CCA-13893; No of Pages 5 Clinica Chimica Acta xxx (2015) xxx–xxx
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Neonatal and pediatric healthcare worldwide: A report from UNICEF
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Giacomo Guerrera ⁎
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Press Office UNICEF Italian Nat Com, via Palestro 68, 00185 Roma, Italy
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Article history: Received 11 October 2014 Received in revised form 4 March 2015 Accepted 5 March 2015 Available online xxxx
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Keywords: Under-five mortality rate Neonatal mortality rate Maternal mortality rate Millennium Development Goal 4 (MDG 4) UNICEF's immunization program Laboratory medicine
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The 2013 UNICEF annual report on child mortality concluded that between 1990 and 2013, the annual number of deaths among children under-5 years of age has fallen to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48% reduction from the 12.6 million deaths in 1990 (uncertainty range, 12.4 to 12.9 million). About half of under-5 deaths occur in only five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China. By 2050, close to 40% of all live births will take place in Sub-Saharan Africa and 37% of the world's children under age five will live in the region. Most deaths can be attributable to preventable diseases. Pneumonia, diarrhea and malaria together killed roughly 2.2 million children under age five in 2012, accounting for a third of all under-five deaths. Emerging evidence has shown that children are at greater risk of dying before age five if they are born in rural areas, poor households, or to a mother denied basic education. While under-5 mortality was consistently reduced over the past 20 years, few progresses in reducing neonatal mortality as well as maternal mortality have been done. UNICEF is a leading partner in the Global Alliance for Vaccines and Immunization (GAVI), a far-reaching public–private partnership dedicated to increasing children's access to vaccines in poor countries. Early diagnosis and appropriate low-cost therapy of maternal and neonatal diseases are the challenges of the coming years. Therefore, there is the need to promote new experimental and clinical researches and to translate results in clinical practice. Laboratory medicine is strategic for promoting and validating innovative methods for managing the most important causes of maternal, neonatal and under-5 deaths, as well as to consistently reduce the gap between bench and bedside. This may be achieved by a close cooperation between laboratory medicine and industries for the development of new diagnostic tools, especially low-cost disposables easily usable by everyone, namely mothers, for an earlier and specific therapeutic treatments of such diseases like sepsis and infections. © 2015 Published by Elsevier B.V.
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1. Introduction
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In September 2000, the largest-ever gathering of Heads of State assembled in New York to sign the Millennium Declaration in order to solve unequal global health, poverty, and inequities in development, and to establish a set of interrelated goals and targets. The Declaration was endorsed by 189 countries and a roadmap was set with eight critical development goals to be reached by 2015. Of those eight goals, two of them, Millennium Development Goals (MDG) 4 and 5 targeted a reduction in mortality among children younger than 5 years of age by two thirds and a reduction in maternal mortality by three quarters, respectively. The 2013 UNICEF annual report on child mortality concluded that between 1990 and 2013, the annual number of deaths among children under-5 years of age has fallen to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48% reduction from the 12.6 million deaths in 1990 (uncertainty range, 12.4 to 12.9 million) [1]. This trend was obtained despite an increased number of births in many high-burden countries during the same time period.
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⁎ Tel.: +39 06 47809233, +39 3358103150(Mobile). E-mail addresses: [email protected], [email protected].
The sobering realization is that even in countries that will reach their MDG 4 and 5 targets, many will still have high numbers of deaths, with much scope for improvement. About half of under-5 deaths occur in only five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China. India (22%) and Nigeria (13%) together account for more than a third of all under-5 deaths. The leading causes of death among children under-5 include pneumonia (17% of all under-5 deaths), preterm birth complications (15%), intrapartum-related complications (complications during birth; 10%), diarrhea (9%) and malaria (7%). Globally, about 45% of under-5 deaths are attributable to undernutrition. At the end of 2013, among the 75 so-called Countdown countries that have 98% of all maternal deaths and deaths among children under-5, only 17 were on track to reach the MDG 4 target for child mortality and only 9 were on track to reach the MDG 5 target for maternal mortality. It was estimated that 31 countries will achieve MDG 4, 13 countries will achieve MDG 5, and only 9 countries will achieve both targets [2]. In mid-September 2014, Haidong Wang and colleagues from the Institute of Health Metrics and Evaluation (IHME) published a detailed analysis to assess levels and trends of child mortality by using data from the Global Burden of Diseases, Injuries, and Risk Factors Study
http://dx.doi.org/10.1016/j.cca.2015.03.004 0009-8981/© 2015 Published by Elsevier B.V.
Please cite this article as: Guerrera G, Neonatal and pediatric healthcare worldwide: A report from UNICEF, Clin Chim Acta (2015), http:// dx.doi.org/10.1016/j.cca.2015.03.004
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Table 1 Major causes of under-5 deaths, including neonates, in 75 countries. Based on data from WHO-CHERG joint estimates of child deaths by cause for 2000–2010.
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3. Neonatal mortality
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The first 28 days of life have been identified and named as the neonatal period. It represents the most vulnerable time for a child's survival. Reducing neonatal mortality is increasingly important not only because the proportions of under-5 deaths that occur during the neonatal period is increasing as under-5 mortality declines, but also because the health interventions needed to address the major causes of neonatal deaths generally differ from those needed to address other under-5 deaths. While under-5 mortality reduction has been significant, progress in reducing neonatal mortality has been slower [6]. For the world as a whole, the neonatal mortality rate declined 37%, less than the 47% decline in the under-5 mortality rate. There is a consistent pattern of faster decline in the under-5 mortality rate compared with the neonatal mortality rate across all MDG regions. Because declines in the neonatal mortality rate are slower than those in the mortality rate for older children, the share of neonatal deaths among under-five deaths has increased from about 37% in 1990 to 44% in 2012 (Table 2). This trend is expected to continue as under-5 mortality declines. The world's neonatal mortality rate fell from 33 deaths per 1000 live births in 1990 to 21 in 2012. The global number of neonatal deaths declined from 4.6 million in 1990 to 2.9 million in 2012 (Table 2). In five developing regions more than half of under-5 deaths took place in the neonatal period in 2012. Eastern Asia, for instance, has moved so quickly in cutting under-5 mortality rates overall, that neonatal deaths constituted a 60% share in 2012. The other four regions are Northern Africa, Southern Asia, Western Asia and Latin America and the Caribbean. Sub-Saharan Africa, where about a third of under-5 deaths occurred during the neonatal period, has the highest neonatal mortality rate (32 deaths per 1000 live births in 2012) and accounts for 38% of global neonatal deaths. Together with Oceania, the region has recorded the least improvement over the last two decades. Among countries, the variation in neonatal mortality is substantial, ranging from less than 1 death per 1000 live births in Andorra and Luxembourg to 50 in Sierra Leone. Around two-thirds of neonatal deaths occur in just 10 countries, with India accounting for more than a quarter and Nigeria for a tenth. Although neonatal deaths are often more difficult to prevent, there are countries that have had great success in reducing neonatal mortality. In 1990 Estonia had a neonatal mortality rate above 11 per 1000 live births. By 2012 this had been reduced to 1.6, a decline of 86%. Luxembourg (82%), Maldives (81%), Lithuania (78%), the Czech Republic (76%) and Serbia (76%) also reduced their neonatal mortality rates substantially over this period. Children that die before 28 days of life often suffer from diseases and conditions that are readily preventable or treatable with proven, costeffective interventions. Globally, almost a quarter of neonatal deaths
