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Review

The Placenta and Neonatal Encephalopathy with a Focus on Hypoxic-Ischemic Encephalopathy

Pages 950-971 | Received 30 Jun 2023, Accepted 15 Sep 2023, Published online: 27 Sep 2023

References

  • Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015;169(4):397–403. doi:10.1001/jamapediatrics.2014.3269.
  • Russ JB, Simmons R, Glass HC. Neonatal encephalopathy: beyond hypoxic-ischemic encephalopathy. Neoreviews. 2021;22(3):e148–e162. doi:10.1542/neo.22-3-e148.
  • Sandoval Karamian AG, Mercimek-Andrews S, Mohammad K, Molloy EJ, Chang T, Chau V, Murray DM, Wusthoff CJ, Newborn Brain Society Guidelines and Publications Committee. Neonatal encephalopathy: etiologies other than hypoxic-ischemic encephalopathy. Semin Fetal Neonatal Med. 2021;26(5):101272. doi:10.1016/j.siny.2021.101272.
  • 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(4):896–901.
  • Inder TE, Volpe JJ, Anderson PJ. Defining the neurologic consequences of preterm birth. N Engl J Med. 2023;389(5):441–53. doi:10.1056/NEJMra2303347.
  • Chen X, Malaeb SN, Pan J, Wang L, Scafidi J. Editorial: perinatal hypoxic-ischemic brain injury: mechanisms, pathogenesis, and potential therapeutic strategies. Front Cell Neurosci. 2022;16:1086692. doi:10.3389/fncel.2022.1086692.
  • Mehta N, Shah P, Bhide A. Neonatal encephalopathy-controversies and evidence. Acta Obstet Gynecol Scand. 2022;101(9):938–40. doi:10.1111/aogs.14416.
  • Gunn AJ, Thoresen M. Neonatal encephalopathy and hypoxic-ischemic encephalopathy. Handb Clin Neurol. 2019;162:217–37.
  • Greco P, Nencini G, Piva I, Scioscia M, Volta CA, Spadaro S, Neri M, Bonaccorsi G, Greco F, Cocco I, et al. Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future. Acta Neurol Belg. 2020;120(2):277–88. doi:10.1007/s13760-020-01308-3.
  • Bonifacio SL, Hutson S. The term newborn: evaluation for hypoxic-ischemic encephalopathy. Clin Perinatol. 2021;48(3):681–95. doi:10.1016/j.clp.2021.05.014.
  • Glass HC. Hypoxic-ischemic encephalopathy and other neonatal encephalopathies. Continuum. 2018;24(1):57–71. doi:10.1212/CON.0000000000000557.
  • Ayres-de-Campos D. Introduction: why is intrapartum foetal monitoring necessary – impact on outcomes and interventions. Best Pract Res Clin Obstet Gynaecol. 2016;30:3–8. doi:10.1016/j.bpobgyn.2015.06.004.
  • Esplin MS. The goal of continuous fetal heart rate monitoring during labor: have we been successful? Clin Obstet Gynecol. 2020;63(3):601–6. doi:10.1097/GRF.0000000000000543.
  • Torbenson VE, Tolcher MC, Nesbitt KM, Colby CE, El-Nashar SA, Gostout BS, Weaver AL, Mc Gree ME, Famuyide AO. Intrapartum factors associated with neonatal hypoxic ischemic encephalopathy: a case-controlled study. BMC Pregnancy Childbirth. 2017;17(1):415. doi:10.1186/s12884-017-1610-3.
  • Acun C, Karnati S, Padiyar S, Puthuraya S, Aly H, Mohamed M. Trends of neonatal hypoxic-ischemic encephalopathy prevalence and associated risk factors in the United States, 2010 to 2018. Am J Obstet Gynecol. 2022;227(5):751.e1–10. doi:10.1016/j.ajog.2022.06.002.
  • Gaccioli F, Lager S. Placental nutrient transport and intrauterine growth restriction. Front Physiol. 2016;7:40. doi:10.3389/fphys.2016.00040.
  • Monaco-Brown M, Munshi U, Horgan MJ, Gifford JL, Khalak R. Association of maternal obesity and neonatal hypoxic-ischemic encephalopathy. Front Pediatr. 2022;10:850654. doi:10.3389/fped.2022.850654.
  • Huang T, Huang X, Li H, Qi J, Wang N, Xu Y, Zeng Y, Xiao X, Liu R, Chan YL, et al. Maternal cigarette smoke exposure exaggerates the behavioral defects and neuronal loss caused by hypoxic-ischemic brain injury in female offspring. Front Cell Neurosci. 2022;16:818536. doi:10.3389/fncel.2022.818536.
