Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: a systematic review, meta-analysis and meta-regression

M. Pierro, E. Villamor-Martinez, E. van Westering-Kroon, M. Alvarez-Fuente, S.H. Abman, E. Villamor*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

23 Citations (Web of Science)

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).
Original languageEnglish
Pages (from-to)268-275
Number of pages8
JournalThorax
Volume77
Issue number3
Early online date23 Jul 2021
DOIs
Publication statusPublished - Mar 2022

Keywords

  • clinical epidemiology
  • paediatric lung disaese
  • FETAL-GROWTH RESTRICTION
  • MATERNAL VASCULAR UNDERPERFUSION
  • PULMONARY-HYPERTENSION
  • NEONATAL OUTCOMES
  • PREGNANCY DISORDERS
  • SEVERE ASTHMA
  • 28TH WEEK
  • PRETERM
  • PHENOTYPES
  • INFANTS

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