Born Toon Soon: Preterm birth matters

Urgent action is needed to address preterm birth given that the first country-level estimates show that globally 15 million babies are born too soon and rates are increasing in most countries with reliable time trend data. As the first in a supplement entitled "Born Too Soon", this paper focuses on the global policy context. Preterm birth is critical for progress on Millennium Development Goal 4 (MDG) for child survival by 2015 and beyond, and gives added value to maternal health (MDG 5) investments also linking to non-communicable diseases. For preterm babies who survive, the additional burden of prematurity-related disability may affect families and health systems. Prematurity is an explicit priority in many high-income settings; however, more attention is needed especially in low- and middle-income countries where the invisibility of preterm birth as well as its myths and misconceptions have slowed action on prevention and care. Recent global attention to preterm birth hit a tipping point in 2012, with the May 2 publication of Born Too Soon: The Global Action Report on Preterm Birth and with the 2nd annual World Prematurity Day on November 17 which mobilised the actions of partners in many countries to address preterm birth and newborn health. Interventions to strengthen preterm birth prevention and care span the continuum of care for reproductive, maternal, newborn and child health. Both prevention of preterm birth and implementation of care of premature babies require more research, as well as more policy attention and programmatic investment. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth (ISBN 978 92 4 150343 30). The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format.

than 100 experts representing almost 50 agencies, universities, organization and parent groups came together to produce Born Too Soon: Th e Global Action Report on Preterm Birth [5]. Th e report featured the fi rst ever country-level estimates on preterm birth prevalence developed by the Child Health Epidemiology Reference Group, Th e London School of Hygiene & Tropical Medicine and WHO and published in Th e Lancet [1]. Th ese estimates show that prematurity rates are increasing in almost all countries with reliable time trend data [1].
Th e implications of being born too soon extend beyond the neonatal period throughout the life cycle. Babies who are born before they are physically ready to face the world often require special care and face greater risks of serious health problems, including cerebral palsy, intellectual impairment, chronic lung disease and vision and hearing loss. Th is added dimension of lifelong disability exacts a high toll on individuals born preterm, their families and the communities in which they live [6].
Th ere are two-way linkages between preterm birth, low birthweight and non-communicable diseases (NCDs) such as diabetes and hypertension. Firstly, women with these NCDs have an elevated risk of having a low birthweight baby due to prematurity or other causes, demanding increased attention to maternal health and care, including the antenatal diagnosis and management of NCDs [7]. Premature babies, in turn, are at greater risk of developing NCDs like hypertension and diabetes later in life and, if female, of having a preterm and/or low birthweight baby herself. Th us, prematurity not only aff ects a newborn directly but can also result in a vicious intergenerational cycle of risk [8]. Th e link between prematurity and an increased risk of hypertension, diabetes and other NCDs takes on an added public health importance when the reported increases in the rates of NCDs worldwide are taken into consideration. Currently, nine million people under the age of 60 years die from NCDs per year, accounting for more than 63% of all deaths, with the greatest burden in Africa and other lowincome regions where preterm birth rates are also high [9]. With pregestational diabetes and hypertension reported to increase the risk of having a preterm delivery in the US by 38% and 33%, respectively, it is clear that the problem of preterm birth should be a major concern to policymakers, donor organisations and other stake holders in the NCD as well as RMNCH communities [10].

