Effectiveness of bubble continuous positive airway pressure for treatment of children aged 1-59 months with severe pneumonia and hypoxaemia in Ethiopia: a pragmatic cluster-randomised controlled trial.

BACKGROUND: The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia. METHODS: This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed. FINDINGS: From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP. INTERPRETATION: In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings. FUNDING: SIDA Sweden and Grand Challenges Ethiopia.

Prevalence and causes of ocular disorders and visual impairment among preterm children in Ethiopia.

OBJECTIVE: The aim of this study was to determine the prevalence, causes of ocular disorders and visual impairment among preterm children previously admitted to neonatal intensive care units in Addis Ababa, Ethiopia. METHODS AND ANALYSIS: A prospective screening survey was conducted from February to June 2019 at the paediatric eye clinic of Menelik II Hospital. Children who were preterm at birth and who attended the eye clinic were included in the study. Data on demographic and neonatal characteristics, neonatal and maternal comorbidities and ocular disorders were collected. OR and univariate analysis were used to identify predictors of ocular diseases and visual impairment. RESULTS: There were 222 children included in the study with a mean age at presentation of 2.62 years (range 2.08-6.38 years), mean gestational age 34.11 weeks (range 30-36) weeks and mean birth weight 1941.72 g (range 953-3500 g). Nearly two-thirds had ocular disorders with refractive error (51.8%), strabismus (11.3%) and a history of retinopathy of prematurity (ROP) (7.2%) being more common. One-fourth of the children had visual impairment, and the prevalence of amblyopia was 40.1%. Uncorrected refractive errors, strabismus and ROP were causes for visual impairment. CONCLUSION: Visual impairment and amblyopia are common in Ethiopia. There is a need to develop a screening protocol for ocular disorders for preterm children to enhance early detection and prevention of childhood visual impairment.

Predictors of time to full enteral feeding in low birth weight neonates admitted to neonatal intensive care unit: a prospective follow up study.

BACKGROUND: Survival of LBW infants has increased in recent years because of novel perinatal interventions, but the introduction and advancement of enteral feeds for low birth weight infants is challenging. In Ethiopia the proportion of low birth weight infants is thought to be 17.3%. The purpose of this study was to determine the time to full enteral feeding (FEF) and its predictors in LBW neonates admitted to neonatal intensive care unit in selected hospitals of Addis Ababa, Ethiopia. METHOD: An institutional based prospective follow up study was conducted from March 15 to June 15, 2022 among 282 LBW neonates admitted to six randomly selected hospitals. Both primary and secondary data was used by interviewing mothers and prospective medical chart review of neonates. The Cox regression model was used and variables having a p-value less than 0.05 with 95% CIs in a multivariable analysis were declared as statistically significant association with time to full enteral feeding. RESULT: Out of 282 neonates involved in this study, 211 (74.8%) of them reached at FEF. The overall median time to full enteral feeding was 5 days. Predictors significantly associated with time to full enteral feeding were educational level, birth weight, cesarean delivery, hospital acquired infection, being on antibiotics, age at initiation of trophic feeding, routine gastric residual evaluation and NICU location (hospital). CONCLUSIONS: This study demonstrated the difficulty of understanding which low birth weight neonate will attain FEF in a timely manner and factors that affect time to FEF. There is a delay in full enteral feeding achievement among low birth weight neonates and there is a great deal of heterogeneity of practice among health care providers regarding feeding of infants as it was evidenced by a variation in feeding practice among hospitals. Nutrition should be considered as part of the management in neonatal intensive care units since low birth weight neonates are developing edematous malnutrition while they are in the NICU. There should be standard feeding protocol to avoid heterogeneity of practice and additional study should be conducted for each categories of GA and BW with long follow up time.

A prospective observational study of nurses performing minimally invasive tissue sampling of brain, liver, and lung tissues among deceased neonates and stillbirths in Ethiopia.

