Born Too Soon: Accelerating actions for prevention and care of 15 million newborns born too soon

The Born Too Soon report, published in 2012, drew global attention to the issue of preterm birth and reported that more than 1 in 10 of the world's babies are born too soon each year, 15 million each year [1]. As part of a series entitled "Born Too Soon" drawing from the report, this final paper summarises the problem, underlining the need for concerted action on both the prevention of preterm birth and care of the premature baby, to ensure every mother and every baby survives [2‐6]. We then highlight evidence-based interventions for preterm birth in the context of the wider health system drawing on the other papers in this supplement, and here we focus on the implications for integrating and scaling up those available interventions in low- and middle-income countries where the coverage of care is lowest and the potential lives saved as a result. We also consider research gaps since advancing the research agenda is a critical need to reduce the global burden of preterm birth, requiring innovations for both prevention and care. Finally we detail the analyses for a mortality reduction target for preterm specific neonatal deaths and outline the specific roles all actors must play in this global effort to reduce preterm birth and care for premature babies, which is a marker of the health and care of women and girls, as well as of progress for child survival and development.

The actions identified aim to support the goals of the Global Strategy for Women's and Children's Health launched by the United Nations (UN) Secretary-General Ban Ki-moon in September 2010 to further advance progress for the Millennium Development Goal 4 for child survival and the Every Woman Every Child movement to mobilise action and resources for these goals [7]. By pooling our efforts with each organisation playing to its strengths, our shared goal, as epitomised in Every Woman Every Child, can be realised -- a day when pregnancies are wanted and safe, women survive, babies everywhere get a healthy start in life, and children thrive.

Addressing the burden of preterm birth has a dual track--prevention and care (Figure 1). Reducing risks before, during, and between pregnancies through preconception and antenatal care packages may help preterm birth prevention [4, 5]. Actions taken during labour and birth, and particularly improved care of the neonate have been shown to have major impact [5, 6]. For example, antenatal corticosteroids administered to a pregnant woman in preterm labour can prevent respiratory distress syndrome in premature babies reducing newborn mortality and morbidity [5]. In addition, many of these interventions, such as obstetric care and antibiotics for prelabour premature rupture of membranes (pPROM), also benefit maternal health and prevent stillbirths [8]. Interventions that have been identified through global reviews of the evidence are summarised elsewhere [4‐6] and shown in Figure 1.

Despite the burden of preterm birth, few effective prevention strategies are available for clinicians, policy-makers and program managers. Multiple studies in high-income contexts have attempted to prevent preterm birth, but have not yet identified high-impact interventions in the preconception and antenatal periods. Many interventions have been evaluated, and some have been identified as beneficial though limited in public health impact, such as therapy with progestational agents, which have only been studied in certain high-risk populations. Preliminary studies of interventions to reduce rates of elective caesarean births or inductions without medical indication before the recommended 39 completed weeks of gestation suggest an impact on prevention of early term deliveries in some high- and middle-income countries [9, 10]. A recent study published in The Lancet examined preterm birth prevention potential in 39 high-income countries and estimated that if five interventions reached high coverage there would only be a 5% relative reduction of preterm birth rate from 9·59% to 9·07% of livebirths by 2015, averting an estimated 58,000 preterm births and saving US$3 billion annually [11]. These five interventions were: smoking cessation (0·01 rate reduction), decreasing multiple embryo transfers during assisted reproductive technologies (0·06), cervical cerclage (0·15), use of progesterone agents (0·01), and reduction of elective labour induction or caesarean delivery without medical indication (0·29). The limited number and effectiveness of available interventions for preterm prevention further underscores this critical major knowledge gap, and makes the case for a strategic and coordinated research effort to advance understanding of causes and mechanisms of preterm birth and identification of innovative solutions.

However, the low- and middle-income countries with the highest burden of preterm births also carry the greatest burden of higher-risk conditions for preterm birth that are preventable or treatable. Interventions such as family planning; prevention and management of sexually transmitted infections (STIs); use of insecticide-treated bednets and intermittent preventive treatment for malaria; identification and treatment of pre-eclampsia, and reduction of physical workload are examples of strategies that could improve birth outcomes in in low- and middle-income settings. Unfortunately, to date, few studies have assessed the impact of these interventions on preterm birth in these countries, particularly with accurate measures of gestational age [12]. The greatest potential for the global prevention of preterm birth, therefore, lies in a comprehensive, strategic, and sufficiently-funded research agenda of the causes of preterm birth and novel strategies for prevention [13]. This should be vigorously pursued.