  • 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. doi:10.1016/j.jpeds.2018.08.028.
  • Rossi AC, Prefumo F. Antepartum and intrapartum risk factors for neonatal hypoxic-ischemic encephalopathy: a systematic review with meta-analysis. Curr Opin Obstet Gynecol. 2019;31(6):410–7. doi:10.1097/GCO.0000000000000581.
  • Peebles PJ, Duello TM, Eickhoff JC, McAdams RM. Antenatal and intrapartum risk factors for neonatal hypoxic ischemic encephalopathy. J Perinatol. 2020;40(1):63–9. doi:10.1038/s41372-019-0531-6.
  • Locatelli A, Lambicchi L, Incerti M, Bonati F, Ferdico M, Malguzzi S, Torcasio F, Calzi P, Varisco T, Paterlini G, et al. Is perinatal asphyxia predictable? BMC Pregnancy Childbirth. 2020;20(1):186. doi:10.1186/s12884-020-02876-1.
  • Novak CM, Eke AC, Ozen M, Burd I, Graham EM. Risk factors for neonatal hypoxic-ischemic encephalopathy in the absence of sentinel events. Am J Perinatol. 2019;36(1):27–33.
  • Turco MY, Moffett A. Development of the human placenta. Development. 2019;146(22):1–14. doi:10.1242/dev.163428.
  • Uenaka M, Morizane M, Tanimura K, Deguchi M, Kanzawa M, Itoh T, Yamada H. Histopathological analysis of placentas with congenital cytomegalovirus infection. Placenta. 2019;75:62–7. doi:10.1016/j.placenta.2019.01.003.
  • Chapel DB, Choy B, Pytel P, Husain AN, Lastra RR. Mucolipidosis type II affecting 1 fetus and placental disk of a dichorionic-diamnionic twin gestation: a case report and review of the literature. Int J Gynecol Pathol. 2019;38(4):346–52. doi:10.1097/PGP.0000000000000506.
  • Langston C, Kaplan C, Macpherson T, 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(5):449–76.
  • Odibo I, Gehlot A, Ounpraseuth ST, Magann EF. Pathologic examination of the placenta and its clinical utility: a survey of obstetrics and gynecology providers. J Matern Fetal Neonatal Med. 2016;29(2):197–201. doi:10.3109/14767058.2014.998192.
  • Spencer MK, Khong TY. Conformity to guidelines for pathologic examination of the placenta. Arch Pathol Lab Med. 2003;127(2):205–7. doi:10.5858/2003-127-205-CTGFPE.
  • Karaye KM, Sa’idu H, Balarabe SA, Ishaq NA, Adamu UG, Mohammed IY, Oboirien I, Umuerri EM, Mankwe AC, Shidali VY, et al. Clinical features and outcomes of peripartum cardiomyopathy in Nigeria. J Am Coll Cardiol. 2020;76(20):2352–64. doi:10.1016/j.jacc.2020.09.540.
  • Roberts DJ, Baergen RN, Boyd TK, Carreon CK, Duncan VE, Ernst LM, Faye-Petersen OM, Folkins AK, Hecht JL, Heerema-McKenney A, et al. Criteria for placental examination for obstetrical and neonatal providers. Am J Obstet Gynecol. 2023;228(5):497–508.e494. doi:10.1016/j.ajog.2022.12.017.
  • Dunlop AL, Essalmi AG, Alvalos L, Breton C, Camargo CA, Cowell WJ, Dabelea D, Dager SR, Duarte C, Elliott A, et al. Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: findings from the ECHO cohorts. PLOS One. 2021;16(1):e0245064. doi:10.1371/journal.pone.0245064.
  • Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler M-A, Derricott H, Evans MJ, Faye-Petersen OM, Gillan JE, et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016;140(7):698–713. doi:10.5858/arpa.2015-0225-CC.
  • Redline RW, Ravishankar S, Bagby CM, Saab ST, Zarei S. Four major patterns of placental injury: a stepwise guide for understanding and implementing the 2016 Amsterdam consensus. Mod Pathol. 2021;34(6):1074–92. doi:10.1038/s41379-021-00747-4.
  • Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol. 2015;213(4 Suppl):S29–S52. doi:10.1016/j.ajog.2015.08.040.