Background: With a neonatal mortality rate of 33 per 1,000 live births in 2019, Ethiopia is striving to attain the Sustainable Development Goal target of 12 deaths per 1,000 live births by 2030. A better understanding of the major causes of neonatal mortality is needed to effectively design and implement interventions to achieve this goal. Minimally Invasive Tissue Sampling (MITS), an alternative to conventional autopsy, requires fewer resources and through task-shifting of sample collection from pathologists to nurses, has the potential to support the expansion of pathology-based post-mortem examination and improve mortality data. This paper evaluates the accuracy and adequacy of MITS performed by nurses at a tertiary and general hospital and in the home of the deceased. Methods: Nurses in a tertiary and general hospital in Ethiopia were trained in MITS sample collection on neonatal deaths and stillbirths using standardized protocols. MITS sample collection was performed by both pathologists and nurses in the tertiary hospital and by nurses in the general hospital and home-setting. Agreement in the performance of MITS between pathologists and nurses was calculated for samples collected at the tertiary hospital. Samples collected by nurses in the general hospital and home-setting were evaluated for technical adequacy using preestablished criteria. Results: One hundred thirty-nine MITS were done: 125 in hospitals and 14 inside homes. There was a perfect or almost perfect agreement between the pathologists and the nurses in the tertiary hospital using Gwet's agreement interpretation criteria. The adequacy of MITS samples collected by nurses in the general hospital was more than 72% when compared to the preset criteria. The adequacy of the MITS sampling yield ranged from 87% to 91% on liveborn neonatal deaths and 76% for the liver, right and left lungs and 55% for brain tissues in stillbirths. Conclusions: This study demonstrated that task-shifting MITS sample collection to nurses can be achieved with comparable accuracy and adequacy as pathologists. Our study showed that with standardized training and supportive supervision MITS sample collection can be conducted by nurses in a tertiary, general hospital and, at the home of the deceased. Future studies should validate and expand on this work by evaluating task-shifting of MITS sample collection to nurses within community settings and with larger sample sizes.

Retinopathy of prematurity among infants admitted to two neonatal intensive care units in Ethiopia.

OBJECTIVE: This study was conducted to determine the prevalence and risk factors for retinopathy of prematurity (ROP) in two neonatal intensive care units (NICUs) in Addis Ababa, Ethiopia. METHODS AND ANALYSIS: A prospective screening survey was conducted from June 2019 to June 2020 in two level 3 public NICUs. Infants with a birth weight (BW) of ≤1500 g or gestational age (GA) of ≤32 weeks and those with a BW of >1500 g and GA of >32 weeks with an unstable clinical course were included. Data on demographic and neonatal characteristics, neonatal and maternal comorbidities, and therapeutic interventions were collected. Logistic regression analysis was used to identify predictors of ROP. RESULTS: Two hundred and two infants were included: mean BW: 1658g (range: 700-2400 g) and mean GA: 32.4 weeks (range: 26-34 weeks). 32.2% had any stage of ROP, and 6.4% had Type 1 ROP. Lower BW, smaller GA and total days on oxygen were independent risk factors for severe ROP (Type 1 or worse). All 13 neonates with severe ROP were treated. CONCLUSION: ROP is emerging as a concern in Ethiopia. ROP screening should include neonates with BW of <1800 g or GAs of ≤33 weeks, but further studies are needed in level 2 and private NICUs. Screening guidelines need to be developed and implemented in all hospitals with NICUs.

Perception and experience of clinicians and caregivers in treating childhood severe pneumonia and hypoxemia using bubble continuous positive airway pressure in Ethiopian tertiary and general hospitals.

