Elsevier

Placenta

Volume 35, Issue 8, August 2014, Pages 570-574
Placenta

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

https://doi.org/10.1016/j.placenta.2014.05.003Get rights and content

Highlights

  • We conducted a 5-year retrospective cohort study of extremely premature infants.

  • Placental MVU was increased among infants who develop BPD.

  • Fibrinoid necrosis and distal villous hypoplasia were further increased with PH.

  • In clinical settings, MVU may help predict development of BPD and BPD-associated PH.

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.

Introduction

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, affecting one-half of extremely premature infants (born ≤28 weeks). BPD-associated pulmonary hypertension (PH) is an increasingly recognized pulmonary vascular problem in over one-third of BPD infants, characterized by persistently elevated pulmonary arterial pressures, chronic hypoxia, cardiopulmonary instability, right heart dysfunction, and early childhood death [1], [2]. The severity of BPD and presence of PH disease are often not apparent until several weeks to months after birth. Early, accessible biological markers that delineate the fetal pathophysiology of an individual infants' lung disease may be helpful in guiding the neonatal management of premature infants, so that BPD may be minimized or prevented. Despite extensive research, such markers have not yet been identified.

Placental pathologic findings related to preeclampsia and fetal growth restriction (FGR) may serve as promising early predictors of BPD and PH. This is because chronic vascular malperfusion of the placental bed during fetal development may lead to pulmonary vascular remodeling, the hallmark of PH disease and to a lesser extent a proposed mechanism of BPD. Maternal vascular underperfusion (MVU) of the placental bed is perhaps best understood as a marker of preeclampsia, and has been shown to negatively impact the fetus as it is a prominent lesion in FGR [3]. Preeclampsia and FGR are also risk factors for BPD and PH [4], [5], [6], although not reliably present in all cases given the multifactorial nature of these diseases. Moreover, not all cases of MVU are accompanied by clinically apparent preeclampsia or FGR, especially in cases of extremely preterm birth since delivery of the fetus may occur before maternal signs are manifest. Therefore, an important question is whether MVU could serve as an independent earlier predictor of BPD and PH.

The objectives of this study were, firstly, to evaluate the association between placental MVU and BPD among infants born ≤28 weeks gestational age (GA), and secondly, to further investigate the association between MVU and BPD-associated PH. We hypothesized that the presence of MVU is predictive of BPD, and most prominent among BPD infants who develop PH at 36 weeks corrected age (CA).

Section snippets

Study design and patients

We conducted a five-year retrospective cohort study at Northwestern Prentice Women's Hospital, in which all infants born ≤28 completed weeks (GA range 230/7 to 286/7 weeks) between January 2005 and December 2009 were identified. Standardized chart reviews were performed. Archived placental pathology slides from each delivery were retrieved and reviewed by a single perinatal pathologist using a standardized algorithm (see below). All infants who were inborn at Prentice and for whom placental

Results

A total of 330 infants ≤28 weeks GA were inborn and admitted at Prentice between January 1, 2005 and December 31, 2009. Of this group, 37 had incomplete reports for the following reasons: 27 had missing slides or incomplete maternal record information necessary to locate the appropriate slides, and 10 births had placental tissues available but could not be designated due to multiple gestation status or mislabeling. Therefore, a total of 293 mother–infant pairs with complete placental data were

Discussion

We found that placental MVU is associated with the development of BPD among extremely premature infants. When taking into account maternal, infant, and other placental histologic covariates, the MVU on BPD association was robust. MVU also appeared to be more strongly associated with BPD as compared to other major neonatal outcomes. Lastly, certain MVU sublesions were particularly prominent among BPD infants who developed PH disease. Our findings support the role for placental vascular markers

Funding sources

This project was supported by NHLBI Grant K23 HL093302 (PI: Mestan), and the Northwestern Memorial Foundation Friends of Prentice Grants Initiative (PI: Mestan).

Contributors

Karen K. Mestan: Dr. Mestan conceptualized and designed the study, prepared the results, drafted the initial manuscript, and approved the final manuscript as submitted.

Jennifer Check: Dr. Check designed and implemented the data collection and data management procedures for clinical, placental and echocardiogram data.

Lucy Minturn: Ms. Minturn designed and implemented the data collection, entry, and management procedures for placental pathology data.

Sushmita Yallapragada: Dr. Yallapragada

Conflict of interest

Each of the above authors attests that there are no conflicts of interest to disclose.

Acknowledgments

We thank neonatology fellow Dr. Stephannie Baehl-Voller for her assistance with the medical record review and clinical data collection for this study.

References (22)

  • American College of Obstetricians and Gynecologists

    ACOG Practice Bulletin No. 101: ultrasonography in pregnancy

    Obstet Gynecol

    (2009)
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