  • Gomez-Lopez N, Galaz J, Miller D, Farias-Jofre M, Liu Z, Arenas-Hernandez M, Garcia-Flores V, Shaffer Z, Greenberg JM, Theis KR, et al. The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal-fetal homeostasis. Reproduction. 2022;164(2):R11–45. doi:10.1530/REP-22-0046.
  • Jung E, Romero R, Yeo L, Diaz-Primera R, Marin-Concha J, Para R, Lopez AM, Pacora P, Gomez-Lopez N, Yoon BH, et al. The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications. Semin Fetal Neonatal Med. 2020;25(4):101146. doi:10.1016/j.siny.2020.101146.
  • Chiesa C, Pacifico L, Natale F, Hofer N, Osborn JF, Resch B. Fetal and early neonatal interleukin-6 response. Cytokine. 2015;76(1):1–12. doi:10.1016/j.cyto.2015.03.015.
  • Salafia CM, Misra DP. Histopathology of the fetal inflammatory response to intra-amniotic pathogens. Semin Fetal Neonatal Med. 2020;25(4):101128. doi:10.1016/j.siny.2020.101128.
  • Redline RW, Ravishankar S. Fetal vascular malperfusion, an update. APMIS. 2018;126(7):561–9. doi:10.1111/apm.12849.
  • Kaplan CG. Fetal and maternal vascular lesions. Semin Diagn Pathol. 2007;24(1):14–22. doi:10.1053/j.semdp.2007.02.005.
  • Heider A. Fetal vascular malperfusion. Arch Pathol Lab Med. 2017;141(11):1484–9. doi:10.5858/arpa.2017-0212-RA.
  • Stanek J. Distal villous lesions are clinically more relevant than proximal large muscular vessel lesions of placental fetal vascular malperfusion. Histol Histopathol. 2022;37(4):365–72.
  • Stanek J. Placental infectious villitis versus villitis of unknown etiology. Pol J Pathol. 2017;68(1):55–65. doi:10.5114/pjp.2017.67616.
  • Goldstein JA, Gallagher K, Beck C, Kumar R, Gernand AD. Maternal-fetal inflammation in the placenta and the developmental origins of health and disease. Front Immunol. 2020;11:531543. doi:10.3389/fimmu.2020.531543.
  • Redline RW. Villitis of unknown etiology: noninfectious chronic villitis in the placenta. Hum Pathol. 2007;38(10):1439–46. doi:10.1016/j.humpath.2007.05.025.
  • Kim CJ, Romero R, Chaemsaithong P, Kim JS. Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance. Am J Obstet Gynecol. 2015;213(4 Suppl):S53–S69. doi:10.1016/j.ajog.2015.08.041.
  • Cornish EF, McDonnell T, Williams DJ. Chronic inflammatory placental disorders associated with recurrent adverse pregnancy outcome. Front Immunol. 2022;13:825075. doi:10.3389/fimmu.2022.825075.
  • de Koning L, Crawford S, Nohr E, Chadha R, Horn C, Wright JR, Chan ES. Recurrence risk of villitis of unknown etiology: analysis of a large retrospective cohort study, systematic review and meta-analysis. Placenta. 2022;120:32–9. doi:10.1016/j.placenta.2022.02.006.
  • Eastman NJ, Deleon M. The etiology of cerebral palsy. Am J Obstet Gynecol. 1955;69(5):950–61. doi:10.1016/0002-9378(55)90094-6.
  • Goncalves LF, Cornejo P, Towbin R. Neuroimaging findings associated with the fetal inflammatory response syndrome. Semin Fetal Neonatal Med. 2020;25(4):101143. doi:10.1016/j.siny.2020.101143.
  • Yap V, Perlman JM. Mechanisms of brain injury in newborn infants associated with the fetal inflammatory response syndrome. Semin Fetal Neonatal Med. 2020;25(4):101110. doi:10.1016/j.siny.2020.101110.
  • Pathak S, Lees CC, Hackett G, Jessop F, Sebire NJ. Frequency and clinical significance of placental histological lesions in an unselected population at or near term. Virchows Arch. 2011;459(6):565–72. doi:10.1007/s00428-011-1157-z.
  • Bar J, Schreiber L, Golan A, Kovo M. Placental factor in spontaneous term labor in uncomplicated pregnancy. J Matern Fetal Neonatal Med. 2012;25(12):2704–7. doi:10.3109/14767058.2012.704450.
  • Lee J, Kim J-S, Park JW, Park C-W, Park JS, Jun JK, Yoon BH. Chronic chorioamnionitis is the most common placental lesion in late preterm birth. Placenta. 2013;34(8):681–9. doi:10.1016/j.placenta.2013.04.014.
