Placental Pathologic Changes of Maternal Vascular Underperfusion in Bronchopulmonary Dysplasia and Pulmonary Hypertension

Placenta. 2014 Aug;35(8):570-4. doi: 10.1016/j.placenta.2014.05.003. Epub 2014 May 20.


Introduction: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH.

Methods: We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates.

Results: Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P < 0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P < 0.001).

Discussion: Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease.

Conclusions: Our findings have important implications for providing earlier and more effective therapies for BPD.

Keywords: Bronchopulmonary dysplasia; Fetal growth restriction; Placenta; Preeclampsia; Premature infant; Pulmonary hypertension.

MeSH terms

  • Bronchopulmonary Dysplasia / etiology*
  • Bronchopulmonary Dysplasia / pathology
  • Female
  • Humans
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / pathology
  • Infant, Extremely Premature
  • Infant, Newborn
  • Logistic Models
  • Male
  • Placenta / blood supply*
  • Placenta / pathology
  • Pregnancy
  • Retrospective Studies