Risk and accuracy of outpatient-identified hypoxaemia for death among suspected child pneumonia cases in rural Bangladesh: a multifacility prospective cohort study.

BACKGROUND: Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh. METHODS: We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult breathing (defined as suspected pneumonia) were enrolled in the study; because lower respiratory tract infection mortality mainly occurs in children younger than 1 year, the primary study population comprised children aged 3-11 months. Study physicians recorded WHO IMCI pneumonia guideline clinical signs and peripheral arterial oxyhaemoglobin saturations (SpO2) in room air. They treated children with pneumonia with antibiotics (oral amoxicillin [40 mg/kg per dose twice per day for 5-7 days, as per local practice]), and recommended oxygen, parenteral antibiotics, and hospitalisation for those with an SpO2 of less than 90%, WHO IMCI danger signs, or severe malnutrition. Community health workers documented the children's vital status and the date of any vital status changes during routine household surveillance (one visit to each household every 2 months). The primary outcome was death at 2 weeks after enrolment in children aged 3-11 months (primary study population) and 12-35 months (secondary study population). Primary analyses included estimating the outpatient prevalence, mortality risk, and prognostic accuracy of hypoxaemia for death in children aged 3-11 months with suspected pneumonia. Risk ratios were produced by fitting a multivariable model that regressed predefined SpO2 ranges (<90%, 90-93%, and 94-100%) on the primary 2-week mortality outcome (binary outcome) using Poisson models with robust variance estimation. We established the prognostic accuracy of WHO IMCI guidelines for death with and without varying SpO2 thresholds. FINDINGS: Participants were recruited between Sept 1, 2015, to Aug 31, 2017. During the study period, a total of 7440 children aged 3-35 months with the first suspected pneumonia episode were enrolled, of whom 3848 (54·3%) with an attempted pulse oximeter measurement and 2-week outcome were included in our primary study population of children aged 3-11-months. Among children aged 3-11 months, an SpO2 of less than 90% occurred in 102 (2·7%) of 3848 children, an SpO2 of 90-93% occurred in 306 (8·0%) children, a failed SpO2 measurement occurred in 67 (1·7%) children, and 24 (0·6%) children with suspected pneumonia died. Compared with an SpO2 of 94-100% (3373 [87·7%] of 3848), the adjusted risk ratio for death was 10·3 (95% CI 3·2-32·3; p<0·001) for an SpO2 of less than 90%, 4·3 (1·5-11·8; p=0·005) for an SpO2 of 90-93%, and 11·4 (3·1-41·4; p<0·001) for a failed measurement. When not considering pulse oximetry, of the children who died, WHO IMCI guidelines identified only 25·0% (95% CI 9·7-46·7; six of 24 children) as eligible for referral to hospital. For identifying deaths, in children with an SpO2 of less than 90% WHO IMCI guidelines had a 41·7% sensitivity (95% CI 22·1-63·4) and 89·7% specificity (88·7-90·7); for children with an SpO2 of less than 90% or measurement failure the guidelines had a 54·2% sensitivity (32·8-74·4) and 88·3% specificity (87·2-89·3); and for children with an SpO2 of less than 94% or measurement failure the guidelines had a 62·5% sensitivity (40·6-81·2) and 81·3% specificity (80·0-82·5). INTERPRETATION: These findings support pulse oximeter use during the outpatient care of young children with suspected pneumonia in Bangladesh as well as the re-evaluation of the WHO IMCI currently recommended threshold of an SpO2 less than 90% for hospital referral. FUNDING: Fogarty International Center of the National Institutes of Health (K01TW009988), The Bill & Melinda Gates Foundation (OPP1084286 and OPP1117483), and GlaxoSmithKline (90063241).

Clinical hypoxemia score for outpatient child pneumonia care lacking pulse oximetry in Africa and South Asia.

Background: Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia. Methods: This was a retrospective pooled analysis of two outpatient datasets of 3-35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO2 < 93% and <90%: (1) Integrated Management of Childhood Illness guidelines, (2) WHO-composite guidelines, (3) Independent variable least absolute shrinkage and selection operator (LASSO); (4) Composite variable LASSO. Results: 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO2 < 93% and ≥94%; model predictive capacities remained moderate after adjusting for potential overfitting (C-statistic 0.74 and 0.75). The IMCI and WHO-composite models had poorer discrimination (C-statistic 0.56 and 0.68) and identified 20.6% and 56.8% of SpO2 < 93% cases. The highest score stratum of the independent and composite LASSO models identified 46.7% and 49.0% of SpO2 < 93% cases. Both LASSO models had similar performance for a SpO2 < 90%. Conclusions: In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases than the WHO guidelines. Score external validation and implementation are needed.