The Millennium Development Goals and beyond
Th e substantial decline in maternal, newborn and child deaths in high-income countries in the early and middle 20th century was a public health triumph. Much of this decline was due to improvements in socioeconomic, sanitation and educational conditions and in population health, most notably a reduction in malnutrition and infectious diseases [11,12]. Th ese advances in public health also resulted from strengthened political will prompted by public pressure, often by health professionals who demanded attention to and investment in necessary sanitary measures, drugs and technologies [13]. Many low-and middle-income countries are now experiencing a similar "health transition, " defi ned as an "encompassing relationship among demographic, epide miologic and health changes that collectively and independently have an impact on the health of a population, the fi nancing of health care and the development of health systems" [14].
Recent acceleration in mortality reduction for mothers and for children aged between 1 and 59 months has been driven, in part, by the Millennium Development Goal (MDG) framework [15,16]. Established by 189 member states in 2000 with a target date of 2015 [17], the eight interlinking global goals provide benchmarks by which to measure success [18]. As such, they have mobilised common action to accelerate progress for the world's poorest families. Th ese goals put reproductive, maternal, newborn and child health (RMNCH) on the global stage by raising their visibility politically and socially and have helped unite the development community in a common framework for action. Th e need to monitor progress has also led to improved and more frequent use of health metrics and to collaboration and consensus on how to strengthen primary health care systems, from community-based interventions to the fi rst referral-level facility at which emergency obstetric care is available [19]. MDG 4 calls for a reduction in the under-5 mortality rate by two-thirds between 1990 and 2015. MDG 5 has two targets: the fi rst calling for a reduction in the maternal mortality ratio by three-quarters and the second for universal access to reproductive health during the same period. Even with the increased visibility and progress that MDGs 4 and 5 have brought to maternal and child survival, the rate of decline for mortality reduction remains insuffi cient to reach the targets, particularly in sub-Saharan Africa and South Asia ( Figure 1). For example, only 37 countries (out of around 180) are currently on track to achieve the MDG 4 target in 2015, although another 26 are close to the target [15]. One important barrier to progress has been the failure to reduce neonatal deaths and particularly those due to prematurity [20]. Child survival programmes have primarily focused on important causes of death after the fi rst four weeks of life such as pneumonia, diarrhoea, malaria and vaccine-preventable conditions [21], resulting in a significant decline in under-5 mortality rates. While important, the concomitant lack of attention to important causes of neonatal mortality like preterm birth, which is now the single largest cause of neonatal mortality accounting directly for one-third of neonatal deaths, has resulted in neonatal deaths becoming an increasing proportion of under-5 deaths, from 37% in 1990 to 44% in 2012 [22], and demonstrating a slower rate of decline than that for under-5 deaths ( Figure 1) [23,24].
Th e actions presented in Born Too Soon [25], if implemented quickly, will accelerate the reduction of neonatal deaths in the last critical days to the 2015 target and beyond. In addition, they will contribute to improved maternal health and care, thus benefi ting women directly. However, when considered in the full context of public health and development, these actions are importantly linked to all eight MDGs ( Figure 2) and should not be thought of as an isolated program of "prematurity care and prevention. " Th e actions require the engagement of organisations and expertise, not only from across the RMNCH spectrum, but also from non-health sectors such as education and environmental sustainability. In addition, they must be fi rmly embedded within existing frameworks for action and accountability, most notably the Every Woman, Every Child eff ort led by UN Secretary-General Ban Ki-moon ( Figure 3). Such engagement will serve to accelerate progress towards all eight MDGs and have an eff ect beyond improving maternal, newborn and child survival.

Preterm birth matters as a public health problem
Preterm births have been accorded a high public health priority in high-income countries due, in part, to cham pions among medical professionals and the power of aff ected parents. In high-income countries, improved care of the premature baby led to the development of neonatology as a discrete medical sub-specialty and the establishment of neonatal intensive care units [26]. Th e high prevalence and costs of prematurity have captured the attention of policy-makers and have demanded attention in many high-income countries. In the United States, for example, 11.5 out of every 100 babies born in 2012 were premature. While this rate has declined over recent years, it still represents an increase of more than 22% since 1981 [27]. In addition, the annual societal economic cost in 2005 (medical, educational and lost productivity combined) associated with preterm birth in the United States was at least $26.2 billion. During that same year, the average fi rst-year medical costs, including both inpatient and outpatient care, were about 10 times greater for preterm ($32,325) than for term infants ($3,325). Th e average length of stay was nine times as long for a preterm newborn (13 days), compared with a baby born at term (1.5 days) [6]. While health plans paid the majority of total allowed costs, out-of-pocket expenses were substantial and signifi cantly higher for premature and low-birthweight newborns, compared with newborns with uncomplicated births [28].
In low-and middle-income countries, there are common myths and misconceptions that have restricted attention and the implementation of interventions to prevent preterm birth and improve the survival and outcome of premature babies (Figure 4).

