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      Major causes of death in preterm infants in selected hospitals in Ethiopia (SIP): a prospective, cross-sectional, observational study

      research-article
      , Prof, MD a , * , , PhD b , , MD c , , Prof, MD a , , Prof, MD d , , Prof, PhD a , , MD a , , MD e , , MD f , , MD g , , MD e , , MD f , , MD g , , MD g , , MD f , , MD e , , MD g , , MSc e , , MD f , , MD j , , MD e , , MD a , , MD a , , MD a , , MD g , , MD e , , MD k , a , a , , PhD a , , MD e , , MD a , l , , MD i , , Prof, PhD h
      The Lancet. Global Health
      Elsevier Ltd

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          Summary

          Background

          Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia.

          Methods

          We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data.

          Findings

          Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28–31 weeks (512 [54%] of 952), 32–34 weeks (349 [18%] of 1975), and 35–36 weeks (159 [8%] of 1888).

          Interpretation

          Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death.

          Funding

          Bill & Melinda Gates Foundation.

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          Most cited references14

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          How Ethiopia achieved Millennium Development Goal 4 through multisectoral interventions: a Countdown to 2015 case study

          Summary Background 3 years before the 2015 deadline, Ethiopia achieved Millennium Development Goal 4. The under-5 mortality decreased 69%, from 205 deaths per 1000 livebirths in 1990 to 64 deaths per 1000 livebirths in 2013. To understand the underlying factors that contributed to the success in achieving MDG4, Ethiopia was selected as a Countdown to 2015 case study. Methods We used a set of complementary methods to analyse progress in child health in Ethiopia between 1990 and 2014. We used Demographic Health Surveys to analyse trends in coverage and equity of key reproductive, maternal health, and child health indicators. Standardised tools developed by the Countdown Health Systems and Policies working group were used to understand the timing and content of health and non-health policies. We assessed longitudinal trends in health-system investment through a financial analysis of National Health Accounts, and we used the Lives Saved Tool (LiST) to assess the contribution of interventions towards reducing under-5 mortality. Findings The annual rate of reduction in under-5 mortality increased from 3·3% in 1990–2005 to 7·8% in 2005–13. The prevalence of stunting decreased from 60% in 2000 to 40% in 2014. Overall levels of coverage of reproductive, maternal health, and child health indicators remained low, with disparities between the lowest and highest wealth quintiles despite improvement in coverage for essential health interventions. Coverage of child immunisation increased the most (21% of children in 2000 vs 80% of children in 2014), followed by coverage of satisfied demand for family planning by women of reproductive age (19% vs 63%). Provision of antenatal care increased from 10% of women in 2000 to 32% of women in 2014, but only 15% of women delivered with a skilled birth attendant by 2014. A large upturn occurred after 2005, bolstered by a rapid increase in health funding that facilitated the accelerated expansion of health infrastructure and workforce through an innovative community-based delivery system. The LiST model could explain almost 50% of the observed reduction in child mortality between 2000 and 2011; and changes in nutritional status were responsible for about 50% of the 469 000 lives saved between 2000 and 2011. These developments occurred within a multisectoral policy platform, integrating child survival and stunting goals within macro-level policies and programmes for reducing poverty and improving agricultural productivity, food security, water supply, and sanitation. Interpretation The reduction of under-5 mortality in Ethiopia was the result of combined activities in health, nutrition, and non-health sectors. However, Ethiopia still has high neonatal and maternal morbidity and mortality from preventable causes and an unfinished agenda in reducing inequalities, improving coverage of effective interventions, and strengthening multisectoral partnerships for further progress. Funding Bill & Melinda Gates Foundation and Government of Canada.
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            Causes of death in very preterm infants cared for in neonatal intensive care units: a population-based retrospective cohort study