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MDG 4 calls for reducing the under-5 mortality rate by two thirds between 1990 and 2015. At the end of 2012, the under-5 mortality rate declined 47%, from 90 deaths per 1000 live births in 1990 to 48 in 2012. As a result, the total number of under-five deaths in the world has fallen from 12.6 million in 1990 to 6.6 million in 2012, thanks to more effective and affordable treatments, innovative ways of delivering critical interventions to the poor and excluded, and sustained political commitment [4]. Under5 deaths are now concentrated in sub-Saharan Africa (3.37 million) and South Asia (2.34 million), corresponding to 83% of total under-5 deaths. Sub-Saharan Africa continues to confront significant challenges, as the region with the highest mortality rates in the world (98 deaths per 1000 live births in 2012). One in 9 children in sub-Saharan Africa dies before the age of 5; the comparable figure for South Asia is 1 in 16. By 2050, close to 40% of all live births will take place in Sub-Saharan Africa and 37% of the world's children under age five will live in the region. Therefore, the number of under-5 deaths may stagnate or even increase without more progress in the region. Southern Asia also continues to have both a high rate of under-5 mortality (58 deaths per 1000 live births) and a large number of total deaths, at 2.1 million. India has the highest number of under-5 deaths in the world, with 1.4 million under-5 deaths in 2012. All 16 countries with an under-5 mortality rate above 100 deaths per 1000 live births are in Sub-Sahara Africa. The commonest causes of death among children under-5 are shown in Table 1; notably, pneumonia remains the largest single cause of death. Many countries have made and are still making tremendous progress in lowering under-5 mortality. Of the 61 high-mortality countries with at least 40 deaths per 1000 live births in 2012, 25 have reduced their under-5 mortality rate by at least half between 1990 and 2012. Of them, Bangladesh (72%), Malawi (71%), Nepal (71%), Liberia (70%), Tanzania (68%), Timor-Leste (67%), and Ethiopia (67%) have already
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reduced the under-5 mortality rate by two-thirds. In absolute terms, 15 countries made reductions surpassing 100 deaths per 1000 live births since 1990. However, improving child survival remains unfinished, and wide disparities exist among regions and countries [5]. To achieve MDG 4 on time, the global annual rate of reduction in under-5 mortality rate would need to rise to 15.6% for 2012–2015, much faster than the 3.9% achieved over 2005–2012. The rate of decline in under-5 mortality remains insufficient to reach MDG 4, particularly in Sub-Saharan Africa, Oceania, Caucasus and Central Asia, and Southern Asia. If current trends continue, only four MDG regions (Eastern Asia, Northern Africa, Latin America and the Caribbean, and Western Asia) are expected to achieve MDG 4 by 2015. In other words, only 13 of the 61 countries with high under-5 mortality rates (at least 40 deaths per 1000 live births in 2012) are currently on track to achieve MDG 4 with an average annual rate of reduction of 4.4% or more. In 19 countries, and in some instances because of demographic change, the total number of under-5 deaths was found to be actually static or rising, despite falls in mortality rate. If we value the life of every child, as the global community says that it does, the toxic interaction between demographic change and child mortality should be a cause for extreme concern and concerted action.
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2013 (GBD 2013) [3]. Child mortality was estimated in four age groups for 188 countries from 1970 to 2013. Age groups were: early neonatal (0–6 days), late neonatal (7–28 days), postneonatal (29–354 days), and childhood (1–4 years); overall child mortality was estimated as under5 (0–4 years). Despite a 64% reduction from 17.6 million deaths in children under-5 in 1970, in 2013 it was estimated that about 6.3 million children under-5 died; global mortality rate (deaths per 1000 livebirths) in 2013 was estimated to be 14.0 in early neonatal age, 4.4 in late neonatal, 13.2 in postneonatal, 13.1 in childhood. By comparing 2013 with 1970, mortality rate decreased by 55.4% in early neonatal age, by 73.8% in late neonatal, by 47.8% in postneonatal, and by 53.8% in childhood. Overall under-5 rate mortality in 2013 was 44.0, ranging from 152.5 in Guinea-Bissau to 2.3 in Singapore. 26 countries (7 from Asia, 18 from Africa, and Brazil from South America) accounted for 80% of child deaths worldwide; however, the ten countries with the highest under-5 mortality rate were all in sub-Saharan Africa.
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Decline, %
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The MDG-5 target is to reduce by three-quarters the maternal mortality ratio between 1990 and 2015 and to achieve, by 2015, universal access to reproductive health. MDG-5 is the most off track Millennium Development Goal of all. The failure to make more rapid progress on reducing maternal mortality is the most serious wound on the body of global health. This failure indicates that, whatever the rhetoric of reports and speeches, the international community has failed women, and failed them badly. Many reasons will be given in mitigation. But the underlying cause of failure is that development partners have simply not been sufficiently interested in strengthening the systems of health care that women need during pregnancy and childbirth. Most countries are a considerable distance from reaching zero % unmet need [8]. In 2010, the UN Secretary General launched the campaign “Every Woman Every Child”, with the subsequent creation of the Commission on Information and Accountability for Women's and Children's Health [9]. Maternal death has been recently categorized in nine main causes: maternal hemorrhage, maternal sepsis and other pregnancy-related infections, hypertensive disorders of pregnancy, obstructed labor, abortion, other direct maternal disorders, indirect maternal disorders, HIV, and late maternal deaths. In addition, they were identified four different time windows: deaths occurring antepartum (before onset of labor), deaths occurring intrapartum or during the immediate postpartum period (up to 24 h after delivery), deaths occurring during the subacute and delayed postpartum periods (24 h to 42 days after delivery), and late maternal deaths (43 days to 1 year after delivery) [10].
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5. Child mortality rate in high-income countries
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Over the past decades, child mortality in high-income countries has fallen to very low rates and currently it represents only 8% of the global burden of childhood mortality [11]. However, up to 25% of these deaths could be considered preventable. Rates vary considerably among sex, age, and different countries. A recent report on neonatal mortality in England and Wales demonstrated that the highest rates of child mortality are in infancy, especially those within the first 28 days of life [12]; the most common causes of death are perinatal and congenital diseases. Hypoxic–ischemic injury and congenital malformations, particularly congenital heart defects, are the main causes of death in full-term newborns, accounting for 58% of all neonatal deaths. On the other hand, in preterm babies 21% of deaths is due to malformations; two-thirds of
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all deaths are caused by respiratory disease and intraventricular or periventricular hemorrhage, sometimes closely related with prematurity. The risk of neonatal death from malformation is inversely correlated with the gestational age at birth, being higher in premature babies compared with term babies. In babies born before 32 weeks of gestation, infection, including necrotising enterocolitis, lung disease, and brain damage are very common causes of death. In England between one month and 19 years of age, nearly 80% of annual child deaths (1600) is due to: neurological, respiratory, and cardiovascular disorders; infections; and cancers. These data can be considered comparable with those of other European countries, calling for a substantial improvement of public health measures for the prevention of children's deaths from acquired natural causes. Suggested strategies for the reduction of child mortality can be condensed in three recommendations: (a) to accurately monitor the effectiveness of services delivered across the patient pathway by using a dataset of child mortality indicators; (b) to shift delivery of services from a hospital-centric to a community-centric model of care, being the latter more appropriate for children with life-long chronic disorders, complex disability, and obesity; (c) to reduce inequality by more efficient socioeconomic policies, since they significantly affect child survival and health outcomes [13].
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6. UNICEF's immunization programs
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One child dies every 20 s from a disease preventable by vaccine. An estimated 1.5 million children died in 2011 from vaccine-preventable diseases. Every child deserves vaccination. Nearly one in five infants is still unprotected against killer diseases because she or he has not been immunized. The Convention on the Rights of the Child states that all children must have equal access to adequate healthcare; vaccination is a cornerstone of healthcare. The Global Vaccine Action Plan (GVAP) was endorsed by the 194 Member States of the World Health Organization (WHO) Assembly in May 2012 to achieve the Decade of Vaccines vision by delivering universal access to immunization. Under the GVAP adopted by the World Health Assembly in May 2012, the international community has committed to achieve 90% immunization coverage at the national level by 2020 to all children, regardless of where they are born, who they are or where they live. UNICEF supports national immunization programs in several ways [14]. One critical area is the cold chain and logistics (CCL) system, as vaccines are biological products that must be kept within a narrow temperature range, usually 2–8 degrees Centigrade. The cold chain refers to the storage and transport equipment that enables vaccine to be kept at this temperature from the point of manufacture to the point of use in an immunization session or a clinic. The CCL system includes: (a) a management information system capable of collecting and reporting data; (b) a stock inventory control system to ensure proper management of all supplies; (c) storage and warehousing of adequate capacity and quality to ensure their
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were caused by sepsis and meningitis (12%), pneumonia (10%) or diarrhea (2%). These diseases are highly treatable, provided simple interventions and basic treatment knowledge are available [7]. Another 34% of neonatal deaths, the majority of them preventable, were caused by complications from preterm birth.