Preterm birth attention, action and research at a tipping point
With the establishment of the MDGs and recent global eff orts such as Every Woman, Every Child launched by UN Secretary General in support of the Global Strategy for Women's and Children's Health, there is growing urgency worldwide to improve health across the RMNCH continuum of care. Th ere is also a growing consensus on what needs to be done, as evidenced by essential packages of interventions for preconception, antenatal and postnatal care [29]. However, despite the large burden, availability of cost-eff ective solutions and some increase in program funding, a recent global analysis suggests that newborn survival will remain vulnerable on the global agenda without the high-level engagement of policy-makers, adequate funding and specifi c attention to the problem of preterm birth [30]. Th us, over the past decade, the problem of newborn survival has also begun to receive greater attention globally through an increased volume of publications and meetings. Figure 5 summarises key milestones since 2003 in the movement forward to improve newborn survival.
Th e recent global mobilisation around the issue of preterm birth complements the growing awareness of newborn health and the importance of quality care at the time of birth to protect the lives of both women and children. As an increasing proportion of under-5 deaths globally, newborns and the importance of their survival have demanded greater action and guidance, especially by country governments. Th us, the group of stakeholders behind Born Too Soon came together with countries and other global partners to develop Every Newborn: an action plan to end preventable deaths [31]. A roadmap for change, Every Newborn will take forward the Global Strategy for Women's and Children's Health by identifying actions to improve newborn survival, health and development [31]. Consultation enabling inputs into the action plan is central to the development of Every Newborn. Such consultation allows newborn care to be better integrated into RMNCH investments and into programming in countries where specifi c bottlenecks for highimpact interventions such as essential newborn care, antenatal corticosteroids and Kangaroo Mother Care can be overcome. Th e fi rst Global Newborn Health Conference held in South Africa in April 2013 provided the launch of these consultations and included several sessions relating to preterm birth prevention and care. Th e action plan is expected to be released in May 2014 at the WHO World Health Assembly.

Setting research priorities
Despite the high rate of child death and disability due to prematurity, little is known about how to prevent preterm birth and how best to scale up essential care proven to be practical and aff ordable. It is, thus, critical to harness  It an unprecedented global movement that e and inten and by government , mu e , the private ector and civil to addr the major health chal facing women and children around the world. The ort pu into ac the UN Secretary-Ge Global Strategy for Women's and Children's Health, which pre e a roadmap on how to enhance nancing, n policy and improve e on the ground for the vulnerable women and children.
The Every Woman, Every Child rategy m ed commitme from nearly 300 onal and the UN, nongovernmental n (N , health care profe orga academic t o and the private Over 30 commitme ec y g to preterm birth were added with the launch of the Born Too Soon report [5]. The ent of the Com on In and Accountability for Women' and Children Health ha led to the implementa on of arent mechani to track th commitm including the commitmen made for preterm birth. In addi the UN Commi ion on Life Saving Commo e for Women' and Children' Health include everal high-impact medi and technology to reduce the burden of preterm birth [25]. The Every Newborn plan and e rt will further advance pro for egy by fo ng on newborn health and iden ing for improving the linka between r , maternal and child health [31].

Myth 2: E c ve care of the high-risk mother and premature newborn requires the same costly, high-technology interven ons that are common in highincome countries, but is beyond the na onal health budgets of low-and middle-income countries.
Fact. There exists a range of idence-based w-cost int such as Kangaroo Mother Care and antenata costeroids that if emented immediate and substant reduce premat e ated death and di in high-burden countries [26]. High-income countries such as the United States and the United Kingdom significant redu ons in neonata before the intro of neonata intensi care main through im obstetric care and newborn care in ther car feeding support treatment of infe and basic respirato support [26]. In rce se n immediate and nt progress can be made in pre ng deaths d to co a ons from preterm birth with e en ns and i ed before inte care is [25].

