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Published on: August 7, 2017
Preterm birth and childhood wheezing disorders: a systematic review and meta-analysis
Jasper V Been1, Marlies J Lugtenberg2, Eline Smets2
1Department of Paediatrics, Maastricht University Medical Centre, Maastricht, Netherlands ; School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Netherlands ; Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Insights
Preterm birth significantly increases the risk of childhood asthma and wheezing disorders, especially for very preterm infants. Further research is needed to understand mechanisms and develop preventive strategies.
Area of Science:
- Pediatric respiratory health
- Epidemiology of non-communicable diseases
- Neonatal care outcomes
Background:
- Early life factors are increasingly linked to non-communicable diseases.
- Asthma and wheezing disorders are significant childhood health concerns.
- Advances in neonatal care have increased survival rates for very preterm infants.
Purpose of the Study:
- To systematically review the association between preterm birth and asthma/wheezing disorders in children.
- To evaluate the risk of asthma/wheezing in children born preterm, including very preterm births.
- To synthesize evidence from epidemiological studies on this topic.
Main Methods:
- Systematic review of 7 online databases (1995-2013) and supplementary searches.
- Inclusion of 30 unique studies involving over 1.5 million children.
- Meta-analysis of unadjusted and adjusted effect estimates, with subgroup and sensitivity analyses.
Main Results:
- Preterm birth is associated with a significantly increased risk of wheezing disorders (OR 1.46).
- The risk is substantially higher for very preterm birth (<32 weeks gestation; OR 2.81).
- Population-attributable risk for childhood wheezing disorders due to preterm birth is estimated at ≥3.1%.
Conclusions:
- Compelling evidence links preterm birth, particularly very preterm birth, to increased asthma risk.
- Future research should focus on underlying mechanisms and developing preventive interventions.
- Understanding these links is crucial given the rising number of preterm survivors.
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.
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