Home Medicine Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy – an 11-year single-center experience
Article
Licensed
Unlicensed Requires Authentication

Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy – an 11-year single-center experience

  • Laura D. Benz , Peter K. Bode , Simone Brandt , Beate Grass ORCID logo , Cornelia Hagmann , Rabia Liamlahi , Bernhard Frey , Ulrike Held and Barbara Brotschi EMAIL logo
Published/Copyright: October 21, 2021
Journal of Perinatal Medicine
From the journal Journal of Perinatal Medicine Volume 50 Issue 3

Abstract

Objectives

Although neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) receive therapeutic hypothermia (TH), 40–50% die or have significant neurological disability. The aim of this study is to analyse the association of placental pathology and neurodevelopmental outcome in cooled neonates with HIE at 18–24 months of age.

Methods

Retrospective analysis of prospectively collected data on 120 neonates registered in the Swiss National Asphyxia and Cooling Register born between 2007 and 2017. This descriptive study examines the frequency and range of pathologic findings in placentas of neonates with HIE. Placenta pathology was available of 69/120 neonates, whose results are summarized as placental findings. As neonates with HIE staged Sarnat score 1 (21/69) did not routinely undergo follow-up assessments and of six neonates staged Sarnat Score 2/3 no follow-up assessments were available, 42/48 (88%) neonates remain to assess the association between placental findings and outcome.

Results

Of the 42/48 (88%) neonates with available follow up 29% (12/42) neonates died. Major placenta abnormalities occurred in 48% (20/42). Major placenta abnormality was neither associated with outcome at 18–24 months of age (OR 1.75 [95% CI 0.50–6.36, p=0.381]), nor with death by 2 years of age (OR 1.96 [95% CI 0.53–7.78, p=0.320]).

Conclusions

In this study cohort there could not be shown an association between the placenta findings and the neurodevelopmental outcome at 18–24 months of age.

Keywords: hypoxic ischemic encephalopathy; neonates; neurodevelopmental outcome; placenta pathology; therapeutic hypothermia
Corresponding author: Barbara Brotschi, MD, Department of Paediatric and Neonatal Intensive Care, University Children’s Hospital Zurich, Steinwiesstr. 75, 8032 Zurich, Switzerland, Phone: +41 44 266 7064, Fax: +41 44 266 7168, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

References

1. McIntyre, S, Badawi, N, Blair, E, Nelson, KB. Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment? Dev Med Child Neurol 2015;57(3 Suppl):2–7. https://doi.org/10.1111/dmcn.12725.Search in Google Scholar PubMed

2. Mir, IN, Johnson-Welch, SF, Nelson, DB, Brown, LS, Rosenfeld, CR, Chalak, LF. Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia. Am J Obstet Gynecol 2015;213:849.e1–7. https://doi.org/10.1016/j.ajog.2015.09.072.Search in Google Scholar PubMed

3. Executive summary: neonatal encephalopathy and neurologic outcome, second edition. Report of the American college of obstetricians and gynecologists’ task force on neonatal encephalopathy. Obstet Gynecol 2014;123:896–901. https://doi.org/10.1097/01.AOG.0000445580.65983.d2.Search in Google Scholar PubMed

4. Chalak, LF. Inflammatory biomarkers of birth asphyxia. Clin Perinatol 2016;43:501–10. https://doi.org/10.1016/j.clp.2016.04.008.Search in Google Scholar PubMed PubMed Central

5. Massaro, AN, Evangelou, I, Brown, J, Fatemi, A, Vezina, G, McCarter, R, et al.. Neonatal neurobehavior after therapeutic hypothermia for hypoxic ischemic encephalopathy. Early Hum Dev 2015;91:593–9. https://doi.org/10.1016/j.earlhumdev.2015.07.008.Search in Google Scholar PubMed PubMed Central

6. Papile, LA, Baley, JE, Benitz, W, Cummings, J, Carlo, WA, Eichenwald, E, et al.. Hypothermia and neonatal encephalopathy. Pediatrics 2014;133:1146–50. https://doi.org/10.1542/peds.2014-0899.Search in Google Scholar PubMed

7. Shankaran, S, Laptook, AR, McDonald, SA, Hintz, SR, Barnes, PD, Das, A, et al.. Acute perinatal sentinel events, neonatal brain injury pattern, and outcome of infants undergoing a trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr 2017;180:275–8.e2. https://doi.org/10.1016/j.jpeds.2016.09.026.Search in Google Scholar PubMed PubMed Central

8. Wintermark, P, Boyd, T, Gregas, MC, Labrecque, M, Hansen, A. Placental pathology in asphyxiated newborns meeting the criteria for therapeutic hypothermia. Am J Obstet Gynecol 2010;203:579.e1–9. https://doi.org/10.1016/j.ajog.2010.08.024.Search in Google Scholar PubMed

