, there is a profound lack of knowledge of the real underlying causes for these deaths. According to the last global estimates in 2015, leading causes of death among newborns included preterm birth complications (15.9%), intrapartum-related events (10.7%), infectious diseases, including sepsis/meningitis, pneumonia and tetanus (10.1%), and congenital disorders (5.1%) [1]. However, models utilized to build estimates for LMIC, where the vast majority of preventable deaths concentrate, have shown many flaws, and discrepancies in cause-attributable disease figures [21] have unraveled the shortfall of current methods, predominantly based on data derived from unreliable or poorly specific sources, including verbal autopsy or clinical records. The paucity of evidence-based data and the obvious limitations of currently used methodologies to infer cause of death (CoD) in resource-constrained settings warrant caution when interpreting current CoD estimates, at least if those are to be used for rational health planning and prioritization decisions [22]. Innovation is key to overcome such limitations. In this respect, more robust methodologies, such as the minimally invasive tissue sampling post-mortem sampling techniques [23], validated against the reference complete pathological autopsy as a reliable CoD investigation tool in all age groups—including newborns and stillbirths [24]—may provide actionable and reliable data, and thus contribute to better characterize mortality in this age group and the necessary measures to specifically address it. Importantly, such methods are currently being implemented in sentinel sites across SSA and Asia, for perinatal and paediatric mortality surveillance through the Child Health and Mortality Prevention Surveillance Network (CHAMPS) [25, 26]. Dissemination on an ongoing basis of the results of this ambitious and long-lasting project could potentially contribute to better neonatal survival practices. Irrespective of the said caveats regarding the precision and robustness of current estimates, it is clear that infectious diseases remain in LMIC significant contributors to neonatal morbidity and mortality. Such perinatal infections often result from the vertical transmission of pathogens from the mother to the child. Importantly, for some of these infections, highly effective preventive or therapeutic strategies are available, and as a result of their implementation, their burden in neonates from industrialized countries has been significantly reduced. As a paradigmatic example, the incidence of Group B Streptococcus (GBS) early-onset neonatal sepsis has dramatically declined after the implementation of test and treat (intrapartum antibiotic prophylaxis programmes) in industrialized countries [27, 28]. Conversely, the elevated incidence and exceedingly high case fatality rates associated to GBS in SSA (22% [27]) are a direct consequence of the failure to implement such screening strategies, on account of the scarcity of laboratory support and the fragility of the health systems [27]. Better screening tools, based on point of care rapid diagnostic tests, are needed to bypass the chronic scarcity of laboratory support in this context. Additionally, ‘vertical vaccination’ strategies [29], using mothers as the natural targets of vaccines to prevent disease in their offspring, and relying on the maternal transfer of antibodies to the newborn, could more effectively and rapidly protect newborns which are at high risk but cannot directly benefit from the standard immunization calendars. This strategy has already been successfully implemented for tetanus and pertussis control and is currently being explored for several other pathogens, including GBS, respiratory syncytial virus, flu and Streptococcus pneumoniae. The specific neonatal mortality SDG target aims to reduce NMRs to a maximum of 12 per 1000 LBs in every country of the world by 2030 [4]. The SDGs offer also an international collaborative platform of international consensus to advance together towards the global achievement of these goals. The wider ambitions of the SDGs in comparison with the MDGs cannot dilute the importance of health and child survival in these new objectives. Importantly, in the absence of an accelerated progress in neonatal mortality, the world will struggle to significantly reduce overall child mortality. Mothers and their neonates need to be placed at the centre of all efforts. Universal coverage of essential interventions has the potential to reduce neonatal deaths by an estimated 71%, benefit women and children after the first month and reduce stillbirths [14]. Particular support, attention and stewardship to LMICs, which have the greatest needs—but also the tiniest resources—will be critical so as to enhance the uptake and scale-up of these interventions, in an equitable manner. If every country achieves the SDG target for neonatal survival by 2030, approximately 5 million neonatal lives will be saved throughout the period 2017–30 [7] and all of the efforts concentrated in helping newborns go through the arid and sinuous ‘golden’ first 28 days of life will have been worthwile.