Digital auscultation as a novel childhood pneumonia diagnostic tool for community clinics in Sylhet, Bangladesh: protocol for a cross-sectional study.

INTRODUCTION: The WHO's Integrated Management of Childhood Illnesses (IMCI) algorithm for diagnosis of child pneumonia relies on counting respiratory rate and observing respiratory distress to diagnose childhood pneumonia. IMCI case defination for pneumonia performs with high sensitivity but low specificity, leading to overdiagnosis of child pneumonia and unnecessary antibiotic use. Including lung auscultation in IMCI could improve specificity of pneumonia diagnosis. Our objectives are: (1) assess lung sound recording quality by primary healthcare workers (HCWs) from under-5 children with the Feelix Smart Stethoscope and (2) determine the reliability and performance of recorded lung sound interpretations by an automated algorithm compared with reference paediatrician interpretations. METHODS AND ANALYSIS: In a cross-sectional design, community HCWs will record lung sounds of ~1000 under-5-year-old children with suspected pneumonia at first-level facilities in Zakiganj subdistrict, Sylhet, Bangladesh. Enrolled children will be evaluated for pneumonia, including oxygen saturation, and have their lung sounds recorded by the Feelix Smart stethoscope at four sequential chest locations: two back and two front positions. A novel sound-filtering algorithm will be applied to recordings to address ambient noise and optimise recording quality. Recorded sounds will be assessed against a predefined quality threshold. A trained paediatric listening panel will classify recordings into one of the following categories: normal, crackles, wheeze, crackles and wheeze or uninterpretable. All sound files will be classified into the same categories by the automated algorithm and compared with panel classifications. Sensitivity, specificity and predictive values, of the automated algorithm will be assessed considering the panel's final interpretation as gold standard. ETHICS AND DISSEMINATION: The study protocol was approved by the National Research Ethics Committee of Bangladesh Medical Research Council, Bangladesh (registration number: 09630012018) and Academic and Clinical Central Office for Research and Development Medical Research Ethics Committee, Edinburgh, UK (REC Reference: 18-HV-051). Dissemination will be through conference presentations, peer-reviewed journals and stakeholder engagement meetings in Bangladesh. TRIAL REGISTRATION NUMBER: NCT03959956.

Prenatal Environmental Metal Exposure and Preterm Birth: A Scoping Review.

Preterm birth (PTB) and its complications are the leading causes of under-five year old child deaths, accounting worldwide for an estimated one million deaths annually. The etiology of PTB is complex and multifactorial. Exposures to environmental metals or metalloids are pervasive and prenatal exposures to them are considered important in the etiology of PTB. We conducted a scoping review to determine the extent of prenatal exposures to four metals/metalloids (lead, mercury, cadmium and arsenic) and their association with PTB. We reviewed original research studies published in PubMed, Embase, the Cochrane Library, Scopus, POPLINE and the WHO regional indexes from 2000 to 2019; 36 articles were retained for full text review. We documented a higher incidence of PTB with lead and cadmium exposures. The findings for mercury and arsenic exposures were inconclusive. Metal-induced oxidative stress in the placenta, epigenetic modification, inflammation, and endocrine disruptions are the most common pathways through which heavy metals and metalloids affect placental functions leading to PTB. Most of the studies were from the high-income countries, reflecting the need for additional data from low-middle-income countries, where PTB rates are higher and prenatal exposure to metals are likely to be just as high, if not higher.

Defining hypoxaemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study.

BACKGROUND: WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude. METHODS: We prospectively enrolled well, children aged 3-35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2 as possible lower thresholds for hypoxaemia. RESULTS: Our primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2 was 98% (IQR 96%-99%), and the 2.5th, 5th and 10th percentile SpO2 was 91%, 92% and 94%. No child had a SpO2 <90%. Children 3-11 months had a lower median SpO2 (97%) than 12-23 months (98%) and 24-35 months (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959). CONCLUSION: A SpO2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the child's clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxaemia is a key next step.