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8. Beyond the Millennium Development Goals: post-2015 perspectives
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Within 2015, the period of the Millennium Development Goals (MDGs) will end, and the 189 signatory countries will take stock of what has been achieved. Most countries are not achieving MDGs 4 and 5; nevertheless, progress has accelerated over the past five years, suggesting that further gains are possible with continued, intensified programs. This means that there is the absolute need to promote a new global framework for after 2015, proposing updated versions for MDGs 4 and 5 [17] as well as innovative strategies for reducing malnutrition, the most important factor negatively impacting maternal and child health [18]. Between 1990 and 2013, the annual number of deaths among children younger than 5 years of age has fallen to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48% reduction from the 12.6 million deaths (uncertainty range, 12.4 to 12.9 million). This trend was obtained despite an increased number of births in many high-burden countries during the same time period. The sobering realization is that even in countries that will reach their MDG 4 and 5 targets, many will still have high numbers of deaths, with much scope for improvement. By 2050, 1 in every 3 births will be African. Under-5 deaths will continue to concentrate in Africa. Within countries, those deaths are likely to be concentrated still further among the poorest populations. Accelerating the reduction in under-5 mortality is possible by expanding effective preventive and curative interventions that target the main causes of post-neonatal deaths (pneumonia, diarrhea, malaria and under-nutrition) and the most vulnerable newborn babies and children. The post-2015 agenda should include the urgent need to drastically reduce several conditions currently hampering the improvement in the health and wellbeing of women, adolescent girls and children: stillbirths; unsafe abortions; child marriage; violence against women and girls (i.e., female genital mutilation); rape and violence in conflict situations; gender inequality perpetuated by religious belief. The global community must ensure high quality health care for women and children as a universal right, not a local privilege. Post2015 perspectives should include a new vision on what means health and how to deliver it, moving away from the concept of absence of disease and survival towards the integration of wellbeing, resilience, and capability [19]. Health should become the driver of poverty reduction. To do it, there is the need to invest in prevention, to promote equity by destroying social and cultural barriers, to launch education campaigns and programs for citizens and health care workers, and ultimately to improve environmental conditions (i.e., reducing pollution). Early diagnosis of maternal and neonatal diseases could significantly improve the care of babies and mothers. Therefore, there is the need to promote new experimental and clinical researches in the fields of perinatal medicine as well as in molecular biology [20].
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UNICEF is a leading partner in the Global Alliance for Vaccines and Immunization (GAVI), a far-reaching public–private partnership dedicated to increasing children's access to vaccines in poor countries. GAVI supports the poorest countries of the world to expand access to lifesaving vaccines. The Alliance works to strengthen and expand routine immunization services and support the introduction of new and under-used vaccines, including those that protect against hepatitis B and Hib disease. The ultimate objective: establish immunization programs that will function smoothly year after year as part of solid primary health care systems. Over 370 million children had received GAVIsupported vaccines by the end of 2012. With the additional US $4.3 billion pledged in London in 2011, GAVI has been able to accelerate the roll out of vaccination programs worldwide. For example, by the end of 2012, pneumococcal vaccine had been added to the routine immunization systems of 24 countries (and rotavirus vaccine in 12 countries) [15]. In 2012, Ghana and Tanzania simultaneously launched both vaccines, as the GAVI report says, “establishing Africa's leadership in fighting vaccine-preventable deaths” [16]. A new funding window was also opened to provide access to the HPV vaccine. Over 85% of deaths from cervical cancer occur in low- and middle-income countries. In 2013, the first GAVI-supported HPV vaccines were delivered to Kenya, Ghana, Madagascar, Malawi, Niger, Rwanda, Sierra Leone, Tanzania, and Lao PDR are additional demonstration countries. By 2015, one million girls will have received the HPV vaccine in over 20 countries. By 2020, over 30 million girls in more than 40 countries will have been vaccinated against HPV with GAVI support. With new initiatives launched this year on pneumonia and diarrhea, for example, we see great opportunities for GAVI to integrate more of its work with related projects that will reinforce, support, and sustain its core activities on vaccines. In 2011, the financial replenishment of GAVI gave an additional US $4.3 billion towards vaccine coverage. In 2012, new commitments to
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family planning delivered US $2.6 billion to provide 120 million women with access to modern contraceptives by 2020. And in June, 2013, US $4.15 billion was pledged to save 1.7 million lives from under-nutrition. These annual global campaigns, together with initiatives such as the Commodities Commission, are an important means to bring international attention to specific, and often neglected, dimensions of women's and children's health. They are essential public displays of, and material contributions to, political commitment that bring new resources to bear on achieving MDGs 4 and 5.
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integrity; (d) a distribution/maintenance system for efficient transport to every immunization session; and (e) sufficient number of trained personnel at every level, with adequate supervision. When the Expanded Programme on Immunization (EPI) was launched in 1974, less than 5% of the world's children were immunized during their first year of life against six killer diseases: polio; diphtheria; tuberculosis; pertussis (whooping cough); measles; tetanus. Currently, 83% of the world's children under-1 year of age have received these life-saving vaccinations. Increasing numbers of countries, including low-income countries, are adding new and under-used vaccines, like Hepatitis B, Haemophilus influenzae type b (Hib) and yellow fever vaccine to their routine infant immunization schedules. However, onefifth of the world's children – about 22.4 million infants – are not immunized against these killer diseases. UNICEF is pioneering new technology applications via SMS and smartphones to track immunization and keep children up to date on their vaccine schedules. In countries with low immunization rates like the Republic of Congo, UNICEF and frontline health workers are using SMS to register births, follow young families and report infant vaccinations. To reach unimmunized children in Uganda, mobile phone innovations track vaccine availability, disease outbreaks, immunization coverage and quality of medical services. In conflict situations, UNICEF collaborates with United Nations' partners to negotiate temporary cease-fires and accept ‘Days of Tranquility’ to give health workers access to children for vaccination campaigns. UNICEF also engages with the international and local press to relay information about where vaccinations will take place and to encourage that safe passage agreements be respected. At the end of 2012, UNICEF procured more than 500 million immunization syringes, nearly US $30 million worth of ‘cold chain’ equipment, over 1 billion doses of oral polio vaccines, 161 million doses of measles vaccines, 134 million doses of the pentavalent vaccine, which protects against diphtheria, tetanus, whooping cough, hepatitis and Hib with one jab.
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9. Laboratory medicine as a tool for improving maternal and child 400 survival 401 Prevention and early diagnosis are the keywords for reducing maternal and child mortality rate worldwide. In this respect, laboratory medicine can play a strategic role by promoting new diagnostic tests with high sensitivity and specificity. In addition, to improve human health, scientific discoveries must be translated into practical applications.
