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Bronchopulmonary dysplasia-associated pulmonary hypertension: clues from placental pathology

Journal of Perinatology volume 37, pages 1310–1314 (2017)Cite this article

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Abstract

Objectives:

Bronchopulmonary dysplasia (BPD) and the associated complication of pulmonary hypertension (PH) leads to increased mortality and a longer length of stay among survivors. Placental histopathology may give early clues of subsequent events. The objective was to evaluate the relationship of maternal vascular underperfusion (MVU) changes on placental histopathology with subsequent development of BPD-associated PH in a cohort of extremely premature infants.

Study Design:

In a cohort of preterm infants ‘⩽28 weeks’ gestational age (GA) and with ‘severe’ BPD, this retrospective study evaluated specific placental histopathological changes and assessed the relationship with subsequent development of PH. ‘Severe’ BPD was defined as the need for ⩾30% oxygen and/or positive pressure ventilation at 36 weeks postmenstrual age. Placental and echocardiographic assessments were done by investigators masked to the grouping and clinical outcomes.

Results:

Fifty six infants with severe BPD formed the cohort; PH was noted in 22 (39.3%) infants. The GA of the infants with and without PH was comparable (25.8±1.6 vs 25.8±1.3 weeks, P=0.9). On placental histopathological examination, 13 (23%) had features of MVU. On univariate logistic regression, the presence of changes consistent with MVU increased the relative risk of subsequent BPD-associated PH by 2.75 (95% confidence interval 1.56 to 4.85, P=0.004). The significance persisted after adjustment for GA. Stratification by the presence or absence of fetal growth restriction, yielded nonsignificant associations (P=0.17).

Conclusion:

Based on the results of the present study, specific placental histopathological changes may give early clues to the subsequent development of BPD-associated PH.

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References

  1. Mourani PM, Mullen M, Abman SH . Pulmonary hypertension in bronchopulmonary dysplasia. Prog Pediatr Cardiol 2009; 27: 43–48.

    Article  Google Scholar 

  2. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126: 443–456.

    Article  Google Scholar 

  3. Chow SSW, Le Marsney R, Haslam R, Lui K . Report of the Australia and New Zealand Neonatal Network 2014. 2016.

  4. An HS, Bae EJ, Kim GB, Kwon BS, Beak JS, Kim EK et al. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Korean Circ J 2010; 40: 131–136.

    Article  Google Scholar 

  5. Bhat R, Salas AA, Foster C, Carlo WA, Ambalavanan N . Prospective analysis of pulmonary hypertension in extremely low birth weight infants. Pediatrics 2012; 129: e682–e689.

    Article  Google Scholar 

  6. Fouron JC, Le Guennec JC, Villemant D, Perreault G, Davignon A . Value of echocardiography in assessing the outcome of bronchopulmonary dysplasia of the newborn. Pediatrics 1980; 65: 529–535.

    CAS  PubMed  Google Scholar 

  7. Revanna GK, Kunjunju A, Sehgal A . Bronchopulmonary dysplasia associated pulmonary hypertension: making the best use of bedside echocardiography. J Pediatr 2017; 185: 33–41.

    Article  Google Scholar 

  8. Kim GB . Pulmonary hypertension in infants with bronchopulmonary dysplasia. Korean J Pediatr 2010; 53: 688–693.

    Article  Google Scholar 

  9. Bose C, Van Marter LJ, Laughon M, O’Shea TM, Allred EN, Karna P et al. Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation. Pediatrics 2009; 124: e450–e458.

    Article  Google Scholar 

  10. Check J, Gotteiner N, Liu X, Su E, Porta N, Steinhorn R et al. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia. J Perinatol 2013; 33: 553e7.

    Article  Google Scholar 

  11. Ozkan H, Cetinkaya M, Koksal N . Increased incidence of bronchopulmonary dysplasia in preterm infants exposed to preeclampsia. J Matern Fetal Neonatal Med 2012; 25: 2681e5.

    Article  Google Scholar 

  12. Mourani PM, Abman SH . Pulmonary vascular disease in bronchopulmonary dysplasia: pulmonary hypertension and beyond. Curr Opin Pediatr 2013; 25: 329–337.

    Article  CAS  Google Scholar 

  13. Rozance PJ, Seedorf GJ, Brown A, Roe G, O’Meara MC, Gien J et al. Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep. AJP Lung Cell Mol Physiol 2011; 301: L860–L871.

    Article  CAS  Google Scholar 

  14. Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS . Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938–941.

    Article  CAS  Google Scholar 

  15. Mestan KK, Check J, Minturn L, Yallapragada S, Farrow KN, Liu X et al. Placental pathologic changes of maternal vascular under perfusion in bronchopulmonary dysplasia and pulmonary hypertension. Placenta 2014; 35: 570–574.

    Article  CAS  Google Scholar 

  16. Jobe AH, Bancalari E . Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723–1729.

    Article  CAS  Google Scholar 

  17. Lau EM, Manes A, Celermajer DS, Galiè N . Early detection of pulmonary vascular disease in pulmonary arterial hypertension: time to move forward. Eur Heart J 2011; 32: 2489–2498.

    Article  Google Scholar 

  18. Nagiub M, Lee S, Guglani L . Echocardiographic assessment of pulmonary hypertension in infants with bronchopulmonary dysplasia: Systematic review of literature and a proposed algorithm for assessment. Echocardiography 2015; 32: 819–833.