BACKGROUND: In low and middle-income countries (LMICs), severe pneumonia with hypoxemia is the leading cause of child deaths, even with the provision of WHO-recommended antibiotic therapy, oxygen therapy and other supportive care. Previous studies found positive outcomes from the use of bubble continuous positive airway pressure (bCPAP) for treating these children compared to the standard oxygen therapy. Due to lack of data on the perceptions and experiences of hospital health care workers and caregivers of children on the feasibility and acceptability of bCPAP in treating children with severe pneumonia and hypoxemia in real-life settings, we examined these issues in tertiary and general hospitals in Ethiopia. METHODS: As part of a three-stages clinical trial, this qualitative study was conducted in two tertiary (stage I) and two general (stage II) hospitals from September 2019 to July 2020. During stages I and II, we have consecutively enrolled children with severe pneumonia and hypoxemia and put them on bCPAP to examine its feasibility and acceptability by clinicians and parents. A total of 89 children were enrolled (49 from two tertiary and 40 from two general hospitals). Then qualitative data were collected through 75 repeated in-depth interviews by social-science experts with purposively selected 30 hospital health workers and 15 parents of 12 children who received bCPAP oxygen therapy in the hospitals. Interview data were supplemented by 6 observations in the hospitals. Data were analyzed using a thematic approach. RESULTS: Identified structural and functional challenges for the introduction of bCPAP in treating childhood severe pneumonia and hypoxemia in the study hospitals include: inadequate number of pulse oximeters; unavailability of nasal prongs with age-specific size; inadequate and non-functioning oxygen flow meters, concentrator, and cylinders; disruption in power-supply; and inadequate number of staff. The opportunities in introducing bCPAP oxygen therapy included the availability of a dedicated corner for the study patients situated in front of nurse's station, required medicines and satisfactory level of clinicians' knowledge and skills for treating severe pneumonia patients. Additionally, the identified operational challenges were occasional lack of bubbling in the water-filled plastic bottle, lack of stand for holding the water-filled plastic bottle, and delayed shifting of oxygen source from an oxygen concentrator to a cylinder, particularly during electricity disruption. Participants (clinicians and parents) expressed their satisfaction as bCPAP oxygen therapy was found to be simple to handle, children had ease of breathing and recovered fast without major ill effects. CONCLUSION: Our study identified some important structural, functional, and operational challenges that need to be addressed before implementation of bCPAP oxygen therapy especially in frontline general hospitals with limited resources. In spite of these observed challenges, the clinicians and caregivers were highly satisfied with the overall performance of bCPAP oxygen therapy.

Effectiveness of Bubble Continuous Positive Airway Pressure (BCPAP) for Treatment of Children Aged 1-59 Months with Severe Pneumonia and Hypoxemia in Ethiopia: A Pragmatic Cluster Randomized Controlled Clinical Trial.

Despite the beneficial effect of bubble continuous positive airway pressure (BCPAP) oxygen therapy for children with severe pneumonia under the supervision of physicians that has been shown in different studies, effectiveness trials in developing country settings where low-flow oxygen therapy is the standard of care are still needed. Thus, the aim of this study is to assess the effectiveness of bubble CPAP oxygen therapy compared to the WHO standard low-flow oxygen therapy among children hospitalized with severe pneumonia and hypoxemia in Ethiopia. This is a cluster randomized controlled trial where six district hospitals are randomized to BCPAP and six to standard WHO low-flow oxygen therapy. The total sample size is 620 per arm. Currently, recruitment of the patients is still ongoing where the management and follow-up of the enrolled patients are performed by general physicians and nurses under the supervision of pediatricians. The primary outcome is treatment failure and main secondary outcome is death. We anticipate to complete enrollment by September 2022 and data analysis followed by manuscript writing by December 2022. Findings will also be disseminated in December 2022. Our study will provide data on the effectiveness of BCPAP in treating childhood severe pneumonia and hypoxemia in a real-world setting.

"Death audit is a fight" - provider perspectives on the ethics of the Maternal and Perinatal Death Surveillance and Response (MPDSR) system in Ethiopia.

BACKGROUND: Maternal and neonatal health are regarded as important indicators of health in most countries. Death auditing through, for example, the Maternal and Perinatal Death Surveillance and Response (MPDSR) is viewed as key to preventing maternal and newborn mortality. However, little is known about the implications of implementing perinatal auditing for healthcare professionals in low-income contexts. This study aimed to explore the ethical and practical consequences clinicians experience concerning MPDSR reporting practices in Ethiopia.  METHODS: Qualitative semi-structured in-depth individual interviews were conducted with 16 healthcare workers across professions at selected facilities in Ethiopia. The interview questions were related to clinicians' experiences with, and perceptions of, death auditing. Their strategies for coping with newborn losses and the related reporting practices were also explored. The material was analyzed following systematic text condensation, and the NVivo11 software was used for organizing and coding the data material. RESULTS: Participants experienced fear of punishment and blame in relation to the perinatal death auditing process. They found that auditing did not contribute to reducing perinatal deaths and that their motivation to stick to the obligation was negatively affected by this. Performing audits without available resources to provide optimal care or support in the current system was perceived as unfair. Some hid information or misreported information in order to avoid accusations of misconduct when they felt they were not to blame for the baby's death. Coping strategies such as engaging in exceedingly larger work efforts, overtreating patients, or avoiding complicated medical cases were described. CONCLUSIONS: Experiencing perinatal death and death reporting constitutes a double burden for the involved healthcare workers. The preventability of perinatal death is perceived as context-dependent, and both clinicians and the healthcare system would benefit from a safe and blame-free reporting environment. To support these healthcare workers in a challenging clinical reality, guidelines and action plans that are specific to the Ethiopian context are needed.

