Person:

Sheikh, Aziz

Background: Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. Methods and Findings: Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding. Conclusions: There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions. Review Registration PROSPERO CRD42013004965 Please see later in the article for the Editors' Summary

Background: The UK performs poorly relative to other economically developed countries on numerous indicators of care quality for children. The contribution of iatrogenic harm to these outcomes is unclear. As primary care is the first point of healthcare contact for most children, we sought to investigate the safety of care provided to children in this setting. Methods and Findings: We undertook a mixed methods investigation of reports of primary care patient safety incidents involving sick children from England and Wales’ National Reporting and Learning System between 1 January 2005 and 1 December 2013. Two reviewers independently selected relevant incident reports meeting prespecified criteria, and then descriptively analyzed these reports to identify the most frequent and harmful incident types. This was followed by an in-depth thematic analysis of a purposive sample of reports to understand the reasons underpinning incidents. Key candidate areas for strengthening primary care provision and reducing the risks of systems failures were then identified through multidisciplinary discussions. Of 2,191 safety incidents identified from 2,178 reports, 30% (n = 658) were harmful, including 12 deaths and 41 cases of severe harm. The children involved in these incidents had respiratory conditions (n = 387; 18%), injuries (n = 289; 13%), nonspecific signs and symptoms, e.g., fever (n = 281; 13%), and gastrointestinal or genitourinary conditions (n = 268; 12%), among others. Priority areas for improvement included safer systems for medication provision in community pharmacies; triage processes to enable effective and timely assessment, diagnosis, and referral of acutely sick children attending out-of-hours services; and enhanced communication for robust safety netting between professionals and parents. The main limitations of this study result from underreporting of safety incidents and variable data quality. Our findings therefore require further exploration in longitudinal studies utilizing case review methods. Conclusions: This study highlights opportunities to reduce iatrogenic harm and avoidable child deaths. Globally, healthcare systems with primary-care-led models of delivery must now examine their existing practices to determine the prevalence and burden of these priority safety issues, and utilize improvement methods to achieve sustainable improvements in care quality.