  • Romero R, Kim YM, Pacora P, Kim CJ, Benshalom-Tirosh N, Jaiman S, Bhatti G, Kim J-S, Qureshi F, Jacques SM, et al. The frequency and type of placental histologic lesions in term pregnancies with normal outcome. J Perinat Med. 2018;46(6):613–30. doi:10.1515/jpm-2018-0055.
  • Stanek J. Comparison of placental pathology in preterm, late-preterm, near-term, and term births. Am J Obstet Gynecol. 2014;210(3):234.e231–6. doi:10.1016/j.ajog.2013.10.015.
  • American Academy Of Pediatrics Committee On F, Newborn, American College Of O, Gynecologists Committee On Obstetric P. The Apgar Score. Pediatrics. 2015;136(4):819–22.
  • Gruenwald P. Fetal deprivation and placental pathology: concepts and relationships. Perspect Pediatr Pathol. 1975;2:101–49.
  • McDonald DGM, Kelehan P, McMenamin JB, Gorman WA, Madden D, Tobbia IN, Mooney EE. Placental fetal thrombotic vasculopathy is associated with neonatal encephalopathy. Hum Pathol. 2004;35(7):875–80. doi:10.1016/j.humpath.2004.02.014.
  • 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(6):579.e571–9. doi:10.1016/j.ajog.2010.08.024.
  • Hayes BC, Cooley S, Donnelly J, Doherty E, Grehan A, Madigan C, McGarvey C, Mulvany S, Ryan S, Gillian J, et al. The placenta in infants >36 weeks gestation with neonatal encephalopathy: a case control study. Arch Dis Child Fetal Neonatal Ed. 2013;98(3):F233–9. doi:10.1136/archdischild-2012-301992.
  • 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(6):849.e841–7.
  • Vik T, Redline R, Nelson KB, Bjellmo S, Vogt C, Ng P, Strand KM, Nu TNT, Oskoui M. The Placenta in neonatal encephalopathy: a case-control study. J Pediatr. 2018;202:77–85.e73. doi:10.1016/j.jpeds.2018.06.005.
  • Benz LD, Bode PK, Brandt S, Grass B, Hagmann C, Liamlahi R, Frey B, Held U, Brotschi B. Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy – an 11-year single-center experience. J Perinat Med. 2022;50(3):343–50. doi:10.1515/jpm-2020-0583.
  • Chalak L, Redline RW, Goodman AM, Juul SE, Chang T, Yanowitz TD, Maitre N, Mayock DE, Lampland AL, Bendel-Stenzel E, et al. Acute and chronic placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy. J Pediatr. 2021;237:190–6. doi:10.1016/j.jpeds.2021.06.023.
  • Bingham A, Gundogan F, Rand K, Laptook AR. Placental findings among newborns with hypoxic ischemic encephalopathy. J Perinatol. 2019;39(4):563–70. doi:10.1038/s41372-019-0334-9.
  • Espinoza ML, Brundler M-A, Hasan SU, Mohammad K, Momin S, Al Shaikh B, Yusuf K. Placental pathology as a marker of brain injury in infants with hypoxic ischemic encephalopathy. Early Hum Dev. 2022;174:105683. doi:10.1016/j.earlhumdev.2022.105683.
  • Redline RW, O'Riordan MA. Placental lesions associated with cerebral palsy and neurologic impairment following term birth. Arch Pathol Lab Med. 2000;124(12):1785–91. doi:10.5858/2000-124-1785-PLAWCP.
  • Redline RW. Severe fetal placental vascular lesions in term infants with neurologic impairment. Am J Obstet Gynecol. 2005;192(2):452–7. doi:10.1016/j.ajog.2004.07.030.
  • Phelan JP, Korst LM, Martin GI. Application of criteria developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy to acutely asphyxiated neonates. Obstet Gynecol. 2011;118(4):824–30. doi:10.1097/AOG.0b013e31822f1713.
  • Ravishankar S, Redline RW. The placenta. Handb Clin Neurol. 2019;162:57–66.
  • 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(4):968–95.e962. doi:10.1016/j.jpeds.2013.06.010.
  • Evensen TL, Vik T, Andersen GL, Bjellmo S, Hollung SJ. Prevalence, birth, and clinical characteristics of dyskinetic cerebral palsy compared with spastic cerebral palsy subtypes: a Norwegian register-based study. Dev Med Child Neurol. 2023;00:1–11. doi:10.1111/dmcn.15598.