Please cite this article as: Guerrera G, Neonatal and pediatric healthcare worldwide: A report from UNICEF, Clin Chim Acta (2015), http:// dx.doi.org/10.1016/j.cca.2015.03.004
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[1] United Nations Inter-agency Group for Child Mortality Estimation. Levels and trends in child mortality: report 2013. New York, USA: UNICEF; 2013. [http://www.unicef. org/media/files/2013_IGME_child_mortality_Report.pdf. Accessed September, 6th, 2014]. [2] Bhutta ZA, Black RE. Global maternal, newborn, and child health — so near and yet so far. N Engl J Med 2013;369:2226–35. [3] Wang H, Liddell CA, Coates MM, et al. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014 [pii: S0140-6736(14)60497-9]. [4] Goli S, Arokiasamy P. Maternal and child mortality indicators across 187 countries of the world: converging or diverging. Glob Public Health 2014;9:342–60. [5] Wardlaw T, You D, Newby H, Anthony D, Chopra M. Child survival: a message of hope but a call for renewed commitment in UNICEF report. Reprod Health 2013;10:64. [6] Cooper PA. The challenge of reducing neonatal mortality in low- and middle-income countries. Pediatrics 2014;133:4–6. [7] Thea D, Qazi S. Neonatal mortality—4 million reasons for progress. Lancet 2008; 371(9628):1893–5. [8] Lozano R, Wang H, Foreman KJ, et al. Progress towards millennium development goals 4 and 5 on maternal and child mortality: an updated systematic analysis. Lancet 2011;378:1139–65. [9] WHO, UNICEF, UN Population Fund, World Bank. Trends in maternal mortality: 1990 to 2010. Available at http://www.unfpa.org/webdav/site/global/shared/documents/ publications/2012/Trends_in_maternal_mortality_A4-1.pdf; 2012. [accessed Jan 31, 2014]. [10] Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, et al. Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384(9947):980–1004. [11] Fraser J, Sidebotham P, Frederick J, Covington T, Mitchell EA. Learning from child death review in the USA, England, Australia, and New Zealand. Lancet 2014; 384(9946):894–903. [12] Sidebotham P, Fraser J, Fleming P, Ward-Platt M, Hain R. Patterns of child death in England and Wales. Lancet 2014;384(9946):904–14. [13] Sidebotham P, Fraser J, Covington T, et al. Understanding why children die in highincome countries. Lancet 2014;384(9946):915–27. [14] Duclos P, Dumolard L, Abeysinghe N, et al. Progress in the establishment and strengthening of national immunization technical advisory groups: analysis from the 2013 WHO/UNICEF joint reporting form, data for 2012. Vaccine 2013;31: 5314–20. [15] [No authors listed]WHO Global rotavirus surveillance network—a strategic review of the first 5 years (2008–2012). EMBO Mol Med 2014;6:708–20. [16] Canavan ME, Sipsma HL, Kassie GM, Bradley EH. Correlates of complete childhood vaccination in East African countries. PLoS ONE 2014;9:e95709. [17] Requejo JH, Bryce J, Barros AJ, et al. Countdown to 2015 and beyond: fulfilling the health agenda for women and children. Lancet 2014 [pii: S0140-6736(14)60925-9]. [18] Requejo JH, Bhutta ZA. The post-2015 agenda: staying the course in maternal and child survival. Arch Dis Child 2015;100(Suppl. 1):S76–81. [19] [No Authors listed]Women, children, and adolescents: the post-2015 agenda. Lancet 2014;384:1159. [20] Souza JP, Widmer M, Gülmezoglu AM, et al. Maternal and perinatal health research priorities beyond 2015: an international survey and prioritization exercise. Reprod Health 2014;11:61. [21] Arbuckle MR, Gordon JA, Pincus HA, Oquendo MA. Bridging the gap: supporting translational research careers through an integrated research track within residency training. Acad Med 2013;88:759–65. [22] Mussap M, Antonucci R, Noto A, Fanos V. The role of metabolomics in neonatal and pediatric laboratory medicine. Clin Chim Acta 2013;426:127–38. [23] Patti GJ, Yanes O, Siuzdak G. Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 2012;13:263–9. [24] Ramautar R, Berger R, van der Greef J, Hankemeier T. Human metabolomics: strategies to understand biology. Curr Opin Chem Biol 2013;17:841–6. [25] Mussap M, Fanos V. Reducing neonatal mortality and expenditure in the era of health care crisis: is it possible? J Matern Fetal Neonatal Med 2012;25(Suppl. 5):1–3. [26] Dessì A, Cesare Marincola F, Masili A, Gazzolo D, Fanos V. Clinical metabolomics and nutrition: the new frontier in neonatology and pediatrics. Biomed Res Int 2014; 2014:981219. [27] UNICEF. Committing to child survival: a promise renewed progress report 2013. New York. http://www.unicef.org/publications/files/APR_Progress_Report_2013_9_ Sept_2013.pdf; 2013. [Accessed September, 6th, 2014].
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A revitalized commitment to child survival towards the ultimate aim of ending preventable child deaths is essential. A Promise Renewed (the call to action spearheaded by UNICEF and the US Agency for International Development to end all preventable child deaths by 2035) is such a commitment and more than 170 countries have signed on to it. Countries, the United Nations and its agencies, civil society and private sector organizations must commit to redouble their efforts to reduce child mortality and include this commitment in the post-2015 agenda. Contrary to popular belief, achieving reductions in maternal, neonatal and child mortality does not require expensive health care. There is evidence to show that significant progress can be made through the delivery of costeffective, proven interventions at the community level. Millions of mothers and children can be saved through essential low cost health care (State of the World’s Mothers 2008) designed based on the realities of the communities where the services are being provided. Investment in front-line health workers and support systems is critical, yet health
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budgets are heavily invested in tertiary care—a level of care that the majority of women and children never reach. Care at birth brings a triple return on investment, saving mothers, newborns and unborn children. Scaling up low-cost solutions to address preterm birth could reduce these deaths by three-quarters, notably with antenatal steroid injections to women in preterm labor and with kangaroo mother care, where the preterm baby is held skin to skin with their mother [27].
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Such discoveries typically begin at “the bench” with basic research and then progress to the clinical level, or the patient’s “bedside.” Again, laboratory medicine is a valuable tool for closing the gap between the bench and the bedside research [21]. The rapid development of methods based on metabolomics studies may be considered a paradigmatic example of how sophisticated research can be translated into clinical practice [22]. Laboratory medicine was based for a long time on the measurement of singles metabolites (substrates, enzymes, proteins, hormones, ions, and various other biochemical substances) representing a source of information related with health and disease. After the publication of the first full genome sequence in the mid-1990s, the rapid development of a new generation of diagnostic tests, including the ability of high throughput ‘omics’ platforms for profiling a large number of analytes in a single array, has radically changed the role of clinical pathologists. This global innovation in laboratory medicine will open new perspectives for reducing the gap between new discoveries from experimental studies into clinically available tests. Among ‘omics’ (genomics, transcriptomics, proteomics, etc.), metabolomics offers several advantages based on the fact that it can be considered the link between genotypes and phenotypes, being metabolites the ultimate response of biological systems either to genetic or environmental changes [23]. A large amount of metabolomics studies from the literature have undeniably demonstrated that changes in the metabolic profile allow: (a) a very early identification of subjects at risk to develop a disease, much earlier than any other laboratory test, even in the fetal life; (b) an accurate recognition of the effectiveness of the therapeutic treatment; (c) to reduce drastically any overlap between subjects with either a disease or at risk to develop a disease with healthy subjects; (d) to accurately predict patients outcome on the basis of differences between metabolic profiles and with a minimal or null rate of false positive and false negative results; (e) implementation of personalized medicine in clinical practice [24]. Metabolomics is opening encouraging expectations for improving the care in the early infancy and in childhood: as reported elsewhere [25], one of the most exciting challenges is the possibility to transform experimental results from metabolomics studies into lowcost devices (e.g., dipsticks) easily usable by anyone (e.g., parents) for the early, accurate identification of severe diseases very common in low-income countries, like sepsis, necrotizing enterocolitis, acute kidney injury, and many other critical clinical conditions. A recent study has demonstrated the importance of metabolomics for investigating the metabolic changes due to malnutrition (insufficient as well as excessive nutrition), both in fetal and post-natal life, including the effects of diet in pediatrics [26]. The definition of the interactions between nutrients and cell metabolites could lead to the ‘personalized nutrition’, tailored to the single genome of each child.