There are some significant intrapartum interventions that reduce the impact of preterm birth. Antenatal corticosteroid injections given to women in preterm labour are highly effective at preventing respiratory distress syndrome in premature babies and associated mortality and long-term impairment, but remain under-used in many low- and some middle-income countries. There is, thus, a need for delivery research that can help understand context-specific reasons for the continued low coverage in these countries and identify ways to adapt known effective strategies for use in low-resource settings [14]. Tocolytic medicines rarely stop preterm labour, but may help delay labour for hours or days, allowing the baby additional precious time to develop before birth. Of course, any strategies to prolong labour, including delaying caesarean birth, must be evaluated against the potential risk of continued exposure of woman and foetus to sub-optimal conditions that may result in harmful effects. Further research is needed on short and long-term health consequences for mother and baby from efforts to prevent preterm labour [5].

As evidenced by the large survival gap between babies born in high-income countries and those born in low- and middle-income countries, effective interventions exist to reduce death and disability in premature babies, yet this care does not reach the poor and most disadvantaged populations where the burden is highest [6]. There is a "know-do gap", or a gap between what is known to work and what is done in practice. Bridging this gap will be critical for saving premature babies globally, and must be linked to implementation research and context specific adaptation and innovation.

More than 60% of all premature babies are born in South Asia and sub-Saharan Africa which have the highest preterm birth rates [15] and half of births are currently in facilities. Most preterm births occur over 32 weeks of gestation (84%), and deaths in these babies can almost all be prevented and in most cases, intensive care is not needed [6] (Figure 1). It is possible to implement some evidence-based interventions for the care of premature babies at the community level through behaviour change initiatives and women's groups [16], as well as home-visit packages with extra care for premature babies, particularly breastfeeding support and awareness of the importance of seeking care when danger signs occur [17]. In a few countries, case management of neonatal sepsis is being scaled up using community-based health workers [18]. However, the highest impact interventions, notably access to quality intrapartum care and emergency obstetric and newborn care [19], require facility-based services. Antenatal corticosteroids and Kangaroo Mother Care (KMC) are evidence-based interventions that are feasible to scale up in low-resource settings and may serve as entry points for strengthening health systems [20, 21].

There is increasing global consensus around essential reproductive, maternal, newborn and child health (RMNCH) interventions [22, 23], including those to address preterm birth (Figure 2). The goal is to achieve universal, equitable coverage and high quality in all these RMNCH interventions. Newborn babies, and especially premature newborns, are the most sensitive test of health systems function as these babies can die within minutes without the right care. For sustainable effect, interventions to prevent preterm birth in the preconception and antenatal periods and to reduce death and disability in premature babies must be integrated within the existing health system.

The continuum of care is a core organising principle for health systems emphasising linkages between healthcare packages across time and through various service delivery strategies [2]. An effective continuum of care addresses the health needs of the adolescent, woman, mother, newborn and child throughout the life cycle, wherever care is provided, whether it be at the home, primary care level or district and regional hospitals. Integrated service delivery packages of evidence-based interventions within the continuum of care have many advantages: cost-effectiveness is enhanced; available human resources are maximised; and services are more family-friendly, reducing the need for multiple visits [24]. Most importantly, they can help prevent stillbirths, improve prevention and care of premature babies and avert death and disability in women, newborns and children [25‐27].

Interventions with the highest impact on the prevention of preterm birth and care of the premature baby in high-mortality and lower-resource settings can be integrated into these health service delivery packages, which exist in most health systems and involve links with maternal and child health services, as well as immunisation, malaria, HIV/AIDS, nutrition, family planning, and other related programs [22]. A schematic matrix of the basic health packages (Figure 2) outlines these packages spanning the continuum of care and through various service delivery modes within the health system, highlighting the interventions included to address preterm birth. The interventions within each package are based on multiple systematic reviews and are consistent with the Partnership for Maternal, Newborn and Child Health Essential Interventions report [23].

While these packages may exist in nearly all health systems, lower-income countries cannot scale up and implement all the individual RMNCH interventions within all the packages at once [25]. Packages usually are initially comprised of the essential interventions and then increase in complexity over time according to local needs and capacity. For example, the Antenatal Care package may start as the WHO focused four visit package and then later add on diabetes screening and routine ultra-sound as the system capacity and funding increases [26]. The functionality of health systems, such as human resource capacity, health facility infrastructure, supply and demand systems, financial resources, government stewardship, district-level management and use of data, will also determine the coverage, quality and rate of change within the continuum of care [28].

In order for health services to save the maximum number of lives, coverage, quality and equity need to be high; thus ensuring high coverage of care means reaching every woman, mother-to-be, mother, newborn, child and family with targeted interventions. Providing quality care involves doing the right thing at the right time. Providing equitable care means ensuring care for all according to need, rather than income, gender or other social grouping. This holds true for the existing inequalities in care within and across high-income as well as low- and middle-income countries. Previous papers in this supplement have identified gaps in coverage, quality, equity and metrics for care during preconception, pregnancy and care of preterm newborns [4‐6].

