key: cord-0979273-827pc479
authors: Rahman, Ahmed Ehsanur; Hossain, Aniqa Tasnim; Nair, Harish; Chisti, Mohammod Jobayer; Dockrell, David; Arifeen, Shams El; Campbell, Harry
title: Prevalence of hypoxaemia in children with pneumonia in low-income and middle-income countries: a systematic review and meta-analysis
date: 2022-02-15
journal: Lancet Glob Health
DOI: 10.1016/s2214-109x(21)00586-6
sha: 8d9d3ccd6dbb058aa567da253780db05d446dfaf
doc_id: 979273
cord_uid: 827pc479

BACKGROUND: Pneumonia accounts for around 15% of all deaths of children younger than 5 years globally. Most happen in resource-constrained settings and are potentially preventable. Hypoxaemia is one of the strongest predictors of these deaths. We present an updated estimate of hypoxaemia prevalence among children with pneumonia in low-income and middle-income countries. METHODS: We conducted a systematic review using the following key concepts “children under five years of age” AND “pneumonia” AND “hypoxaemia” AND “low- and middle-income countries” by searching in 11 bibliographic databases and citation indices. We included all articles published between Nov 1, 2008, and Oct 8, 2021, based on observational studies and control arms of randomised and non-randomised controlled trials. We excluded protocol papers, articles reporting hypoxaemia prevalence based on less than 100 pneumonia cases, and articles published before 2008 from the review. Quality appraisal was done with the Joanna Briggs Institute tools. We reported pooled prevalence of hypoxaemia (SpO(2) <90%) by classification of clinical severity and by clinical settings by use of the random-effects meta-analysis models. We combined our estimate of the pooled prevalence of pneumonia with a previously published estimate of the number of children admitted to hospital due to pneumonia annually to calculate the total annual number of children admitted to hospital with hypoxaemic pneumonia. FINDINGS: We identified 2825 unique records from the databases, of which 57 studies met the eligibility criteria: 26 from Africa, 23 from Asia, five from South America, and four from multiple continents. The prevalence of hypoxaemia was 31% (95% CI 26–36; 101 775 children) among all children with WHO-classified pneumonia, 41% (33–49; 30 483 children) among those with very severe or severe pneumonia, and 8% (3–16; 2395 children) among those with non-severe pneumonia. The prevalence was much higher in studies conducted in emergency and inpatient settings than in studies conducted in outpatient settings. In 2019, we estimated that over 7 million children (95% CI 5–8 million) were admitted to hospital with hypoxaemic pneumonia. The studies included in this systematic review had high τ(2) (ie, 0·17), indicating a high level of heterogeneity between studies, and a high I(2) value (ie, 99·6%), indicating that the heterogeneity was not due to chance. This study is registered with PROSPERO, CRD42019126207. INTERPRETATION: The high prevalence of hypoxaemia among children with severe pneumonia, particularly among children who have been admitted to hospital, emphasises the importance of overall oxygen security within the health systems of low-income and middle-income countries, particularly in the context of the COVID-19 pandemic. Even among children with non-severe pneumonia that is managed in outpatient and community settings, the high prevalence emphasises the importance of rapid identification of hypoxaemia at the first point of contact and referral for appropriate oxygen therapy. FUNDING: UK National Institute for Health Research (Global Health Research Unit on Respiratory Health [RESPIRE]; 16/136/109).

"blood oxygen saturation" 5,699 12 "arterial oxygen saturation" 16,179 13 "blood gas monitoring" 3,389 14

"blood gas analysis" 38,710 15

"analysis blood gas" 23 16

SpO2 9,072 17 SPO2 9,072 18 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 ( hypoxemia ) OR ( hypoxaemia ) OR ( anoxia ) OR ( hypoxia ) OR ( oximetry ) OR ( oximeter ) OR ( oximetre ) OR ( oxymetr y ) OR ( oxymeter ) OR ( oxymetre ) OR ( "blood oxygen saturation" ) OR ( "arterial oxygen saturation" ) OR ( "blood gas monitoring" ) OR ( "blood gas analysis" ) OR ( "analysis blood gas" ) OR ( spo2 ) OR ( "acute respiratory tract infections" 13,820 30