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Contents lists available at ScienceDirect
Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim
Neonatal and pediatric healthcare worldwide: A report from UNICEF
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Giacomo Guerrera ⁎
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Press Office UNICEF Italian Nat Com, via Palestro 68, 00185 Roma, Italy
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Article history: Received 11 October 2014 Received in revised form 4 March 2015 Accepted 5 March 2015 Available online xxxx
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Keywords: Under-five mortality rate Neonatal mortality rate Maternal mortality rate Millennium Development Goal 4 (MDG 4) UNICEF's immunization program Laboratory medicine
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The 2013 UNICEF annual report on child mortality concluded that between 1990 and 2013, the annual number of deaths among children under-5 years of age has fallen to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48% reduction from the 12.6 million deaths in 1990 (uncertainty range, 12.4 to 12.9 million). About half of under-5 deaths occur in only five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China. By 2050, close to 40% of all live births will take place in Sub-Saharan Africa and 37% of the world's children under age five will live in the region. Most deaths can be attributable to preventable diseases. Pneumonia, diarrhea and malaria together killed roughly 2.2 million children under age five in 2012, accounting for a third of all under-five deaths. Emerging evidence has shown that children are at greater risk of dying before age five if they are born in rural areas, poor households, or to a mother denied basic education. While under-5 mortality was consistently reduced over the past 20 years, few progresses in reducing neonatal mortality as well as maternal mortality have been done. UNICEF is a leading partner in the Global Alliance for Vaccines and Immunization (GAVI), a far-reaching public–private partnership dedicated to increasing children's access to vaccines in poor countries. Early diagnosis and appropriate low-cost therapy of maternal and neonatal diseases are the challenges of the coming years. Therefore, there is the need to promote new experimental and clinical researches and to translate results in clinical practice. Laboratory medicine is strategic for promoting and validating innovative methods for managing the most important causes of maternal, neonatal and under-5 deaths, as well as to consistently reduce the gap between bench and bedside. This may be achieved by a close cooperation between laboratory medicine and industries for the development of new diagnostic tools, especially low-cost disposables easily usable by everyone, namely mothers, for an earlier and specific therapeutic treatments of such diseases like sepsis and infections. © 2015 Published by Elsevier B.V.
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1. Introduction
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In September 2000, the largest-ever gathering of Heads of State assembled in New York to sign the Millennium Declaration in order to solve unequal global health, poverty, and inequities in development, and to establish a set of interrelated goals and targets. The Declaration was endorsed by 189 countries and a roadmap was set with eight critical development goals to be reached by 2015. Of those eight goals, two of them, Millennium Development Goals (MDG) 4 and 5 targeted a reduction in mortality among children younger than 5 years of age by two thirds and a reduction in maternal mortality by three quarters, respectively. The 2013 UNICEF annual report on child mortality concluded that between 1990 and 2013, the annual number of deaths among children under-5 years of age has fallen to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48% reduction from the 12.6 million deaths in 1990 (uncertainty range, 12.4 to 12.9 million) [1]. This trend was obtained despite an increased number of births in many high-burden countries during the same time period.
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⁎ Tel.: +39 06 47809233, +39 3358103150(Mobile). E-mail addresses: [email protected], [email protected].
The sobering realization is that even in countries that will reach their MDG 4 and 5 targets, many will still have high numbers of deaths, with much scope for improvement. About half of under-5 deaths occur in only five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China. India (22%) and Nigeria (13%) together account for more than a third of all under-5 deaths. The leading causes of death among children under-5 include pneumonia (17% of all under-5 deaths), preterm birth complications (15%), intrapartum-related complications (complications during birth; 10%), diarrhea (9%) and malaria (7%). Globally, about 45% of under-5 deaths are attributable to undernutrition. At the end of 2013, among the 75 so-called Countdown countries that have 98% of all maternal deaths and deaths among children under-5, only 17 were on track to reach the MDG 4 target for child mortality and only 9 were on track to reach the MDG 5 target for maternal mortality. It was estimated that 31 countries will achieve MDG 4, 13 countries will achieve MDG 5, and only 9 countries will achieve both targets [2]. In mid-September 2014, Haidong Wang and colleagues from the Institute of Health Metrics and Evaluation (IHME) published a detailed analysis to assess levels and trends of child mortality by using data from the Global Burden of Diseases, Injuries, and Risk Factors Study
http://dx.doi.org/10.1016/j.cca.2015.03.004 0009-8981/© 2015 Published by Elsevier B.V.
Please cite this article as: Guerrera G, Neonatal and pediatric healthcare worldwide: A report from UNICEF, Clin Chim Acta (2015), http:// dx.doi.org/10.1016/j.cca.2015.03.004
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Table 1 Major causes of under-5 deaths, including neonates, in 75 countries. Based on data from WHO-CHERG joint estimates of child deaths by cause for 2000–2010.
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3. Neonatal mortality
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The first 28 days of life have been identified and named as the neonatal period. It represents the most vulnerable time for a child's survival. Reducing neonatal mortality is increasingly important not only because the proportions of under-5 deaths that occur during the neonatal period is increasing as under-5 mortality declines, but also because the health interventions needed to address the major causes of neonatal deaths generally differ from those needed to address other under-5 deaths. While under-5 mortality reduction has been significant, progress in reducing neonatal mortality has been slower [6]. For the world as a whole, the neonatal mortality rate declined 37%, less than the 47% decline in the under-5 mortality rate. There is a consistent pattern of faster decline in the under-5 mortality rate compared with the neonatal mortality rate across all MDG regions. Because declines in the neonatal mortality rate are slower than those in the mortality rate for older children, the share of neonatal deaths among under-five deaths has increased from about 37% in 1990 to 44% in 2012 (Table 2). This trend is expected to continue as under-5 mortality declines. The world's neonatal mortality rate fell from 33 deaths per 1000 live births in 1990 to 21 in 2012. The global number of neonatal deaths declined from 4.6 million in 1990 to 2.9 million in 2012 (Table 2). In five developing regions more than half of under-5 deaths took place in the neonatal period in 2012. Eastern Asia, for instance, has moved so quickly in cutting under-5 mortality rates overall, that neonatal deaths constituted a 60% share in 2012. The other four regions are Northern Africa, Southern Asia, Western Asia and Latin America and the Caribbean. Sub-Saharan Africa, where about a third of under-5 deaths occurred during the neonatal period, has the highest neonatal mortality rate (32 deaths per 1000 live births in 2012) and accounts for 38% of global neonatal deaths. Together with Oceania, the region has recorded the least improvement over the last two decades. Among countries, the variation in neonatal mortality is substantial, ranging from less than 1 death per 1000 live births in Andorra and Luxembourg to 50 in Sierra Leone. Around two-thirds of neonatal deaths occur in just 10 countries, with India accounting for more than a quarter and Nigeria for a tenth. Although neonatal deaths are often more difficult to prevent, there are countries that have had great success in reducing neonatal mortality. In 1990 Estonia had a neonatal mortality rate above 11 per 1000 live births. By 2012 this had been reduced to 1.6, a decline of 86%. Luxembourg (82%), Maldives (81%), Lithuania (78%), the Czech Republic (76%) and Serbia (76%) also reduced their neonatal mortality rates substantially over this period. Children that die before 28 days of life often suffer from diseases and conditions that are readily preventable or treatable with proven, costeffective interventions. Globally, almost a quarter of neonatal deaths
