Skip to main content

Advertisement

Log in

Vascular placental pathology and the relationship between hypertensive disorders of pregnancy and neonatal outcomes in very low birth weight infants

  • Article
  • Published:
Journal of Perinatology Submit manuscript

Abstract

Objective:

To investigate vascular placental pathology’s effect on known associations between hypertensive disorders and four adverse neonatal outcomes—bronchopulmonary dysplasia, intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and death.

Study Design:

Retrospective cohort of very low birth weight neonates born at a single center (n = 911). Statistical analysis included χ2, t test, modified Poisson regression with robust error variance to measure risk, and Wald test. Stratified models assessed the effect of maternal hypertension on neonatal outcomes in those exposed to placental pathology.

Results:

Neonates exposed to maternal hypertension and placental pathology had an increased risk of bronchopulmonary dysplasia (relative risk (RR) = 5.23, 95% confidence interval (CI): 2.07, 13.22) compared to those exposed to hypertension without placental pathology (RR = 1.63, 95% CI: 1.14, 2.34; Wald test p = 0.02). Similar, but non-significant, trends also emerged for necrotizing enterocolitis and death.

Conclusion:

Vascular placental pathology may amplify the risk of adverse outcomes in neonates exposed to hypertension and may mark the extent to which hypertension affects neonates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. 2013:1-88.

  2. Afjeh SA, Sabzehei MK, Fallahi M, Esmaili F. Outcome of very low birth weight infants over 3 years report from an Iranian center. Iran J Pediatr. 2013;23:579–87.

    PubMed  PubMed Central  Google Scholar 

  3. Redline RW, Wilson-Costello D, Hack M. Placental and other perinatal risk factors for chronic lung disease in very low birth weight infants. Pediatr Res. 2002;52:713–9.

    Article  PubMed  Google Scholar 

  4. Torchin H, Ancel PY, Goffinet F, Hascoet JM, Truffert P, Tran D, et al. Placental complications and bronchopulmonary dysplasia: EPIPAGE-2 Cohort Study. Pediatrics. 2016;137:e20152163.

  5. Hansen AR, Barnes CM, Folkman J, McElrath TF. Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. J Pediatr. 2010;156:532–6.

    Article  PubMed  Google Scholar 

  6. Kim CR, Vohr BR, Oh W. Effects of maternal hypertension in very-low-birth-weight infants. Arch Pediatr Adolesc Med. 1996;150:686–91.

    Article  PubMed  CAS  Google Scholar 

  7. Bashiri A, Zmora E, Sheiner E, Hershkovitz R, Shoham-Vardi I, Mazor M. Maternal hypertensive disorders are an independent risk factor for the development of necrotizing enterocolitis in very low birth weight infants. Fetal Diagn Ther. 2003;18:404–7.

    Article  PubMed  Google Scholar 

  8. Chen XK, Wen SW, Smith G, Yang Q, Walker M. Pregnancy-induced hypertension is associated with lower infant mortality in preterm singletons. BJOG. 2006;113:544–51.

    Article  PubMed  CAS  Google Scholar 

  9. Perlman JM, Risser RC, Gee JB. Pregnancy-induced hypertension and reduced intraventricular hemorrhage in preterm infants. Pediatr Neurol. 1997;17:29–33.

    Article  PubMed  CAS  Google Scholar 

  10. Yen TA, Yang HI, Hsieh WS, Chou HC, Chen CY, Tsou KI, et al. Preeclampsia and the risk of bronchopulmonary dysplasia in VLBW infants: a population based study. PLoS ONE. 2013;8:e75168.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. O’Shea JE, Davis PG, Doyle LW, Victorian Infant Collaborative Study Group. Maternal preeclampsia and risk of bronchopulmonary dysplasia in preterm infants. Pediatr Res. 2012;71:210–4.