Current coverage levels for eight indicators across the continuum of care, chosen by the United Nations Commission on Information and Accountability for Women's and Children's Health, are tracked for the 75 priority Countdown to 2015 countries which collectively account for 90% of maternal, newborn and child deaths [29]. Currently, essential care reaches only half of the people in need (Figure 3), and there is a wide variation in coverage levels among countries, with some countries achieving nearly universal coverage and others reaching less than a quarter of the population. Demand for family planning satisfied and antenatal care coverage, even though feasible through primary care services, still leave out many women, especially the poorest. In addition, quality gaps are a missed opportunity for reaching families; for example, when a midwife is present at birth but is not equipped to prevent post partum haemorrhage or to resuscitate a baby who does not breathe [5, 6]. Substantial progress is still needed for the reduction of maternal and newborn deaths, especially for effective, high quality at the vital contact times (e.g., skilled attendant at birth and postnatal care) [29]. Currently, there are no routine data available for many of the interventions for preterm birth prevention and care.

Greater investment in research and, in particular, into discovery of the many complex and interrelated factors causing preterm birth is needed to strengthen prevention and offers a potential over the longer term for significant reductions in mortality, childhood disability and healthcare expenditure. For care of preterm babies, the emphasis is on rapidly scaling up implementations, so that the maximum number of preterm babies and their mothers benefit. Implementation research is needed to understand the most efficient means of scaling up evidenced based solutions. In this way, hundreds of thousands of lives could be saved with the application of current knowledge.

Preterm birth is not a single condition, but a single outcome (birth before 37 completed weeks) due to multiple causes. Hence, there will not be a single solution, but rather an array of solutions that address the various biological, clinical, behavioural and social risk factors that result in preterm birth. This supplement identifies risks for preterm birth and the solutions needed to reduce those risks across the RMNCH continuum; yet for many of these risks, we do not have effective solutions. Important research priorities have been highlighted [4‐6]. A strategic research approach is needed to understand why babies are born preterm or as stillbirths, how to identify women at risk, to test strategies for prevention and care, and reduce death and disability rates for preterm neonates.

Important research themes can be summarised across the research pipeline of description, discovery, development and delivery science, showing the dual agenda of preventing preterm birth and addressing the care and survival gap for babies born preterm (Table 1) [30]. For the preterm prevention research agenda, the greatest emphasis is on discovery and descriptive research, which is a longer-term investment. For the premature baby care agenda, the greatest emphasis is on development and delivery research, with a shorter timeline to impact at scale.

To understand the impact of evidence-based interventions on deaths due to complications of preterm birth, we considered analyses including historical data from high income countries (Figure 4), recent change in middle income countries (Figures 5 and 6) and a new analysis using lives saved modelling.

The Born Too Soon report initiated a process towards achieving goals for preterm birth prevention and presented a new goal for the reduction of deaths due to complications of preterm birth (Figure 7) [48]. The latter goal was set through consultation by a group of technical experts, and several analyses were undertaken to inform this target, notably (1) projections by country of the deaths due to preterm birth from now until 2025, assuming no change in trends and assuming expected changes in Gross National Income (GNI); (2) reduction in preterm-specific neonatal mortality if the historical trends from the United Kingdom or the United States (Figure 4) were applied or if more rapid recent reductions in middle-income countries were applied (Figures 5 and 6); (3) preterm-specific neonatal mortality reductions predicted based on coverage changes according to the Lives Saved Tool Modelling (Table 2). These analyses used data from UN demographic projections of births [49] and the Child Health Epidemiology Reference Group/World Health Organization neonatal cause of death time series, 2000 to 2010 [50].

Using the results from analyses of the three future scenarios (Figure 8), a target for mortality reduction of preterm births was set and agreed by the technical experts (Figure 7).

Over the last decade, the world has changed. Just as it is no longer acceptable for people with HIV/AIDS to remain untreated because they live in poor countries, it is no longer acceptable for women to die while giving birth. Likewise it should be unacceptable for almost 3 million newborns, to die, including those who are born too soon. Over three-quarters of premature babies who die could be saved if basic care reached them and their mothers. Rapid progress is possible. At the same time, research and innovation for preterm birth prevention is urgent. These actions would reduce disability and chronic disease, improve reproductive and maternal health, and build sustainable health systems. We need more frontline health workers who are skilled and confident in newborn care. We need facilities equipped with life-saving commodities, and girls, and women who are educated, and enabled, can protect their own health, and that of their babies.

The authors declare that they have no conflict of interest

The time of JEL and MVK was funded by a grant from Bill & Melinda Gates Foundation to Save the Children's Saving Newborn Lives programme. The Born Too Soon report was funded by March of Dimes, the Partnership for Maternal, Newborn and Child Health and Save the Children. The Born Too Soon series in Reproductive Health was funded by March of Dimes and Save the Children. Funding from Save the Children is provided by a grant from Bill & Melinda Gates Foundation to Save the Children's Saving Newborn Lives programme.