  • Kim C, Carreon K, James K, Boyd T, Drucilla R. Umbilical cord abnormalities and placental inflammation associated with neonatal hypoxic-ischemic encephalopathy. Pediatr Dev Pathol. 2023;26(2):176–236.
  • Stanek J, Biesiada J, Trzeszcz M. Clinicoplacental phenotypes vary with gestational age: an analysis by classical and clustering methods. Acta Obstet Gynecol Scand. 2014;93(4):392–8. doi:10.1111/aogs.12350.
  • Freedman AA, Keenan-Devlin LS, Borders A, Miller GE, Ernst LM. Formulating a maningful and comprehensive placental phenotypic classification. Pediatr Dev Pathol. 2021;24(4):337–50. doi:10.1177/10935266211008444.
  • Penn AA, Wintermark P, Chalak LF, Armstrong J, Redline R, Scher MS, Nelson KB, Newborn Brain Society Guidelines and Publications Committee. Placental contribution to neonatal encephalopathy. Semin Fetal Neonatal Med. 2021;26(4):101276. doi:10.1016/j.siny.2021.101276.
  • Ebbing C, Kiserud T, Johnsen SL, Albrechtsen S, Rasmussen S. Prevalence, risk factors and outcomes of velamentous and marginal cord insertions: a population-based study of 634,741 pregnancies. PLOS One. 2013;8(7):e70380. doi:10.1371/journal.pone.0070380.
  • Visentin S, Londero AP, Santoro L, Pizzi S, Andolfatto M, Venturini M, Saraggi D, Coati I, Sacchi D, Rugge M, et al. Abnormal umbilical cord insertions in singleton deliveries: placental histology and neonatal outcomes. J Clin Pathol. 2022;75(11):751–8. doi:10.1136/jclinpath-2020-207342.
  • Nkwabong E, Njikam F, Kalla G. Outcome of pregnancies with marginal umbilical cord insertion. J Matern Fetal Neonatal Med. 2021;34(7):1133–7. doi:10.1080/14767058.2019.1628206.
  • Luo G, Redline RW. Peripheral insertion of umbilical cord. Pediatr Dev Pathol. 2013;16(6):399–404. doi:10.2350/13-05-1337-OA.1.
  • Tantbirojn P, Saleemuddin A, Sirois K, Crum CP, Boyd TK, Tworoger S, Parast MM. Gross abnormalities of the umbilical cord: related placental histology and clinical significance. Placenta. 2009;30(12):1083–8. doi:10.1016/j.placenta.2009.09.005.
  • Jessop FA, Lees CC, Pathak S, Hook CE, Sebire NJ. Umbilical cord coiling: clinical outcomes in an unselected population and systematic review. Virchows Arch. 2014;464(1):105–12. doi:10.1007/s00428-013-1513-2.
  • Olaya CM, Gil F, Salcedo JD, Salazar AJ, Silva JL, Bernal JE. Anatomical pathology of the umbilical cord and its maternal and fetal clinical associations in 434 newborns. Pediatr Dev Pathol. 2018;21(5):467–74. doi:10.1177/1093526618758204.
  • Pinar H, Carpenter M. Placenta and umbilical cord abnormalities seen with stillbirth. Clin Obstet Gynecol. 2010;53(3):656–72. doi:10.1097/GRF.0b013e3181eb68fe.
  • Stanek J. Association of coexisting morphological umbilical cord abnormality and clinical cord compromise with hypoxic and thrombotic placental histology. Virchows Arch. 2016;468(6):723–32. doi:10.1007/s00428-016-1921-1.
  • Slack JC, Boyd TK. Fetal vascular malperfusion due to long and hypercoiled umbilical cords resulting in recurrent second trimester pregnancy loss: a case series and literature review. Pediatr Dev Pathol. 2021;24(1):12–8. doi:10.1177/1093526620962061.
  • Ernst LM, Minturn L, Huang MH, Curry E, Su EJ. Gross patterns of umbilical cord coiling: correlations with placental histology and stillbirth. Placenta. 2013;34(7):583–8. doi:10.1016/j.placenta.2013.04.002.
  • Becroft DM, Thompson JM, Mitchell EA. The epidemiology of placental infarction at term. Placenta. 2002;23(4):343–51. doi:10.1053/plac.2001.0777.