    Article  Google Scholar 

  19. King ME, Braun H, Goldblatt A, Liberthson R, Weyman AE . Interventricular septal configuration as a predictor of right ventricular systolic hypertension in children: a cross-sectional echocardiographic study. Circulation 1983; 68: 68–75.

    Article  CAS  Google Scholar 

  20. Musewe NN, Poppe D, Smallhorn JF . Doppler echocardiographic measurement of pulmonary artery pressure from ductal Doppler velocities in the newborn. J Am Coll Cardiol 1990; 15: 446–456.

    Article  CAS  Google Scholar 

  21. Abraham S, Weismann CG . Left ventricular end-systolic eccentricity index for assessment of pulmonary hypertension in infants. Echocardiography 2016; 33: 910–915.

    Article  Google Scholar 

  22. Pande A, Sarkar A, Ahmed I, Naveen Chandra G, Patil SK, Kundu CK et al. Non-invasive estimation of pulmonary vascular resistance in patients of pulmonary hypertension in congenital heart disease with unobstructed pulmonary flow. Ann Pediatr Cardiol 2014; 7: 92–97.

    Article  Google Scholar 

  23. Redline RW, Boyd T, Campbell V, Hyde S, Kaplan C, Khong TY et al. Maternal vascular under-perfusion: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 2004; 7: 237–249.

    PubMed  Google Scholar 

  24. Khemani E, McElhinney DB, Rhein L, Andraade O, Lacro RV, Thomas KC et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 2007; 120: 1260–1269.

    Article  Google Scholar 

  25. Kim D-H, Kim H-S, Choi CW, Kim E-K, Kim BI, Choi J-H . Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology 2012; 101: 40–46.

    Article  Google Scholar 

  26. Mestan KK, Gotteiner N, Porta N, Grobman W, Su EJ, Ernst LM . Cord blood biomarkers of placental maternal vascular underperfusion predict bronchopulmonary dysplasia-associated pulmonary hypertension. J Pediatr 2017; 185: 33–46 pii: S0022-S3476(17)30033-1.

    Article  CAS  Google Scholar 

  27. Sehgal A, Malikiwi A, Paul E, Tan K, Menahem S . Systemic arterial stiffness in infants with bronchopulmonary dysplasia: potential cause of systemic hypertension. J Perinatol 2016; 36: 564–569.

    Article  CAS  Google Scholar 

  28. Gan CTJ, Lankhaar JW, Westerhof N, Marcus JT, Becker A, Twisk JWR et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest 2007; 132: 1906–1912.

    Article  Google Scholar 

  29. Wang Z, Chesler N . Pulmonary vascular wall stiffness: an important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulm Circ 2011; 1: 212–223.

    Article  Google Scholar 

  30. Mukherjee D . Atherogenic vascular stiffness and hypertension cause or effect? JAMA 2012; 308: 919–920.

    Article  CAS  Google Scholar 

  31. Willard JEL, Richard A, Hillis LD Cardiac catheterization. In: Kloner RA. The Guide to Cardiology, 3rd edn. Le Jacq Communications: Greenwich, CT, 1995; 151.

    Google Scholar 

  32. Shrout PE, Fleiss JL . Intraclass correlations: uses in assessing rater reliability. Psychol Bull 1979; 86: 420–428.

    Article  CAS  Google Scholar 

  33. Yock PG, Popp RL . Non-invasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984; 70: 657–662.

    Article  CAS  Google Scholar 

  34. Abbas AE, Fortuin FD, Schiller NB, Appleton CP, Moreno CA, Lester SJ . A simple method for non-invasive estimation of pulmonary vascular resistance. J Am Coll Cardiol 2003; 41: 1021–1027.

    Article  Google Scholar 

  35. Ajami GH, Cheriki S, Amoozgar H, Borzouee M, Soltani M . Accuracy of Doppler-derived estimation of pulmonary vascular resistance in congenital heart disease: an index of operability. Pediatr Cardiol 2011; 32: 1168–1174.

    Article  Google Scholar 

  36. Vlahos AP, Feinstein JA, Schiller NB, Silverman NH . Extension of Doppler-derived echocardiographic measures of pulmonary vascular resistance to patients with moderate or severe pulmonary vascular disease. J Am Soc Echocardiogr 2008; 21: 711–714.

    Article  Google Scholar 

  37. Howard LS, Grapsa J, Dawson D, Bellamy M, Chambers JB, Masani ND et al. Echocardiographic assessment of pulmonary hypertension: standard operating procedure. Eur Respir Rev 2012; 21: 239–248.

    Article  Google Scholar 

  38. Lal CV, Ambalavanan N . Biomarkers, early diagnosis, and clinical predictors of BPD. Clin Perinatol 2015; 42: 739–754.

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Monash Newborn, Monash University Neonatologist, Monash Children’s Hospital, Melbourne, VIC, Australia

    A M Kunjunju, K R Gopagondanahalli & A Sehgal

  2. Department of Pathology, Monash Health, Melbourne, VIC, Australia

    Y Chan

  3. Department of Pediatrics, Monash University, Melbourne, Australia

    A Sehgal

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  1. A M Kunjunju
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Correspondence to A Sehgal.

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Kunjunju, A., Gopagondanahalli, K., Chan, Y. et al. Bronchopulmonary dysplasia-associated pulmonary hypertension: clues from placental pathology. J Perinatol 37, 1310–1314 (2017). https://doi.org/10.1038/jp.2017.130

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