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MDG 4 calls for reducing the under-5 mortality rate by two thirds between 1990 and 2015. At the end of 2012, the under-5 mortality rate declined 47%, from 90 deaths per 1000 live births in 1990 to 48 in 2012. As a result, the total number of under-five deaths in the world has fallen from 12.6 million in 1990 to 6.6 million in 2012, thanks to more effective and affordable treatments, innovative ways of delivering critical interventions to the poor and excluded, and sustained political commitment [4]. Under5 deaths are now concentrated in sub-Saharan Africa (3.37 million) and South Asia (2.34 million), corresponding to 83% of total under-5 deaths. Sub-Saharan Africa continues to confront significant challenges, as the region with the highest mortality rates in the world (98 deaths per 1000 live births in 2012). One in 9 children in sub-Saharan Africa dies before the age of 5; the comparable figure for South Asia is 1 in 16. By 2050, close to 40% of all live births will take place in Sub-Saharan Africa and 37% of the world's children under age five will live in the region. Therefore, the number of under-5 deaths may stagnate or even increase without more progress in the region. Southern Asia also continues to have both a high rate of under-5 mortality (58 deaths per 1000 live births) and a large number of total deaths, at 2.1 million. India has the highest number of under-5 deaths in the world, with 1.4 million under-5 deaths in 2012. All 16 countries with an under-5 mortality rate above 100 deaths per 1000 live births are in Sub-Sahara Africa. The commonest causes of death among children under-5 are shown in Table 1; notably, pneumonia remains the largest single cause of death. Many countries have made and are still making tremendous progress in lowering under-5 mortality. Of the 61 high-mortality countries with at least 40 deaths per 1000 live births in 2012, 25 have reduced their under-5 mortality rate by at least half between 1990 and 2012. Of them, Bangladesh (72%), Malawi (71%), Nepal (71%), Liberia (70%), Tanzania (68%), Timor-Leste (67%), and Ethiopia (67%) have already
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reduced the under-5 mortality rate by two-thirds. In absolute terms, 15 countries made reductions surpassing 100 deaths per 1000 live births since 1990. However, improving child survival remains unfinished, and wide disparities exist among regions and countries [5]. To achieve MDG 4 on time, the global annual rate of reduction in under-5 mortality rate would need to rise to 15.6% for 2012–2015, much faster than the 3.9% achieved over 2005–2012. The rate of decline in under-5 mortality remains insufficient to reach MDG 4, particularly in Sub-Saharan Africa, Oceania, Caucasus and Central Asia, and Southern Asia. If current trends continue, only four MDG regions (Eastern Asia, Northern Africa, Latin America and the Caribbean, and Western Asia) are expected to achieve MDG 4 by 2015. In other words, only 13 of the 61 countries with high under-5 mortality rates (at least 40 deaths per 1000 live births in 2012) are currently on track to achieve MDG 4 with an average annual rate of reduction of 4.4% or more. In 19 countries, and in some instances because of demographic change, the total number of under-5 deaths was found to be actually static or rising, despite falls in mortality rate. If we value the life of every child, as the global community says that it does, the toxic interaction between demographic change and child mortality should be a cause for extreme concern and concerted action.
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2013 (GBD 2013) [3]. Child mortality was estimated in four age groups for 188 countries from 1970 to 2013. Age groups were: early neonatal (0–6 days), late neonatal (7–28 days), postneonatal (29–354 days), and childhood (1–4 years); overall child mortality was estimated as under5 (0–4 years). Despite a 64% reduction from 17.6 million deaths in children under-5 in 1970, in 2013 it was estimated that about 6.3 million children under-5 died; global mortality rate (deaths per 1000 livebirths) in 2013 was estimated to be 14.0 in early neonatal age, 4.4 in late neonatal, 13.2 in postneonatal, 13.1 in childhood. By comparing 2013 with 1970, mortality rate decreased by 55.4% in early neonatal age, by 73.8% in late neonatal, by 47.8% in postneonatal, and by 53.8% in childhood. Overall under-5 rate mortality in 2013 was 44.0, ranging from 152.5 in Guinea-Bissau to 2.3 in Singapore. 26 countries (7 from Asia, 18 from Africa, and Brazil from South America) accounted for 80% of child deaths worldwide; however, the ten countries with the highest under-5 mortality rate were all in sub-Saharan Africa.
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Decline, %
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The MDG-5 target is to reduce by three-quarters the maternal mortality ratio between 1990 and 2015 and to achieve, by 2015, universal access to reproductive health. MDG-5 is the most off track Millennium Development Goal of all. The failure to make more rapid progress on reducing maternal mortality is the most serious wound on the body of global health. This failure indicates that, whatever the rhetoric of reports and speeches, the international community has failed women, and failed them badly. Many reasons will be given in mitigation. But the underlying cause of failure is that development partners have simply not been sufficiently interested in strengthening the systems of health care that women need during pregnancy and childbirth. Most countries are a considerable distance from reaching zero % unmet need [8]. In 2010, the UN Secretary General launched the campaign “Every Woman Every Child”, with the subsequent creation of the Commission on Information and Accountability for Women's and Children's Health [9]. Maternal death has been recently categorized in nine main causes: maternal hemorrhage, maternal sepsis and other pregnancy-related infections, hypertensive disorders of pregnancy, obstructed labor, abortion, other direct maternal disorders, indirect maternal disorders, HIV, and late maternal deaths. In addition, they were identified four different time windows: deaths occurring antepartum (before onset of labor), deaths occurring intrapartum or during the immediate postpartum period (up to 24 h after delivery), deaths occurring during the subacute and delayed postpartum periods (24 h to 42 days after delivery), and late maternal deaths (43 days to 1 year after delivery) [10].
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Over the past decades, child mortality in high-income countries has fallen to very low rates and currently it represents only 8% of the global burden of childhood mortality [11]. However, up to 25% of these deaths could be considered preventable. Rates vary considerably among sex, age, and different countries. A recent report on neonatal mortality in England and Wales demonstrated that the highest rates of child mortality are in infancy, especially those within the first 28 days of life [12]; the most common causes of death are perinatal and congenital diseases. Hypoxic–ischemic injury and congenital malformations, particularly congenital heart defects, are the main causes of death in full-term newborns, accounting for 58% of all neonatal deaths. On the other hand, in preterm babies 21% of deaths is due to malformations; two-thirds of
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all deaths are caused by respiratory disease and intraventricular or periventricular hemorrhage, sometimes closely related with prematurity. The risk of neonatal death from malformation is inversely correlated with the gestational age at birth, being higher in premature babies compared with term babies. In babies born before 32 weeks of gestation, infection, including necrotising enterocolitis, lung disease, and brain damage are very common causes of death. In England between one month and 19 years of age, nearly 80% of annual child deaths (1600) is due to: neurological, respiratory, and cardiovascular disorders; infections; and cancers. These data can be considered comparable with those of other European countries, calling for a substantial improvement of public health measures for the prevention of children's deaths from acquired natural causes. Suggested strategies for the reduction of child mortality can be condensed in three recommendations: (a) to accurately monitor the effectiveness of services delivered across the patient pathway by using a dataset of child mortality indicators; (b) to shift delivery of services from a hospital-centric to a community-centric model of care, being the latter more appropriate for children with life-long chronic disorders, complex disability, and obesity; (c) to reduce inequality by more efficient socioeconomic policies, since they significantly affect child survival and health outcomes [13].
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One child dies every 20 s from a disease preventable by vaccine. An estimated 1.5 million children died in 2011 from vaccine-preventable diseases. Every child deserves vaccination. Nearly one in five infants is still unprotected against killer diseases because she or he has not been immunized. The Convention on the Rights of the Child states that all children must have equal access to adequate healthcare; vaccination is a cornerstone of healthcare. The Global Vaccine Action Plan (GVAP) was endorsed by the 194 Member States of the World Health Organization (WHO) Assembly in May 2012 to achieve the Decade of Vaccines vision by delivering universal access to immunization. Under the GVAP adopted by the World Health Assembly in May 2012, the international community has committed to achieve 90% immunization coverage at the national level by 2020 to all children, regardless of where they are born, who they are or where they live. UNICEF supports national immunization programs in several ways [14]. One critical area is the cold chain and logistics (CCL) system, as vaccines are biological products that must be kept within a narrow temperature range, usually 2–8 degrees Centigrade. The cold chain refers to the storage and transport equipment that enables vaccine to be kept at this temperature from the point of manufacture to the point of use in an immunization session or a clinic. The CCL system includes: (a) a management information system capable of collecting and reporting data; (b) a stock inventory control system to ensure proper management of all supplies; (c) storage and warehousing of adequate capacity and quality to ensure their
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were caused by sepsis and meningitis (12%), pneumonia (10%) or diarrhea (2%). These diseases are highly treatable, provided simple interventions and basic treatment knowledge are available [7]. Another 34% of neonatal deaths, the majority of them preventable, were caused by complications from preterm birth.
