Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension

Abstract

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.

Fetal Doppler velocimetry and bronchopulmonary dysplasia risk among growth-restricted preterm infants: an observational study

“…10 Placenta acts as the director of the whole fetal development and its pathology has already been associated with lung and vascular disease in the offspring: Mestan et al have shown that maternal placental vascular underperfusion is associated with the development of BPD among preterm infants. 11 Fetal Doppler examination enables clinicians to identify placental underperfusion and the resulting adverse fetal environment. Experimental sheep FGR models have highlighted impaired lung function and structure as well as endothelial dysfunction in growth-restricted offspring suggesting that placental insufficiency may impair both pulmonary angiogenesis and alveolarisation.…”

“…Data about prenatal and neonatal characteristics were prospectively collected in the obstetric medical record and Neonatal Unit database, respectively. FGR diagnosis was based on the coexistence of failing fetal growth in utero, defined as the reduction of the estimated fetal weight of at least 1 SD in two ultrasound scans within 2 weeks and fetal Doppler velocimetry abnormalities, defined as the presence of one of the following conditions: 11 ► umbilical artery pulsatility index (PI) greater than the 95th centile, ► absent or reversed end diastolic flow velocities on at least 50% of the Doppler waveforms from the umbilical artery on at least one occasion during pregnancy, ► cerebral redistribution, defined as occurring when both the umbilical artery PI is greater than the 95th centile and the middle cerebral artery PI is less than the 5th centile for GA.…”

“…Up to now, several studies have suggested an association between placental disorders affecting fetal wellness and BPD. [8][9][10][11] Aim of this study was to evaluate whether FGR diagnosis, based on pathological prenatal fetal Doppler velocimetry, is Fetal Doppler velocimetry and bronchopulmonary dysplasia risk among growth-restricted preterm infants: an observational study Alessandra Lio, 1 Paolo Rosati, 2 Roberta Pastorino, 3 Francesco Cota, 1 Milena Tana, 1 Chiara Tirone, 1 Claudia Aurilia, 1 Cinzia Ricci, 1 Alessandro Gambacorta, 1 Angela Paladini, 1 Ilenia Mappa, 2 Silvia Buongiorno, 2 Gian Franco Zannoni, 4 Costantino Romagnoli, 1 ► This is one of the first studies defining fetal growth restriction as the coexistence of failing of fetal growth and abnormal fetal Doppler velocimetry rather than just a low birth weight (BW). ► We reported that small for gestational age preterm infants have the highest bronchopulmonary dysplasia (BPD) risk when placenta dysfunction is the surrounding cause of low BW.…”

The Influence of Pregnancy Disorders Causing Preterm Delivery on In-Hospital Outcomes in Preterm Infants at Less than 32 Weeks of Gestation

“…28 Recently, there have been some reports that placental pathologic changes of maternal vascular underperfusion in BPD are associated with increased risk of pulmonary hyper tension, 29 and after a systematic review and metaanalysis, oligohydramnios and SGA were shown as significant risk fac tors of pulmonary hypertension in infants with BPD. 30 Addi tionally, in our study, SGAP was a significant risk factor of pulmonary hypertension.…”

Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK

“…Although PH predominantly develops in the very low birth weight and very preterm infant, some infants develop late onset PH after a couple of weeks 22 36 37. Furthermore, the moderate but growth-retarded preterm infant has been shown to develop PH in a considerable number of cases 36.…”