  • Becroft DM, Thompson JM, Mitchell EA. Placental infarcts, intervillous fibrin plaques, and intervillous thrombi: incidences, cooccurrences, and epidemiological associations. Pediatr Dev Pathol. 2004;7(1):26–34. doi:10.1007/s10024-003-4032-3.
  • Waldrop LD, He Y, Hedrick TL, Rader JA. Functional morphology of gliding flight i: modeling reveals distinct performance landscapes based on soaring strategies. Integr Comp Biol. 2020;60(5):1283–96. doi:10.1093/icb/icaa114.
  • Roberts DJ, Post MD. The placenta in pre-eclampsia and intrauterine growth restriction. J Clin Pathol. 2008;61(12):1254–60. doi:10.1136/jcp.2008.055236.
  • Blair E, de Groot J, Nelson KB. Placental infarction identified by macroscopic examination and risk of cerebral palsy in infants at 35 weeks of gestational age and over. Am J Obstet Gynecol. 2011;205(2):124.e121–7. doi:10.1016/j.ajog.2011.05.022.
  • Axt R, Ertan K, Hendrik J, Wrobel M, Mink D, Schmidt W. Nucleated red blood cells in cord blood of singleton term and post-term neonates. J Perinat Med. 1999;27(5):376–81.
  • Perrone S, Vezzosi P, Longini M, Marzocchi B, Tanganelli D, Testa M, Santilli T, Buonocore G, Gruppo di Studio di Ematologia Neonatale della Società Italiana di Neonatologia. Nucleated red blood cell count in term and preterm newborns: reference values at birth. Arch Dis Child Fetal Neonatal Ed. 2005;90(2):F174–5. doi:10.1136/adc.2004.051326.
  • McCarthy JM, Capullari T, Thompson Z, Zhu Y, Spellacy WN. Umbilical cord nucleated red blood cell counts: normal values and the effect of labor. J Perinatol. 2006;26(2):89–92. doi:10.1038/sj.jp.7211437.
  • Perri T, Ferber A, Digli A, Rabizadeh E, Weissmann-Brenner A, Divon MY. Nucleated red blood cells in uncomplicated prolonged pregnancy. Obstet Gynecol. 2004;104(2):372–6. doi:10.1097/01.AOG.0000133483.94020.04.
  • Hermansen MC. Nucleated red blood cells in the fetus and newborn. Arch Dis Child Fetal Neonatal Ed. 2001;84(3):F211–5. doi:10.1136/fn.84.3.f211.
  • Redline RW. Elevated circulating fetal nucleated red blood cells and placental pathology in term infants who develop cerebral palsy. Hum Pathol. 2008;39(9):1378–84. doi:10.1016/j.humpath.2008.01.017.
  • Ferber A, Fridel Z, Weissmann-Brenner A, Minior VK, Divon MY. Are elevated fetal nucleated red blood cell counts an indirect reflection of enhanced erythropoietin activity? Am J Obstet Gynecol. 2004;190(5):1473–5. doi:10.1016/j.ajog.2004.02.033.
  • Ferber A, Minior VK, Bornstein E, Divon MY. Fetal “nonreassuring status” is associated with elevation of nucleated red blood cell counts and interleukin-6. Am J Obstet Gynecol. 2005;192(5):1427–9. doi:10.1016/j.ajog.2004.12.076.
  • Bedrick AD. Nucleated red blood cells and fetal hypoxia: a biologic marker whose ‘timing’ has come? J Perinatol. 2014;34(2):85–6. doi:10.1038/jp.2013.169.
  • Li J, Kobata K, Kamei Y, Okazaki Y, Nishihara M, Wada H, Tamai H, Funato M, Jenkin G. Nucleated red blood cell counts: an early predictor of brain injury and 2-year outcome in neonates with hypoxic-ischemic encephalopathy in the era of cooling-based treatment. Brain Dev. 2014;36(6):472–8. doi:10.1016/j.braindev.2013.06.012.
  • Boskabadi H, Zakerihamidi M, Sadeghian MH, Avan A, Ghayour-Mobarhan M, Ferns GA. Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J Matern Fetal Neonatal Med. 2017;30(21):2551–6. doi:10.1080/14767058.2016.1256988.
  • Bahr TM, Ohls RK, Baserga MC, Lawrence SM, Winter SL, Christensen RD. Implications of an elevated nucleated red blood cell count in neonates with moderate to severe hypoxic-ischemic encephalopathy. J Pediatr. 2022;246:12–8.e12. doi:10.1016/j.jpeds.2022.04.015.