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8. Beyond the Millennium Development Goals: post-2015 perspectives
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Within 2015, the period of the Millennium Development Goals (MDGs) will end, and the 189 signatory countries will take stock of what has been achieved. Most countries are not achieving MDGs 4 and 5; nevertheless, progress has accelerated over the past five years, suggesting that further gains are possible with continued, intensified programs. This means that there is the absolute need to promote a new global framework for after 2015, proposing updated versions for MDGs 4 and 5 [17] as well as innovative strategies for reducing malnutrition, the most important factor negatively impacting maternal and child health [18]. Between 1990 and 2013, the annual number of deaths among children younger than 5 years of age has fallen to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48% reduction from the 12.6 million deaths (uncertainty range, 12.4 to 12.9 million). This trend was obtained despite an increased number of births in many high-burden countries during the same time period. The sobering realization is that even in countries that will reach their MDG 4 and 5 targets, many will still have high numbers of deaths, with much scope for improvement. By 2050, 1 in every 3 births will be African. Under-5 deaths will continue to concentrate in Africa. Within countries, those deaths are likely to be concentrated still further among the poorest populations. Accelerating the reduction in under-5 mortality is possible by expanding effective preventive and curative interventions that target the main causes of post-neonatal deaths (pneumonia, diarrhea, malaria and under-nutrition) and the most vulnerable newborn babies and children. The post-2015 agenda should include the urgent need to drastically reduce several conditions currently hampering the improvement in the health and wellbeing of women, adolescent girls and children: stillbirths; unsafe abortions; child marriage; violence against women and girls (i.e., female genital mutilation); rape and violence in conflict situations; gender inequality perpetuated by religious belief. The global community must ensure high quality health care for women and children as a universal right, not a local privilege. Post2015 perspectives should include a new vision on what means health and how to deliver it, moving away from the concept of absence of disease and survival towards the integration of wellbeing, resilience, and capability [19]. Health should become the driver of poverty reduction. To do it, there is the need to invest in prevention, to promote equity by destroying social and cultural barriers, to launch education campaigns and programs for citizens and health care workers, and ultimately to improve environmental conditions (i.e., reducing pollution). Early diagnosis of maternal and neonatal diseases could significantly improve the care of babies and mothers. Therefore, there is the need to promote new experimental and clinical researches in the fields of perinatal medicine as well as in molecular biology [20].
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UNICEF is a leading partner in the Global Alliance for Vaccines and Immunization (GAVI), a far-reaching public–private partnership dedicated to increasing children's access to vaccines in poor countries. GAVI supports the poorest countries of the world to expand access to lifesaving vaccines. The Alliance works to strengthen and expand routine immunization services and support the introduction of new and under-used vaccines, including those that protect against hepatitis B and Hib disease. The ultimate objective: establish immunization programs that will function smoothly year after year as part of solid primary health care systems. Over 370 million children had received GAVIsupported vaccines by the end of 2012. With the additional US $4.3 billion pledged in London in 2011, GAVI has been able to accelerate the roll out of vaccination programs worldwide. For example, by the end of 2012, pneumococcal vaccine had been added to the routine immunization systems of 24 countries (and rotavirus vaccine in 12 countries) [15]. In 2012, Ghana and Tanzania simultaneously launched both vaccines, as the GAVI report says, “establishing Africa's leadership in fighting vaccine-preventable deaths” [16]. A new funding window was also opened to provide access to the HPV vaccine. Over 85% of deaths from cervical cancer occur in low- and middle-income countries. In 2013, the first GAVI-supported HPV vaccines were delivered to Kenya, Ghana, Madagascar, Malawi, Niger, Rwanda, Sierra Leone, Tanzania, and Lao PDR are additional demonstration countries. By 2015, one million girls will have received the HPV vaccine in over 20 countries. By 2020, over 30 million girls in more than 40 countries will have been vaccinated against HPV with GAVI support. With new initiatives launched this year on pneumonia and diarrhea, for example, we see great opportunities for GAVI to integrate more of its work with related projects that will reinforce, support, and sustain its core activities on vaccines. In 2011, the financial replenishment of GAVI gave an additional US $4.3 billion towards vaccine coverage. In 2012, new commitments to
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family planning delivered US $2.6 billion to provide 120 million women with access to modern contraceptives by 2020. And in June, 2013, US $4.15 billion was pledged to save 1.7 million lives from under-nutrition. These annual global campaigns, together with initiatives such as the Commodities Commission, are an important means to bring international attention to specific, and often neglected, dimensions of women's and children's health. They are essential public displays of, and material contributions to, political commitment that bring new resources to bear on achieving MDGs 4 and 5.
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integrity; (d) a distribution/maintenance system for efficient transport to every immunization session; and (e) sufficient number of trained personnel at every level, with adequate supervision. When the Expanded Programme on Immunization (EPI) was launched in 1974, less than 5% of the world's children were immunized during their first year of life against six killer diseases: polio; diphtheria; tuberculosis; pertussis (whooping cough); measles; tetanus. Currently, 83% of the world's children under-1 year of age have received these life-saving vaccinations. Increasing numbers of countries, including low-income countries, are adding new and under-used vaccines, like Hepatitis B, Haemophilus influenzae type b (Hib) and yellow fever vaccine to their routine infant immunization schedules. However, onefifth of the world's children – about 22.4 million infants – are not immunized against these killer diseases. UNICEF is pioneering new technology applications via SMS and smartphones to track immunization and keep children up to date on their vaccine schedules. In countries with low immunization rates like the Republic of Congo, UNICEF and frontline health workers are using SMS to register births, follow young families and report infant vaccinations. To reach unimmunized children in Uganda, mobile phone innovations track vaccine availability, disease outbreaks, immunization coverage and quality of medical services. In conflict situations, UNICEF collaborates with United Nations' partners to negotiate temporary cease-fires and accept ‘Days of Tranquility’ to give health workers access to children for vaccination campaigns. UNICEF also engages with the international and local press to relay information about where vaccinations will take place and to encourage that safe passage agreements be respected. At the end of 2012, UNICEF procured more than 500 million immunization syringes, nearly US $30 million worth of ‘cold chain’ equipment, over 1 billion doses of oral polio vaccines, 161 million doses of measles vaccines, 134 million doses of the pentavalent vaccine, which protects against diphtheria, tetanus, whooping cough, hepatitis and Hib with one jab.
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9. Laboratory medicine as a tool for improving maternal and child 400 survival 401 Prevention and early diagnosis are the keywords for reducing maternal and child mortality rate worldwide. In this respect, laboratory medicine can play a strategic role by promoting new diagnostic tests with high sensitivity and specificity. In addition, to improve human health, scientific discoveries must be translated into practical applications.