Myth 3: The solu ons to prevent preterm birth are known; all that is needed is the scale up of these solu ons to reach all mothers.
Fact. Li e is known about the causes and mechanisms of preterm birt and these since preterm birth is a me of birth not a ni Once a woman is most of the inter to preterm birth turning an ear preterm birth into a ate preterm birth [7]. More kn edge is needed to address the n and reach a point where more preterm births are pr [25].

Myth 4: Programs' a en on to prematurity will draw funding away from other high-priority RMNCH interven ons.
Fact. Ac n to strengthen n and care of prematurit are both e and b in ncia ed nments and a cascade of bene cia e ects on the hea th of wome mothers and newborns. In the reduce the rate of preterm birth and morta and associated with prematurit [25] hence im the pote for economic Indeed since the preterm bab is the most user of such outcomes are a sensi e indicator of em func n. The Lancet Neonatal i al Series presents the e mates of the cause of four million neonatal deaths and highlights the importance of preterm birth as the leading direct cause and a risk factor for neonatal death [42].

2008/ 2009
The Lancet Series on Preterm Birth in high-income countries released [43]. Global and regional mates of preterm birth released by the WHO Department of Re Health Research (RHR) [40] sugges that approximately 13 million births were born preterm in 2005. The WHO global and regional data are published in the March of Dimes White Paper on Preterm Birth [39]. Media coverage reaches more than 600 million people and triggers a commentary in The Lancet calling for increased n on to the problem of preterm birth [44]. The Global Alliance to Prevent Prematurity and irth (GAPPS) launched [45]. governments, donors and foun s, the UN, non-governmental or (NGOs), health care professional organisations, academic u ons and the private sector [46,47]. It presents a roadmap on how to enhance ncing, strengthen policy and improve service on the ground for the most vulnerable women and children.

The Commission on Inform
and Accountabilit for Women's and Children's Health established to implement transparent mechanisms to track the EWEC commitments, including the commitments made for preterm birth. The UN Commission on Life g Comm for Women's and Children's Health launched as part of the EWEC movement to increase access to life-saving medicines and health supplies for the world's most vulnerable people, including newborns [25].

2012
Born Too Soon: The Global Report on Preterm Birth published docume ng the toll of preterm birth for each country [2,49,50]. The report outlines priority ac on care that could save 750,000 newborn lives annually and accelerate preve of preterm birth. The report involves over 50 led by the March of Dimes, Save the Children, PMNCH and WHO and contains a foreword by Ban Ki-moon [5] -the me the UN's Secretary-General has addressed this issue. Over 30 commitments spec y ng to preterm birth are added with the launch of the Born Too Soon report [5]. The puts into ac n the UN Secretary-General's Global Stra for Women's and Children's Health. The launch of the report in May receives major media coverage, including an on the front page of the New York Times, and other media with an es mated reach of 1 billion, in to 72 million Twi r "impressions," through a coordinated social media approach linking to the news media outreach and CNN advert. Momentum con nued in May 2012 with a breakfast of na ministers of health and senior at the World Health Assembly. The Interna onal n of Gynecology and Obstetrics (FIGO) and the Interna onal Pediatric Asso (IPA) releases a Joint Statement on the and treatment of preterm births in October outlining the role that obstetricians and paediatricians have in the treatment of preterm births [51]. World Prematurity Day 2012 am es awareness about preterm birth, reaching an e d global media audience of more than 1.4 billion, including hundreds of media ar cles, a CNN spot with Celine Dion, Facebook and Tw er ac vity, as well as ac v es in more than 60 countries, many driven by parent groups. As part of the World Prematurity Day ac es, the Government of Uganda announces a new accountability-tracked commitment to EWEC, speci c to preterm birth, including investment in scale up of antenatal costeroids [47]. An analysis of preterm birth preven for 39 high-income countries published in The Lancet, shows that implemen of ve interve of non-medically indicated labour or caesarean delivery, smoking cessa decreasing ple embryo transfers during assisted repr technologies, cervical cerclage, and progesterone supplementa avert 58,000 preterm births per year and save about $3 billion USD annually in the 39 countries by 2015. The paper highlights the need for further research into the causes of preterm birth and es methods for prev of prematurity to accelerate the pote for preven especially in high-income countries [52]. To coincide with World Prematurity Day 2012, an editorial in Repro e Health informs on the recent progress for preterm birth and announces the forthcoming series of papers on Born Too Soon [50].