    Article  PubMed  Google Scholar 

  12. Akram Khan M, Kuzma-O’Reilly B, Brodsky NL, Bhandari V. Site-specific characteristics of infants developing bronchopulmonary dysplasia. J Perinatol. 2006;26:428–35.

    Article  PubMed  CAS  Google Scholar 

  13. March MI, Gupta M, Modest AM, Wu L, Hacker MR, Martin CR, et al. Maternal risk factors for neonatal necrotizing enterocolitis. J Matern Fetal Neonatal Med. 2014;28:1285–90.

    Article  Google Scholar 

  14. Cetinkaya M, Ozkan H, Koksal N, Karali Z, Ozgur T. Neonatal outcomes of premature infants born to preeclamptic mothers. J Matern Fetal Neonatal Med. 2010;23:425–30.

    Article  PubMed  Google Scholar 

  15. Luig M, Lui K, NSW & ACT NICUS Group. Epidemiology of necrotizing enterocolitis—Part II: risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005;41:174–9.

    Article  PubMed  Google Scholar 

  16. Wolf EJ, Vintzileos AM, Rosenkrantz TS, Rodis JF, Salafia CM, Pezzullo JG. Do survival and morbidity of very-low-birth-weight infants vary according to the primary pregnancy complication that results in preterm delivery? Am J Obstet Gynecol. 1993;169:1233–9.

    Article  PubMed  CAS  Google Scholar 

  17. Ogunyemi D, Murillo M, Jackson U, Hunter N, Alperson B. The relationship between placental histopathology findings and perinatal outcome in preterm infants. J Matern Fetal Neonatal Med. 2003;13:102–9.

    Article  PubMed  CAS  Google Scholar 

  18. Salafia CM, Pezzullo JC, Lopez-Zeno JA, Simmens S, Minior VK, Vintzileos AM. Placental pathologic features of preterm preeclampsia. Am J Obstet Gynecol. 1995;173:1097–105.

    Article  PubMed  CAS  Google Scholar 

  19. Kovo M, Schreiber L, Ben-Haroush A, Wand S, Golan A, Bar J. Placental vascular lesion differences in pregnancy-induced hypertension and normotensive fetal growth restriction. Am J Obstet Gynecol. 2010;202:561.e1–561.e5.

    Article  Google Scholar 

  20. Mestan KK, Check J, Minturn L, Yallapragada S, Farrow KN, Liu X, et al. Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension. Placenta. 2014;35:570–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Moore SW, Arnold M, Wright C. Necrotizing enterocolitis and the placenta—a key etiological link. J Pediatr Surg. 2013;48:359–62.

    Article  PubMed  Google Scholar 

  22. 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  PubMed  PubMed Central  Google Scholar 

  23. Zook KJ, Mackley AB, Kern J, Paul DA. Hematologic effects of placental pathology on very low birthweight infants born to mothers with preeclampsia. J Perinatol. 2009;29:8–12.

    Article  PubMed  CAS  Google Scholar 

  24. de Jongh BE, Mackley A, Jain N, Locke R, Paul DA. Effects of advanced maternal age and race/ethnicity on placental weight and placental weight/birthweight ratio in very low birthweight infants. Matern Child Health J. 2015;19:1553–8.

    Article  PubMed  Google Scholar 

  25. American College of Obstetricians and Gynecologists Committee on Obstetric Practice. Diagnosis and Management of Preeclampsia and Eclampsia. ACOG Practice Bulletin No 33. Obstet Gynecol. 2002;99:159–67.

    Article  Google Scholar 

  26. Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, et al. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005;116:1353–60.

    Article  PubMed  Google Scholar 

  27. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.

    Article  PubMed  CAS  Google Scholar 

  28. Kusters CD, Chen ML, Follett PL, Dammann O. “Intraventricular” hemorrhage and cystic periventricular leukomalacia in preterm infants: how are they related? J Child Neurol. 2009;24:1158–70.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Langston C, Kaplan C, Macpherson T, Manci E, Peevy K, Clark B, et al. Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists. Arch Pathol Lab Med. 1997;121:449–76.