9. Hayes, BC, Cooley, S, Donnelly, J, Doherty, E, Grehan, A, Madigan, C, et al.. The placenta in infants >36 weeks gestation with neonatal encephalopathy: a case control study. Arch Dis Child Fetal Neonatal Ed 2013;98:F233–9. https://doi.org/10.1136/archdischild-2012-301992.Search in Google Scholar PubMed

10. Badawi, N, Kurinczuk, JJ, Keogh, JM, Alessandri, LM, O’Sullivan, F, Burton, PR, et al.. Intrapartum risk factors for newborn encephalopathy: the western Australian case-control study. BMJ 1998;317:1554–8. https://doi.org/10.1136/bmj.317.7172.1554.Search in Google Scholar PubMed PubMed Central

11. Badawi, N, Kurinczuk, JJ, Keogh, JM, Alessandri, LM, O’Sullivan, F, Burton, PR, et al.. Antepartum risk factors for newborn encephalopathy: the western Australian case-control study. BMJ 1998;317:1549–53. https://doi.org/10.1136/bmj.317.7172.1549.Search in Google Scholar PubMed PubMed Central

12. Ellis, M, de L Costello, AM. Antepartum risk factors for newborn encephalopathy. Intrapartum risk factors are important in developing world. BMJ 1999;318:1414–5. https://doi.org/10.1136/bmj.318.7195.1414.Search in Google Scholar

13. Martinez-Biarge, M, Diez-Sebastian, J, Wusthoff, CJ, Mercuri, E, Cowan, FM. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics 2013;132:e952–9. https://doi.org/10.1542/peds.2013-0511.Search in Google Scholar PubMed

14. Parker, SJ, Kuzniewicz, M, Niki, H, Wu, YW. Antenatal and intrapartum risk factors for hypoxic-ischemic encephalopathy in a US birth cohort. J Pediatr 2018;203:163–9. https://doi.org/10.1016/j.jpeds.2018.08.028.Search in Google Scholar PubMed

15. Tann, CJ, Nakakeeto, M, Willey, BA, Sewegaba, M, Webb, EL, Oke, I, et al.. Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study. Arch Dis Child Fetal Neonatal Ed 2018;103:F250–F6. https://doi.org/10.1136/archdischild-2017-312744.Search in Google Scholar PubMed PubMed Central

16. Scheidegger, S, Held, U, Grass, B, Latal, B, Hagmann, C, Brotschi, B, et al.. Association of perinatal risk factors with neurological outcome in neonates with hypoxic ischemic encephalopathy. J Matern Fetal Neonatal Med 2019:1–8. https://doi.org/10.1080/14767058.2019.1623196.Search in Google Scholar PubMed

17. Fleiss, B, Tann, CJ, Degos, V, Sigaut, S, Van Steenwinckel, J, Schang, AL, et al.. Inflammation-induced sensitization of the brain in term infants. Dev Med Child Neurol 2015;57(3 Suppl):17–28. https://doi.org/10.1111/dmcn.12723.Search in Google Scholar PubMed

18. Vik, T, Redline, R, Nelson, KB, Bjellmo, S, Vogt, C, Ng, P, et al.. The placenta in neonatal encephalopathy: a case-control study. J Pediatr 2018;202:77–85.e3. https://doi.org/10.1016/j.jpeds.2018.06.005.Search in Google Scholar PubMed

19. Bingham, A, Gundogan, F, Rand, K, Laptook, AR. Placental findings among newborns with hypoxic ischemic encephalopathy. J Perinatol 2019;39:563–70. https://doi.org/10.1038/s41372-019-0334-9.Search in Google Scholar PubMed

20. Hagmann, CF, Brotschi, B, Bernet, V, Latal, B, Berger, TM, Robertson, NJ. Hypothermia for perinatal asphyxial encephalopathy. Swiss Med Wkly 2011;141:w13145. https://doi.org/10.4414/smw.2011.13145.Search in Google Scholar PubMed

21. Brotschi, B, Grass, B, Ramos, G, Beck, I, Held, U, Hagmann, C, et al.. The impact of a register on the management of neonatal cooling in Switzerland. Early Hum Dev 2015;91:277–84. https://doi.org/10.1016/j.earlhumdev.2015.02.009.Search in Google Scholar PubMed

22. Khong, TY, Mooney, EE, Ariel, I, Balmus, NC, Boyd, TK, Brundler, MA, et al.. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med 2016;140:698–713. https://doi.org/10.5858/arpa.2015-0225-cc.Search in Google Scholar PubMed

23. Pinar, H, Sung, CJ, Oyer, CE, Singer, DB. Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med 1996;16:901–7. https://doi.org/10.3109/15513819609168713.Search in Google Scholar

24. Sarnat, HB, Sarnat, MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976;33:696–705. https://doi.org/10.1001/archneur.1976.00500100030012.Search in Google Scholar PubMed