"respiratory illness*" 38,309 31

"respiratory illnesses*" 9,267 32 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 ( pneumonia ) OR ( "severe pneumonia" ) OR ( "severe disease" ) OR ( "very severe disease" ) OR ( bronchiolitis ) OR ( "acute respiratory infection" ) OR ( ari ) OR ( "acute respiratory infections" ) OR ( "acute respiratory infections" ) OR ( "acute respiratory tract infection" ) OR ( arti ) OR ( "acute respiratory tract infections" ) OR ( "respiratory illness*" ) OR ( "respiratory illnesses*" ) (((((((((((((((((((hypoxemia) OR hypoxaemia) OR anoxia) OR hypoxia) OR oximetry) OR oximeter) OR oximetry) OR oxymetry) OR oximeter) OR oxymetry) OR blood oxygen saturation) OR arterial oxygen saturation) OR blood gas monitoring) OR blood gas analysis) OR analysis blood gas) OR SpO2) OR SPO2)) AND (((((((((((((pneumonia) Hypoxaemia (tw:(hypoxemia)) AND (instance:"ghl") 3.987 2 tw:(hypoxaemia) AND (instance:"ghl") 101 3 tw:(anoxia) AND (instance:"ghl") 4,848 4 tw:(hypoxia) AND (instance:"ghl") 9.655 5 tw:(oximetry) AND (instance:"ghl") 1.034 6 tw:(oximeter) AND (instance:"ghl") 297 7 oximetre 0 8 tw:(oxymetry) AND (instance:"ghl") 83 9

tw:(oxymeter) AND (instance:"ghl") 37 10 oxymetre 0 11 tw:(blood oxygen saturation ) AND (instance:"ghl") 2.152 12 tw:(arterial oxygen saturation) AND (instance:"ghl") 1.616 13 tw:(blood gas monitoring ) AND (instance:"ghl") 620 14 tw:(blood gas analysis ) AND (instance:"ghl") 3.715 15 tw:(analysis blood gas ) AND (instance:"ghl") 3.715 16 tw:(spo2) AND (instance:"ghl") 1.095 17 tw:(spo2) AND (instance:"ghl") 1.095 18 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 tw:(hypoxemia OR hypoxaemia OR anoxia OR hypoxia OR oximetry OR oximeter OR oximetre OR oxymetry OR 18,269 oxymeter OR oxymetre OR (blood oxygen saturation) OR (arterial oxygen saturation) OR (blood gas monitoring) OR (blood gas analysis) OR (analysis blood gas) OR spo2 OR spo2) AND (instance:"ghl") 19

Pneumonia tw:(pneumonia) AND ( The previous IMCI guidelines (published in 2008) recommend that any child presenting with cough or difficult breathing should be assessed clinically for the presence of any danger sign, chest in-drawing, stridor, wheezing; and would be classified as one of the followings (Error! Reference source not found.):1.

'Severe Pneumonia/Very Severe Disease' ; 2. 'Pneumonia', 3. 'Cough or Cold'

The sensitivity of the previous definition of 'Severe Pneumonia/Very Severe Disease' was very high but it had issues with low specificity. This resulted in over referral of 'Severe Pneumonia/Very Severe Disease'

cases to the hospital for inpatient care. As a results, it was imperative to reassess the validity of 'severe pneumonia' classification as outlined in the previous IMCI guidelines (2008). Prognostic value and treatment options for different signs of 'severe pneumonia' including chest in-drawing required a critical evaluation.

The new IMCI guidelines (2014) recommends that any child (2 months to 59 months) presenting with fast breathing or chest in-drawing (and no other danger signs) should be classified as 'Pneumonia', and would be treated through home-based management with oral antibiotics (amoxicillin for five days). In addition to other changes in the management to malnutrition, this was the most significant shift from the previous classification and treatment recommendation for pneumonia management. Previously, any child with chest indrawing would be classified as 'Severe Pneumonia', therefore would have been urgently referred to the hospital. Figure 1 .

Supplementary Figure 7: Hypoxaemia prevalence among WHO-classified pneumonia by Patient Status*

 (2008 vs. 2014 ) (adopted from the WHO evidence summary) † Not able to drink, persistent vomiting, convulsions, lethargic or unconscious, stridor in a calm child or severe malnutrition.