2013
The Newborn plan conceived in 2013, having passed through mul ple na and regional co will be released at the May 2014 World Health Assembly. The Plan will further advance progress for EWEC and related commissions by focusing spec c en on newborn health and id ng ons for improving the linkages among re maternal and child health [31].
preterm birth have been held to draft a "Solution Pathway, " a comprehensive research agenda to advance preterm birth research across the continuum of discovery, development and delivery science and to improve coordination of research activities. Th e agenda, a summary of which will be published in an upcoming edition of Lancet Global Health, is expected to result in continued momentum and investment in research. Additionally, WHO and Saving Newborn Lives convened over 90 world experts in neonatal and birth outcomes research to prioritise a list of more than 200 "best ideas" to improve birth outcomes and newborn health by 2025. Th e ranked priorities will be published soon and include many related to preterm birth [32].

Preterm birth as a test of the continuum of care
Th e Born Too Soon supplement in Reproductive Health is struc tured to refl ect the continuum of care, a core organiz ing principle for health systems, which emphasises the delivery of health care packages across time and through service delivery levels. An eff ective continuum of care addresses the health needs of the adolescent or woman before, during and after her pregnancy, as well as the care of the newborn and child throughout the life cycle, wherever care is provided [33]. Figure 6 shows the continuum of care by time of care giving, throughout the life cycle, from adolescence into pregnancy and birth and then through the neonatal and post-neonatal periods and childhood; and place of caregiving, that is, households, communities and health facilities [33]. Providing RMNCH services through the continuum of care approach has proven cost-eff ective, and there is evidence that this fi nding holds for the prevention and treatment of prematurity as well [33][34][35][36][37]. Th e papers are presented in order of time of caregiving (preconception, during pregnancy and birth and in the postnatal period for care of the preterm baby) [7,26,38]. In each paper the place of caregiving -at home, at the primary care level and in district and regional hospitals -is discussed. While the causes and multiple events during pregnancy that result in a preterm birth require increasingly vigorous research, there are available interventions which, if scaled up and delivered through integrated packages across the RMNCH continuum of care, would have a major and immediate impact on reducing mortality and disability in premature babies. Th ese same interventions would contribute to a modest reduction in preterm birth rates, helping women and their vulnerable babies to survive and thrive.
Th e supplement emphasizes an action agenda through review of the evidence for these interventions to ensure delivery of the best possible care to all women before, between and during pregnancy; at birth; and to all preterm babies and their mothers and families, wherever they live. In addition, the supplement points to areas of research which require increased attention, funding and collaboration among partners in the governmental, nongovernmental and private sectors.
Finally and importantly, the supplement presents actions that require the continued active engagement of all constituencies [25]. Indeed, it is the partners who contributed to the Born Too Soon report and the many others who have joined since with their diversity of expertise and experience who represent the strength of this process. Th eir contributions will help ensure that the actions in this supplement are acted on, sustained and reach the world's poorest families.

Confl ict of interest
The authors declare no confl ict of interest Additional fi le 1. In line with the journal's open peer review policy, copies of the reviewer reports are included as additional fi le 1.  [33].