Please cite this article as: Guerrera G, Neonatal and pediatric healthcare worldwide: A report from UNICEF, Clin Chim Acta (2015), http:// dx.doi.org/10.1016/j.cca.2015.03.004
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[1] United Nations Inter-agency Group for Child Mortality Estimation. Levels and trends in child mortality: report 2013. New York, USA: UNICEF; 2013. [http://www.unicef. org/media/files/2013_IGME_child_mortality_Report.pdf. Accessed September, 6th, 2014]. [2] Bhutta ZA, Black RE. Global maternal, newborn, and child health — so near and yet so far. N Engl J Med 2013;369:2226–35. [3] Wang H, Liddell CA, Coates MM, et al. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014 [pii: S0140-6736(14)60497-9]. [4] Goli S, Arokiasamy P. Maternal and child mortality indicators across 187 countries of the world: converging or diverging. Glob Public Health 2014;9:342–60. [5] Wardlaw T, You D, Newby H, Anthony D, Chopra M. Child survival: a message of hope but a call for renewed commitment in UNICEF report. Reprod Health 2013;10:64. [6] Cooper PA. The challenge of reducing neonatal mortality in low- and middle-income countries. Pediatrics 2014;133:4–6. [7] Thea D, Qazi S. Neonatal mortality—4 million reasons for progress. Lancet 2008; 371(9628):1893–5. [8] Lozano R, Wang H, Foreman KJ, et al. Progress towards millennium development goals 4 and 5 on maternal and child mortality: an updated systematic analysis. Lancet 2011;378:1139–65. [9] WHO, UNICEF, UN Population Fund, World Bank. Trends in maternal mortality: 1990 to 2010. Available at http://www.unfpa.org/webdav/site/global/shared/documents/ publications/2012/Trends_in_maternal_mortality_A4-1.pdf; 2012. [accessed Jan 31, 2014]. [10] Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, et al. Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384(9947):980–1004. [11] Fraser J, Sidebotham P, Frederick J, Covington T, Mitchell EA. Learning from child death review in the USA, England, Australia, and New Zealand. Lancet 2014; 384(9946):894–903. [12] Sidebotham P, Fraser J, Fleming P, Ward-Platt M, Hain R. Patterns of child death in England and Wales. Lancet 2014;384(9946):904–14. [13] Sidebotham P, Fraser J, Covington T, et al. Understanding why children die in highincome countries. Lancet 2014;384(9946):915–27. [14] Duclos P, Dumolard L, Abeysinghe N, et al. Progress in the establishment and strengthening of national immunization technical advisory groups: analysis from the 2013 WHO/UNICEF joint reporting form, data for 2012. Vaccine 2013;31: 5314–20. [15] [No authors listed]WHO Global rotavirus surveillance network—a strategic review of the first 5 years (2008–2012). EMBO Mol Med 2014;6:708–20. [16] Canavan ME, Sipsma HL, Kassie GM, Bradley EH. Correlates of complete childhood vaccination in East African countries. PLoS ONE 2014;9:e95709. [17] Requejo JH, Bryce J, Barros AJ, et al. Countdown to 2015 and beyond: fulfilling the health agenda for women and children. Lancet 2014 [pii: S0140-6736(14)60925-9]. [18] Requejo JH, Bhutta ZA. The post-2015 agenda: staying the course in maternal and child survival. Arch Dis Child 2015;100(Suppl. 1):S76–81. [19] [No Authors listed]Women, children, and adolescents: the post-2015 agenda. Lancet 2014;384:1159. [20] Souza JP, Widmer M, Gülmezoglu AM, et al. Maternal and perinatal health research priorities beyond 2015: an international survey and prioritization exercise. Reprod Health 2014;11:61. [21] Arbuckle MR, Gordon JA, Pincus HA, Oquendo MA. Bridging the gap: supporting translational research careers through an integrated research track within residency training. Acad Med 2013;88:759–65. [22] Mussap M, Antonucci R, Noto A, Fanos V. The role of metabolomics in neonatal and pediatric laboratory medicine. Clin Chim Acta 2013;426:127–38. [23] Patti GJ, Yanes O, Siuzdak G. Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 2012;13:263–9. [24] Ramautar R, Berger R, van der Greef J, Hankemeier T. Human metabolomics: strategies to understand biology. Curr Opin Chem Biol 2013;17:841–6. [25] Mussap M, Fanos V. Reducing neonatal mortality and expenditure in the era of health care crisis: is it possible? J Matern Fetal Neonatal Med 2012;25(Suppl. 5):1–3. [26] Dessì A, Cesare Marincola F, Masili A, Gazzolo D, Fanos V. Clinical metabolomics and nutrition: the new frontier in neonatology and pediatrics. Biomed Res Int 2014; 2014:981219. [27] UNICEF. Committing to child survival: a promise renewed progress report 2013. New York. http://www.unicef.org/publications/files/APR_Progress_Report_2013_9_ Sept_2013.pdf; 2013. [Accessed September, 6th, 2014].
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A revitalized commitment to child survival towards the ultimate aim of ending preventable child deaths is essential. A Promise Renewed (the call to action spearheaded by UNICEF and the US Agency for International Development to end all preventable child deaths by 2035) is such a commitment and more than 170 countries have signed on to it. Countries, the United Nations and its agencies, civil society and private sector organizations must commit to redouble their efforts to reduce child mortality and include this commitment in the post-2015 agenda. Contrary to popular belief, achieving reductions in maternal, neonatal and child mortality does not require expensive health care. There is evidence to show that significant progress can be made through the delivery of costeffective, proven interventions at the community level. Millions of mothers and children can be saved through essential low cost health care (State of the World’s Mothers 2008) designed based on the realities of the communities where the services are being provided. Investment in front-line health workers and support systems is critical, yet health
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budgets are heavily invested in tertiary care—a level of care that the majority of women and children never reach. Care at birth brings a triple return on investment, saving mothers, newborns and unborn children. Scaling up low-cost solutions to address preterm birth could reduce these deaths by three-quarters, notably with antenatal steroid injections to women in preterm labor and with kangaroo mother care, where the preterm baby is held skin to skin with their mother [27].
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Such discoveries typically begin at “the bench” with basic research and then progress to the clinical level, or the patient’s “bedside.” Again, laboratory medicine is a valuable tool for closing the gap between the bench and the bedside research [21]. The rapid development of methods based on metabolomics studies may be considered a paradigmatic example of how sophisticated research can be translated into clinical practice [22]. Laboratory medicine was based for a long time on the measurement of singles metabolites (substrates, enzymes, proteins, hormones, ions, and various other biochemical substances) representing a source of information related with health and disease. After the publication of the first full genome sequence in the mid-1990s, the rapid development of a new generation of diagnostic tests, including the ability of high throughput ‘omics’ platforms for profiling a large number of analytes in a single array, has radically changed the role of clinical pathologists. This global innovation in laboratory medicine will open new perspectives for reducing the gap between new discoveries from experimental studies into clinically available tests. Among ‘omics’ (genomics, transcriptomics, proteomics, etc.), metabolomics offers several advantages based on the fact that it can be considered the link between genotypes and phenotypes, being metabolites the ultimate response of biological systems either to genetic or environmental changes [23]. A large amount of metabolomics studies from the literature have undeniably demonstrated that changes in the metabolic profile allow: (a) a very early identification of subjects at risk to develop a disease, much earlier than any other laboratory test, even in the fetal life; (b) an accurate recognition of the effectiveness of the therapeutic treatment; (c) to reduce drastically any overlap between subjects with either a disease or at risk to develop a disease with healthy subjects; (d) to accurately predict patients outcome on the basis of differences between metabolic profiles and with a minimal or null rate of false positive and false negative results; (e) implementation of personalized medicine in clinical practice [24]. Metabolomics is opening encouraging expectations for improving the care in the early infancy and in childhood: as reported elsewhere [25], one of the most exciting challenges is the possibility to transform experimental results from metabolomics studies into lowcost devices (e.g., dipsticks) easily usable by anyone (e.g., parents) for the early, accurate identification of severe diseases very common in low-income countries, like sepsis, necrotizing enterocolitis, acute kidney injury, and many other critical clinical conditions. A recent study has demonstrated the importance of metabolomics for investigating the metabolic changes due to malnutrition (insufficient as well as excessive nutrition), both in fetal and post-natal life, including the effects of diet in pediatrics [26]. The definition of the interactions between nutrients and cell metabolites could lead to the ‘personalized nutrition’, tailored to the single genome of each child.
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