  • Hutton EK, Thorpe J. Consequences of meconium stained amniotic fluid: what does the evidence tell us? Early Hum Dev. 2014;90(7):333–9. doi:10.1016/j.earlhumdev.2014.04.005.
  • Furuta N, Yaguchi C, Itoh H, Morishima Y, Tamura N, Kato M, Uchida T, Suzuki K, Sugihara K, Kawabata Y, et al. Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord. Placenta. 2012;33(1):24–30. doi:10.1016/j.placenta.2011.10.007.
  • Bekkali N, Hamers SL, Schipperus MR, Reitsma JB, Valerio PG, Van Toledo L, Benninga MA. Duration of meconium passage in preterm and term infants. Arch Dis Child Fetal Neonatal Ed. 2008;93(5):F376–9. doi:10.1136/adc.2008.138024.
  • Fanaroff AA. Meconium aspiration syndrome: historical aspects. J Perinatol. 2008;28 Suppl 3:S3–S7. doi:10.1038/jp.2008.162.
  • van Ierland Y, de Boer M, de Beaufort AJ. Meconium-stained amniotic fluid: discharge vigorous newborns. Arch Dis Child Fetal Neonatal Ed. 2010;95(1):F69–71. doi:10.1136/adc.2008.150425.
  • Oliveira CPL, Flor-de-Lima F, Rocha GMD, Machado AP, Guimaraes Pereira Areias MHF. Meconium aspiration syndrome: risk factors and predictors of severity. J Matern Fetal Neonatal Med. 2019;32(9):1492–8. doi:10.1080/14767058.2017.1410700.
  • Monen L, Hasaart TH, Kuppens SM. The aetiology of meconium-stained amniotic fluid: pathologic hypoxia or physiologic foetal ripening? Early Hum Dev. 2014;90(7):325–8. doi:10.1016/j.earlhumdev.2014.04.003.
  • Yeomans ER, Gilstrap LCIII, Leveno KJ, Burris JS. Meconium in the amniotic fluid and fetal acid-base status. Obstet Gynecol. 1989;73(2):175–8.
  • Hiersch L, Krispin E, Linder N, et al. Meconium-stained amniotic fluid and neonatal morbidity in low-risk pregnancies at term: the effect of gestational age. Am J Perinatol. 2017;34(2):183–90.
  • Rodriguez Fernandez V, Ramon Y, Ortiz EM, Naveira EC. Intrapartum and perinatal results associated with different degrees of staining of meconium stained amniotic fluid. Eur J Obstet Gynecol Reprod Biol. 2018;224:192–7. doi:10.1016/j.ejogrb.2018.03.029.
  • Altshuler G, Arizawa M, Molnar-Nadasdy G. Meconium-induced umbilical cord vascular necrosis and ulceration: a potential link between the placenta and poor pregnancy outcome. Obstet Gynecol. 1992;79(5(Pt 1)):760–6.
  • Chan JS, Baergen RN. Gross umbilical cord complications are associated with placental lesions of circulatory stasis and fetal hypoxia. Pediatr Dev Pathol. 2012;15(6):487–94. doi:10.2350/12-06-1211-OA.1.
  • Cimic A, Baergen RN. Meconium-associated umbilical vascular myonecrosis: correlations with adverse outcome and placental pathology. Pediatr Dev Pathol. 2016;19(4):315–9. doi:10.2350/15-06-1660-OA.1.
  • Grossman TB, Heller DS, Baergen RN. Isolated acute funisitis in the absence of acute chorioamnionitis: what does it mean? Placenta. 2019;75:42–4. doi:10.1016/j.placenta.2018.12.002.
  • Miller PW, Coen RW, Benirschke K. Dating the time interval from meconium passage to birth. Obstet Gynecol. 1985;66(4):459–62.
  • Funai EF, Labowsky AT, Drewes CE, Kliman HJ. Timing of fetal meconium absorption by amnionic macrophages. Am J Perinatol. 2009;26(1):93–7.
  • Incerti M, Locatelli A, Consonni S, Bono F, Leone BE, Ghidini A. Can placental histology establish the timing of meconium passage during labor? Acta Obstet Gynecol Scand. 2011;90(8):863–8. doi:10.1111/j.1600-0412.2011.01159.x.
  • Morhaime JL, Park K, Benirschke K, Baergen RN. Disappearance of meconium pigment in placental specimens on exposure to light. Arch Pathol Lab Med. 2003;127(6):711–4. doi:10.5858/2003-127-711-DOMPIP.