Umbilical cord blood hematological parameters reference interval for newborns from Addis Ababa, Ethiopia.

BACKGROUND: Several factors like altitude, age, sex, pregnancy, socioeconomic status, life style and race influence hematological reference interval (RIs), which are critical to support clinical decisions and to interpret laboratory data in research. Currently there are no well-established RIs for cord blood hematological parameters of newborns in Ethiopia. This study aims to generate RIs for umbilical cord blood hematological parameters of newborns from Addis Ababa, Ethiopia. METHOD: A cross-sectional study was conducted from January 1 to March 31, 2019 on healthy, term newborns (37-42 weeks) with normal birth weight born to apparently healthy pregnant mothers who had met the eligibility criteria. From 139 newborns, 2-3ml cord blood was immediately collected from the clumped cord using EDTA tube. The samples were analyzed using Sysmex KX 21 hematology analyzer. Data was entered and the 2.5th and 97.5th percentiles (upper and lower reference limit) were determined using non parametric method by SPSS version 23. The non-parametric independent Mann-Whitney U test (Wilcoxon rank-sum test) was used to compare the distribution of the parameters between genders, modes of deliveries and gestational age. P value less than 0.05 was considered to declare statistical significance. RESULT: The median values and 95 % reference interval for umbilical cord blood hematological parameters of newborns were as follows: WBC = 12.4 [6.6-19.4] x109/L, RBC = 4.51 [3.55-5.52] x1012/L, HGB = 15.8 [12.4-19.7] g/dL, HCT = 45.9[37.9-56.3]%, MCV = 102.1[83.9-111.6] fL, MCH = 35.3 [29.4-39.1] pg, MCHC = 34.3 [32.3-37.4] %, PLT = 236 [146-438] x109/L, LYM = 37.5 [16.6-63.0] %, MXD = 7.9[1.7-15.8] %, NEU = 53.7[30.3-78.4] %, RDW = 15.6[12.0-19.0]%, PDW = 11.0[9.1-15.7]% and MPV = 9.4[8.1-11.8] fL. The current study found no significant difference between genders, except RDW (P = 0.01), and gestational age group, but there was significant difference for WBC (p = 0.007), RBC (p = 0.018) and Absolute NEU (p = 0.001) by delivery type where newborns delivered through caesarean section had lower values for these three parameters compared to those with spontaneous delivery. CONCLUSIONS: hematological reference intervals in cord blood were established for the first time from healthy newborns of Addis Ababa and its surrounding. The values are applicable for newborns from this area. Larger study throughout the country is warranted.

Antenatal Steroid Utilization in Ethiopia.

Background. Administration of antenatal corticosteroids to pregnant mothers is one of the most effective interventions to decrease preterm neonatal mortality. In this study we assessed antenatal steroid utilization by the mother and its effect on preterm babies. Method. Two years prospective, multicenter, observational study was conducted in selected hospitals of Ethiopia. Significance of the study outcomes was tested by chi-square and binary logistic regression. Result. Out of 4919 participants, 1575 preterm babies whose gestational ages were below 35 weeks were included in the study. Use of antenatal dexamethasone was 37.5% among study participants. The risk of early onset neonatal sepsis 235 (40.4%) was higher in preterm babies whose mother took antenatal dexamethasone (P-value .002) than those who did not. Conclusion. Antenatal dexamethasone use in our study was comparable with other low and middle-income countries. Risk of early onset neonatal sepsis was higher among infants whose mother took antenatal dexamethasone.