25. Bayley, N. Bayley scales of infant development, 2nd ed. San Antonio, TX: The Psychological Corp; 1993.Search in Google Scholar

26. Bayley, N. Bayley scales of infant and toddler development, 3rd ed. San Antonio, TX: Harcourt Assessment Inc; 2006.10.1037/t14978-000Search in Google Scholar

27. Palisano, R, Rosenbaum, P, Walter, S, Russell, D, Wood, E, Galuppi, B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 1997;39:214–23. https://doi.org/10.1111/j.1469-8749.1997.tb07414.x.Search in Google Scholar PubMed

28. Jary, S, Whitelaw, A, Walløe, L, Thoresen, M. Comparison of Bayley-2 and Bayley-3 scores at 18 months in term infants following neonatal encephalopathy and therapeutic hypothermia. Dev Med Child Neurol 2013;55:1053–9. https://doi.org/10.1111/dmcn.12208.Search in Google Scholar PubMed PubMed Central

29. Laptook, AR, Shankaran, S, Tyson, JE, Munoz, B, Bell, EF, Goldberg, RN, et al.. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial. J Am Med Assoc 2017;318:1550–60. https://doi.org/10.1001/jama.2017.14972.Search in Google Scholar PubMed PubMed Central

30. Shankaran, S, Laptook, AR, Ehrenkranz, RA, Tyson, JE, McDonald, SA, Donovan, EF, et al.. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574–84. https://doi.org/10.1056/nejmcps050929.Search in Google Scholar

31. Azzopardi, DV, Strohm, B, Edwards, AD, Dyet, L, Halliday, HL, Juszczak, E, et al.. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009;361:1349–58. https://doi.org/10.1056/nejmoa0900854.Search in Google Scholar PubMed

32. von Elm, E, Altman, DG, Egger, M, Pocock, SJ, Gøtzsche, PC, Vandenbroucke, JP, et al.. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370:1453–7. https://doi.org/10.1016/s0140-6736(07)61602-x.Search in Google Scholar

33. Harteman, JC, Nikkels, PG, Benders, MJ, Kwee, A, Groenendaal, F, de Vries, LS. Placental pathology in full-term infants with hypoxic-ischemic neonatal encephalopathy and association with magnetic resonance imaging pattern of brain injury. J Pediatr 2013;163:968–95.e2. https://doi.org/10.1016/j.jpeds.2013.06.010.Search in Google Scholar PubMed

34. Biselele, T, Naulaers, G, Bunga Muntu, P, Nkidiaka, E, Kapepela, M, Mavinga, L, et al.. A descriptive study of perinatal asphyxia at the University Hospital of Kinshasa (Democratic Republic of Congo). J Trop Pediatr 2013;59:274–9. https://doi.org/10.1093/tropej/fmt011.Search in Google Scholar PubMed

35. Nasiell, J, Papadogiannakis, N, Löf, E, Elofsson, F, Hallberg, B. Hypoxic ischemic encephalopathy in newborns linked to placental and umbilical cord abnormalities. J Matern Fetal Neonatal Med 2016;29:721–6. https://doi.org/10.3109/14767058.2015.1015984.Search in Google Scholar PubMed

36. Volpe, JJ. Placental assessment provides insight into mechanisms and timing of neonatal hypoxic-ischemic encephalopathy. J Neonatal Perinat Med 2019;12:113–6. https://doi.org/10.3233/npm-190270.Search in Google Scholar

37. Wu, YW, Goodman, AM, Chang, T, Mulkey, SB, Gonzalez, FF, Mayock, DE, et al.. Placental pathology and neonatal brain MRI in a randomized trial of erythropoietin for hypoxic-ischemic encephalopathy. Pediatr Res 2020;87:879–84. https://doi.org/10.1038/s41390-019-0493-6.Search in Google Scholar PubMed

38. Jantzie, LL, Robinson, S. Placenta and perinatal brain injury: the gateway to individualized therapeutics and precision neonatal medicine. Pediatr Res 2020;87:807–8. https://doi.org/10.1038/s41390-020-0807-8.Search in Google Scholar PubMed

Received: 2020-12-09
Accepted: 2021-10-07
Published Online: 2021-10-21
Published in Print: 2022-03-28