    PubMed  CAS  Google Scholar 

  30. Redline RW, Boyd T, Campbell V, Hyde S, Kaplan C, Khong TY, et al. Maternal vascular underperfusion: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol. 2004;7:237–49.

    PubMed  Google Scholar 

  31. Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159:702–6.

    Article  PubMed  Google Scholar 

  32. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 3rd ed. Philadelphia, PA: Lippincort, Williams & Wilkins; 2008.

    Google Scholar 

  33. Abman SH. Bronchopulmonary dysplasia: “a vascular hypothesis”. Am J Respir Crit Care Med. 2001;164:1755–6.

    Article  PubMed  CAS  Google Scholar 

  34. Thebaud B, Abman SH. Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med. 2007;175:978–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Tang JR, Karumanchi SA, Seedorf G, Markham N, Abman SH. Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 2012;302:L36–46.

    Article  PubMed  CAS  Google Scholar 

  36. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364:255–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Shah DM. Perinatal implications of maternal hypertension. Semin Pediatr Neurol. 2001;8:108–19.

    Article  PubMed  CAS  Google Scholar 

  38. Nowicki PT. Ischemia and necrotizing enterocolitis: where, when, and how. Semin Pediatr Surg. 2005;14:152–8.

    Article  PubMed  Google Scholar 

  39. Huppertz B. Placental pathology in pregnancy complications. Thromb Res. 2011;127 Suppl 3:S96–99.

    Article  PubMed  Google Scholar 

  40. Korteweg FJ, Erwich JJ, Holm JP, Ravise JM, van der Meer J, Veeger NJ, et al. Diverse placental pathologies as the main causes of fetal death. Obstet Gynecol. 2009;114:809–17.

    Article  PubMed  Google Scholar 

  41. Horn LC, Langner A, Stiehl P, Wittekind C, Faber R. Identification of the causes of intrauterine death during 310 consecutive autopsies. Eur J Obstet Gynecol Reprod Biol. 2004;113:134–8.

    Article  PubMed  Google Scholar 

  42. Kidron D, Bernheim J, Aviram R. Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation. Placenta. 2009;30:700–4.

    Article  PubMed  CAS  Google Scholar 

  43. Roescher AM, Timmer A, Erwich JJ, Bos AF. Placental pathology, perinatal death, neonatal outcome, and neurological development: a systematic review. PLoS ONE. 2014;9:e89419.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Goland RS, Tropper PJ, Warren WB, Stark RI, Jozak SM, Conwell IM. Concentrations of corticotrophin-releasing hormone in the umbilical-cord blood of pregnancies complicated by pre-eclampsia. Reprod Fertil Dev. 1995;7:1227–30.

    Article  PubMed  CAS  Google Scholar 

  45. Goland RS, Jozak S, Warren WB, Conwell IM, Stark RI, Tropper PJ. Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses. J Clin Endocrinol Metab. 1993;77:1174–9.

    PubMed  CAS  Google Scholar 

  46. Vergani P, Patane L, Doria P, Borroni C, Cappellini A, Pezzullo JC, et al. Risk factors for neonatal intraventricular haemorrhage in spontaneous prematurity at 32 weeks gestation or less. Placenta. 2000;21:402–7.

    Article  PubMed  CAS  Google Scholar 

  47. Gagliardi L, Rusconi F, Da Fre M, Mello G, Carnielli V, Di Lallo D, et al. Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study. Pediatr Res. 2013;73:794–801.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lisa Strouss.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strouss, L., Goldstein, N.D., Locke, R. et al. Vascular placental pathology and the relationship between hypertensive disorders of pregnancy and neonatal outcomes in very low birth weight infants. J Perinatol 38, 324–331 (2018). https://doi.org/10.1038/s41372-017-0032-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-017-0032-4

  • Springer Nature America, Inc.

This article is cited by

Navigation