            Background While there are good data to describe changing trends in mortality and morbidity rates for preterm populations, there is very little information on the specific causes and pattern of death in terms of age of vulnerability. It is well established that mortality increases with decreasing gestational age but there are limited data on the specific causes that account for this increased mortality. The aim of this study was to establish the common causes of hospital mortality in a regional preterm population admitted to a neonatal intensive care unit (NICU). Methods Retrospective analysis of prospectively collected data of the Neonatal Intensive Care Units' (NICUS) Data Collection of all 10 NICUs in the region. Infants <32 weeks gestation without major congenital anomalies admitted from 2007 to 2011 were included. Three authors reviewed all cases to agree upon the immediate cause of death. Results There were 345 (7.7%) deaths out of 4454 infants. The most common cause of death across all gestational groups was major IVH (cause-specific mortality rate [CMR] 22 per 1000 infants), followed by acute respiratory illnesses [ARI] (CMR 21 per 1000 infants) and sepsis (CMR 12 per 1000 infants). The most common cause of death was different in each gestational group (22–25 weeks [ARI], 26–28 weeks [IVH] and 29–31 weeks [perinatal asphyxia]). Pregnancy induced hypertension, antenatal steroids and chorioamnionitis were all associated with changes in CMRs. Deaths due to ARI or major IVH were more likely to occur at an earlier age (median [quartiles] 1.4 [0.3–4.4] and 3.6 [1.9–6.6] days respectively) in comparison to NEC and miscellaneous causes (25.2 [15.4–37.3] and 25.8 [3.2–68.9] days respectively). Conclusions Major IVH and ARI were the most common causes of hospital mortality in this extreme to very preterm population. Perinatal factors have a significant impact on cause-specific mortality. The varying timing of death provides insight into the prolonged vulnerability for diseases such as necrotising enterocolitis in our preterm population.
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              Neonatal mortality and coverage of essential newborn interventions 2010 - 2013: a prospective, population-based study from low-middle income countries

              Background Approximately 3 million neonatal deaths occur each year worldwide. Simple interventions have been tested and found to be effective in reducing the neonatal mortality. In order to effectively implement public health interventions, it is important to know the rates of neonatal mortality and understand the contributing risk factors. Hence, this prospective, population-based, observational study was carried out to inform these needs. Methods The Global Network’s Maternal Newborn Health Registry was initiated in the seven sites in 2008. Registry administrators (RAs) attempt to identify and enroll all eligible women by 20 weeks gestation and collect basic health data, and outcomes after delivery and at 6 weeks post-partum. All study data were collected, reviewed, and edited by staff at each study site. The study was reviewed and approved by each sites’ ethics review committee. Results Overall, the 7-day neonatal mortality rate (NMR) was 20.6 per 1000 live births and the 28-day NMR was 25.7 per 1000 live births. Higher neonatal mortality was associated with maternal age > 35 and <20 years relative to women 20-35 years of age. Preterm births were at increased risk of both early and 28-day neonatal mortality (RR 8.1, 95% CI 7.5-8.8 and 7.5, 95% CI 6.9-8.1) compared to term as were those with low birth weight (<2500g). Neonatal resuscitation rates were 4.8% for hospital deliveries compared to 0.9% for home births. In the hospital, 26.5% of deliveries were by cesarean section with an overall cesarean section rate of 12.5%. Neonatal mortality rates were highest in the Pakistan site and lowest in Argentina. Conclusions Using prospectively collected data with high follow up rates (99%), we documented characteristics associated with neonatal mortality. Low birth weight and prematurity are among the strongest predictors of neonatal mortality. Other risk factors for neonatal deaths included male gender, multiple gestation and major congenital anomalies. Breech presentation/transverse lie, and no antenatal care were also significant risk factors for neonatal death. Coverage of interventions varied by setting of delivery, with the overall population rate of most evidence-based interventions low. This study informs about risk factors for neonatal mortality which can serve to design strategies/interventions to reduce risk of neonatal mortality. Trial registration The trial is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475
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                Author and article information

                Contributors
                Journal
                Lancet Glob Health
                Lancet Glob Health
                The Lancet. Global Health
                Elsevier Ltd
                2214-109X
                11 July 2019
                August 2019
                11 July 2019
                : 7
                : 8
                : e1130-e1138
                Affiliations
                [a ]College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
                [b ]Social, Statistical and Environmental Health Sciences, Research Triangle Institute, Durham, NC, USA
                [c ]Bill & Melinda Gates Foundation, Seattle, WA, USA
                [d ]Ethiopian Pediatric Society, Addis Ababa, Ethiopia
                [e ]Jimma University, Jimma, Ethiopia
                [f ]University of Gondar, Gondar, Ethiopia
                [g ]St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
                [h ]Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA
                [i ]Global Child Health and Life Support, American Academy of Pediatrics, Itasca, IL, USA
                [j ]Zewditu Hospital, Addis Ababa, Ethiopia
                [k ]Neonatology Unit, Hôpitaux Universitaires de Genève, Geneva, Switzerland
                [l ]Women's and Children's Health Research Unit, KAHER, J N Medical College, Belgaum, India
                Author notes
                [* ]Correspondence to:Prof Lulu M Muhe, College of Health Sciences, Addis Ababa University, 2304 Addis Ababa, Ethiopia muhe1952@ 123456gmail.com
                Article
                S2214-109X(19)30220-7
                10.1016/S2214-109X(19)30220-7
                6639243
                31303299
                766255d0-9caf-4ea8-8326-e92614a51ca5
                © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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