Placental Villous Vascularity is Decreased in Premature Infants with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension

Abstract

The development of pulmonary hypertension (PH) is a serious complication of bronchopulmonary dysplasia (BPD) among infants born at extremely low gestational ages. Bronchopulmonary dysplasia-associated PH is characterized by persistent pulmonary vasoconstriction, progressive right heart dysfunction, and an increased risk of death. We have shown previously that certain placental vascular lesions are associated with BPD-associated PH. Further evaluation of the villous and vascular morphometry of these placentas is warranted. Using digital image analysis (DIA), we compared villous and vascular morphometric parameters of placentas from infants with and without BPD-associated PH. We conducted a case-control study of placentas from 14 infants born at ≤28 weeks' gestational age (GA). Cases with PH (N=7) and non-PH controls (N=7) were identified using echocardiogram screening at 36 weeks' corrected GA. Central parenchymal sections from each placenta were stained for CD31. Digital image analysis was used to measure vessel and villous capillary number, perimeter, diameter, and area. Mean villous vascularity (number of vessels per villus) was calculated for each patient. Mean vessel and villous number as well as area were similar between the two groups. Villous vascularity was decreased in placentas from infants who ultimately had PH disease compared to non-PH controls (5.5±1.0 vs 7.1±1.6; P<0.05). Placental villous vascularity is decreased in infants with BPD-associated PH. Further studies should assess whether placental morphometric markers may allow clinicians to better predict BPD and provide earlier and more targeted management.

Cord Blood Biomarkers of Placental Maternal Vascular Underperfusion Predict Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension

“…The distinctions between vascular and inflammatory processes in placenta and cord blood suggest that BPD-PH arises from a pathophysiology that is different from BPD alone. This concept is demonstrated in our previous placental studies, 5,29 and further illustrated in the cord blood biomarker profiles of BPD only versus BPD-PH shown in the Figure.…”

“…5 More recently, we conducted immunohistochemical staining of trophoblast vessels and found decreased villous vascularity in placentas of infants with BPD-PH, providing morphometric evidence that early delayed placental angiogenesis mirrors future pulmonary vascular disease. 29 The underlying mechanisms remain unclear. Investigation of cord blood delineates the profile of biochemical factors circulating at the time of birth, and provides insight into the interplay between placental and pulmonary vascular dysfunction in the developing premature infant lung.…”

Identification of gaps in the current knowledge on pulmonary hypertension in extremely preterm infants: A systematic review and meta‐analysis

“…We included two articles by scanning the reference lists. Finally, 25 articles, 16 retrospective and 9 prospective studies, were eligible for inclusion in the study . The flow chart of this excluding process is given in Figure .…”

“…Eight studies that were included provided clearly defined objectives, study populations, and outcome measures . However, 17 of the 25 included studies had a retrospective design and included a selected study population . Four studies reported on a study population of extremely preterm infants with and without BPD, whereas 16 studies reported selectively on infants with BPD and seven studies reported selectively on a study population of infants with moderate/severe BPD .…”

“…A substantial variety of PH prevalences was reported for these infants, ranging from 0%‐10% . Only 9 of 25 studies reported on PH in extremely preterm infants with BPD bus also in those without BPD, while the other 16 studies focused exclusively on PH in infants with BPD . Moreover, 2 of 9 studies on infants both with and without BPD, selectively only reported characteristics of the infants with BPD .…”