Hypothermia in Preterm Newborns: Impact on Survival.

Background. Globally, prematurity is the leading cause of neonatal mortality, and hypothermia is one of its contributing factors. The goal of this study was to determine the association between hypothermia and mortality. Methods. A prospective, multi-center, descriptive clinical study was conducted in 5 hospitals in Ethiopia. Axillary temperatures were taken at the time of admission to the newborn intensive care units (NICU) and followed during the NICU stay. Results. A total of 3852 premature neonates (<37 weeks) were admitted to the NICUs from July 2016 to May 2018. Of these infants, 1109 (28.8%) died and 2991 (79.6%) had hypothermia. Hypothermia was associated with perinatal asphyxia (89.5%), RDS (86.2%), and resuscitation at birth (82.7%). Admission temperatures in preterm newborns were inversely associated with mortality and morbidity. Conclusion. Hypothermia at admission is associated with neonatal mortality in premature neonates in Ethiopia. RDS and perinatal asphyxia were the main factors associated with hypothermia. The very high prevalence and association with mortality warrants quality improvement interventions.

Preterm Nutrition and Clinical Outcomes.

Background. In low-income countries, preterm nutrition is often inadequately addressed. The aim of the study was to assess the patterns of feeding and associated clinical outcomes of preterm neonates admitted to neonatal intensive care units in Ethiopia. Method. This was a multicenter, prospective study. Infants' clinical characteristics at birth, daily monitoring of feeding history, and weight measurements were collected. An outcome assessment was completed at 28 days. Result. For this analysis, 2560 infants (53% male) were eligible. The mean (SD) gestational age was 33.1 (2.2) weeks. During the hospital stay the proportion of infants on breast milk only, preterm formula, term formula, and mixed feeding was 58%, 27.4%, 1.6%, and 34.1%, respectively. Delay in enteral feeding was associated with increased risk of death (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.33-2.78; P < .001) and (OR = 5.06, 95% CI = 3.23-7.87; P < .001) for 1 to 3 and 4 to 6 days of delay in enteral feeding, respectively, after adjusting for possible confounders. The length of delay in enteral feeding was associated with increased risk of hypoglycemia (OR = 1.2, 95% CI = 1.1-1.2; P = .005). The mortality rate was lower in hospitals providing preterm formula more often (P = .04). Half of the infants continued losing weight at the time of discharge. Conclusion. Delayed enteral feeding significantly increases the risk of mortality before discharge and hypoglycemia in preterm infants in resource-limited settings. Ensuring adequate nutritional support of preterm infants is highly needed.

Hyperbilirubinemia in Preterm Infants Admitted to Neonatal Intensive Care Units in Ethiopia.

Background. Hyperbilirubinemia is prevalent and protracted in preterm infants. This study assessed the pattern of hyperbilirubinemia in preterm infants in Ethiopia. Methods. This study was part of multi-centered prospective, cross-sectional, observational study that determined causes of death among preterm infants. Jaundice was first identified based on clinical visual assessment. Venous blood was then sent for total and direct serum bilirubin level measurements. For this study, a total serum bilirubin level ≥5 mg/dL was taken as the cutoff point to diagnose hyperbilirubinemia. Based on the bilirubin level and clinical findings, the final diagnoses of hyperbilirubinemia and associated complications were made by the physician. Result. A total of 4919 preterm infants were enrolled into the overall study, and 3852 were admitted to one of the study's newborn intensive care units. Of these, 1779 (46.2%) infants were diagnosed with hyperbilirubinemia. Ten of these (0.6%) developed acute bilirubin encephalopathy. The prevalence of hyperbilirubinemia was 66.7% among the infants who were less than 28 weeks of gestation who survived. Rh incompatibility (P = .002), ABO incompatibility (P = .0001), and sepsis (P = .0001) were significantly associated with hyperbilirubinemia. Perinatal asphyxia (P-value = 0.0001) was negatively associated with hyperbilirubinemia. Conclusion. The prevalence of hyperbilirubinemia in preterm babies admitted to neonatal care units in Ethiopia was high. The major risk factors associated with hyperbilirubinemia in preterm babies in this study were found to be ABO incompatibility, sepsis, and Rh isoimmunization.

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

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.