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Abstract
Background Antenatal pathological conditions are key in the pathogenesis of bronchopulmonary dysplasia (BPD). Pathophysiological pathways or endotypes leading to prematurity and perinatal lung injury can be clustered into two groups: infection and dysfunctional placentation, which include hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). We conducted a systematic review of observational studies exploring the association between the dysfunctional placentation endotype and BPD.
Methods MEDLINE, Embase and Web of Science databases were searched up to February 2020 for studies reporting data on the diagnosis of HDP, IUGR or small for gestational age (SGA) and BPD risk. BPD was classified as BPD28 (supplemental oxygen on day 28), BPD36 (oxygen at 36 weeks postmenstrual age), severe BPD (≥ 30% oxygen or mechanical ventilation), BPD36/death and BPD-associated pulmonary hypertension.
Results Of 6319 studies screened, 211 (347 963 infants) were included. Meta-analysis showed an association between SGA/IUGR and BPD36 (OR 1.56, 95% CI 1.37 to 1.79), severe BPD (OR 1.82, 95% CI 1.36 to 2.29) and BPD/death (OR 1.91, 95% CI 1.55 to 2.37). Exposure to HDP was not associated with BPD but was associated with decreased odds of BPD/death (OR 0.77, 95% CI 0.64 to 0.94). Both HDP (OR 1.41, 95% CI 1.10 to 1.80) and SGA/IUGR (OR 2.37, 95% CI 1.86 to 3.02) were associated with BPD-associated pulmonary hypertension.
Conclusion When placental vascular dysfunction is accompanied by fetal growth restriction or being born SGA, it is associated with an increased risk of developing BPD and pulmonary hypertension. The placental dysfunction endotype of prematurity is strongly associated with the vascular phenotype of BPD.
Prospero registration number Review protocol was registered in PROSPERO database (ID=CRD42018086877).
- clinical epidemiology
- paediatric lung disaese
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Footnotes
MP and EV-M contributed equally.
Contributors EV conceived and designed the study with input from the other authors. MP, EV-M, EvW-K and MA-F designed and executed the literature search, screened and reviewed the search results and abstracted the data. EV designed and conducted the analysis with input from MP, EV-M and MA-F. All authors contributed to the interpretation of analysis. MP, EV-M, EvW-K, and EV made the figures and tables. EV drafted the manuscript with input from the other authors. All authors reviewed the manuscript and provided important intellectual content. EV, MP and EV-M take responsibility for the article as a whole.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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