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Corner of Academy
  3. Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies
  4. Adverse perinatal outcomes following the prenatal diagnosis of isolated single umbilical artery in singleton pregnancies: a systematic review and meta-analysis
  5. Original Articles – Obstetrics
  6. Perinatal outcomes in women with severe acute respiratory syndrome coronavirus 2 infection: comparison with contemporary and matched pre-COVID-19 controls
  7. The postpartum period during the COVID-19 pandemic: investigating Turkish women’s postpartum support and postpartum-specific anxiety
  8. First-line noninvasive management of cytomegalovirus primary infection in pregnancy
  9. Ultrasound and magnetic resonance imaging in the diagnosis of clinically significant placenta accreta spectrum disorders
  10. Improved management of placenta accreta spectrum disorders: experience from a single institution
  11. A randomized controlled trial of two-doses of vaginal progesterone 400 vs. 200 mg for prevention of preterm labor in twin gestations
  12. The impact of preimplantation genetic testing for aneuploidy on prenatal screening
  13. Original Articles – Fetus
  14. Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study
  15. HDlive Flow Silhouette with spatiotemporal image correlation for assessment of fetal cardiac structures at 12 to 14 + 6 weeks of gestation
  16. Umbilical artery pulsatility index and half-peak systolic velocity in second- and third-trimester fetuses with trisomy 18 and 13
  17. Original Articles – Neonates
  18. Pulmonary hypertension in infants with bronchopulmonary dysplasia: risk factors, mortality and duration of hospitalisation
  19. Outcomes from birth to 6 months of publicly insured infants born to mothers with severe acute respiratory syndrome coronavirus 2 infection in the United States
  20. Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy – an 11-year single-center experience
  21. High frequency band limits in spectral analysis of heart rate variability in preterm infants
  22. Bacterial DNA detection in very preterm infants assessed for risk of early onset sepsis
  23. Short Communication
  24. Healthcare workers’ attitudes about vaccination of pregnant women and those wishing to become pregnant
  25. Letter to the Editors
  26. Comment on Abdel Wahab et al.: A randomized controlled trial of two-doses of vaginal progesterone 400 vs. 200 mg for prevention of preterm labor in twin gestations
  27. Re: Comment on Abdel Wahab et al.: A randomized controlled trial of two-doses of vaginal progesterone 400 vs. 200 mg for prevention of preterm labor in twin gestations
  28. SARS-CoV-2 behavior, through the eyes of a perinatologist?
  29. Re: SARS-CoV-2 behavior, through the eyes of a perinatologist?
https://doi.org/10.1515/jpm-2020-0583
Keywords for this article
hypoxic ischemic encephalopathy; neonates; neurodevelopmental outcome; placenta pathology; therapeutic hypothermia

Articles in the same Issue

  1. Frontmatter
  2. Corner of Academy
  3. Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies
  4. Adverse perinatal outcomes following the prenatal diagnosis of isolated single umbilical artery in singleton pregnancies: a systematic review and meta-analysis
  5. Original Articles – Obstetrics
  6. Perinatal outcomes in women with severe acute respiratory syndrome coronavirus 2 infection: comparison with contemporary and matched pre-COVID-19 controls
  7. The postpartum period during the COVID-19 pandemic: investigating Turkish women’s postpartum support and postpartum-specific anxiety
  8. First-line noninvasive management of cytomegalovirus primary infection in pregnancy
  9. Ultrasound and magnetic resonance imaging in the diagnosis of clinically significant placenta accreta spectrum disorders
  10. Improved management of placenta accreta spectrum disorders: experience from a single institution
  11. A randomized controlled trial of two-doses of vaginal progesterone 400 vs. 200 mg for prevention of preterm labor in twin gestations
  12. The impact of preimplantation genetic testing for aneuploidy on prenatal screening
  13. Original Articles – Fetus
  14. Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study
  15. HDlive Flow Silhouette with spatiotemporal image correlation for assessment of fetal cardiac structures at 12 to 14 + 6 weeks of gestation
  16. Umbilical artery pulsatility index and half-peak systolic velocity in second- and third-trimester fetuses with trisomy 18 and 13
  17. Original Articles – Neonates
  18. Pulmonary hypertension in infants with bronchopulmonary dysplasia: risk factors, mortality and duration of hospitalisation
  19. Outcomes from birth to 6 months of publicly insured infants born to mothers with severe acute respiratory syndrome coronavirus 2 infection in the United States
  20. Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy – an 11-year single-center experience
  21. High frequency band limits in spectral analysis of heart rate variability in preterm infants
  22. Bacterial DNA detection in very preterm infants assessed for risk of early onset sepsis
  23. Short Communication
  24. Healthcare workers’ attitudes about vaccination of pregnant women and those wishing to become pregnant
  25. Letter to the Editors
  26. Comment on Abdel Wahab et al.: A randomized controlled trial of two-doses of vaginal progesterone 400 vs. 200 mg for prevention of preterm labor in twin gestations
  27. Re: Comment on Abdel Wahab et al.: A randomized controlled trial of two-doses of vaginal progesterone 400 vs. 200 mg for prevention of preterm labor in twin gestations
  28. SARS-CoV-2 behavior, through the eyes of a perinatologist?
  29. Re: SARS-CoV-2 behavior, through the eyes of a perinatologist?
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 26.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/jpm-2020-0583/html
Scroll to top button