  • Holmgren C. Interpretation of fetal heart rate monitoring in the clinical context. Clin Obstet Gynecol. 2020;63(3):625–34. doi:10.1097/GRF.0000000000000554.
  • Ashwal E, Shinar S, Aviram A, Orbach S, Yogev Y, Hiersch L. A novel modality for intrapartum fetal heart rate monitoring. J Matern Fetal Neonatal Med. 2019;32(6):889–95. doi:10.1080/14767058.2017.1395010.
  • Faisant MC, Fontecave-Jallon J, Genoux B, Rivet B, Dia N, Resendiz M, Riethmuller D, Equy V, Hoffmann P. Non-invasive fetal monitoring: fetal heart rate multimodal estimation from abdominal electrocardiography and phonocardiography. J Gynecol Obstet Hum Reprod. 2022;51(8):102421. doi:10.1016/j.jogoh.2022.102421.
  • Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol. 2008;112(3):661–6. doi:10.1097/AOG.0b013e3181841395.
  • ACOG Practice Bulletin No. 106: intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet Gynecol. 2009;114(1):192–202.
  • Vintzileos AM, Smulian JC. Timing intrapartum management based on the evolution and duration of fetal heart rate patterns. J Matern Fetal Neonatal Med. 2022;35(25):7936–41. doi:10.1080/14767058.2021.1938531.
  • Sunsaneevithayakul P, Talungchit P, Wayuphak T, Sirisomboon R, Sompagdee N. Decision-to-delivery interval after implementation of a specific protocol for emergency cesarean delivery because of category III fetal heart rate tracings. J Obstet Gynaecol Can. 2022;44(11):1153–8. doi:10.1016/j.jogc.2022.09.001.
  • Pruksanusak N, Chainarong N, Boripan S, Geater A. Comparison of the predictive ability for perinatal acidemia in neonates between the NICHD 3-tier FHR system combined with clinical risk factors and the fetal reserve index. PLOS One. 2022;17(10):e0276451. doi:10.1371/journal.pone.0276451.
  • Jackson M, Holmgren CM, Esplin MS, Henry E, Varner MW. Frequency of fetal heart rate categories and short-term neonatal outcome. Obstet Gynecol. 2011;118(4):803–8. doi:10.1097/AOG.0b013e31822f1b50.
  • Ogunyemi D, Jovanovski A, Friedman P, Sweatman B, Madan I. Temporal and quantitative associations of electronic fetal heart rate monitoring patterns and neonatal outcomes. J Matern Fetal Neonatal Med. 2019;32(18):3115–24. doi:10.1080/14767058.2018.1456523.
  • Esplin MS. The golden hours of fetal heart rate monitoring: systematic approach to the critical times of labor and delivery. Clin Obstet Gynecol. 2020;63(3):668–77. doi:10.1097/GRF.0000000000000545.
  • Blackwell SC, Grobman WA, Antoniewicz L, Hutchinson M, Gyamfi Bannerman C. Interobserver and intraobserver reliability of the NICHD 3-tier fetal heart rate interpretation system. Am J Obstet Gynecol. 2011;205(4):378.e371–5. doi:10.1016/j.ajog.2011.06.086.
  • Clark SL, Nageotte MP, Garite TJ, Freeman RK, Miller DA, Simpson KR, Belfort MA, Dildy GA, Parer JT, Berkowitz RL, et al. Intrapartum management of category II fetal heart rate tracings: towards standardization of care. Am J Obstet Gynecol. 2013;209(2):89–97. doi:10.1016/j.ajog.2013.04.030.
  • Shields LE, Wiesner S, Klein C, Pelletreau B, Hedriana HL. A standardized approach for category II fetal heart rate with significant decelerations: maternal and neonatal outcomes. Am J Perinatol. 2018;35(14):1405–10. doi:10.1055/s-0038-1660459.
  • Eller AG, Esplin MS. Management of the category II fetal heart rate tracing. Clin Obstet Gynecol. 2020;63(3):659–67. doi:10.1097/GRF.0000000000000551.
  • Shilkurt AG, Hsu RC, Fuks AM. Fetal heart rate tracing category II: a broad category in need of stratification. Neoreviews. 2021;22(2):e88–e94.
  • Berger DS, Crosland A, Newman R, Bosse B, Makhoul J, Chan K, Seet EL. Application of a proposed algorithm to cesarean deliveries for nonreassuring fetal heart rate tracing. Am J Perinatol. 2022;39(4):342–8. doi:10.1055/s-0041-1739412.
  • Salafia CM, Silberman L. Placental pathology and abnormal fetal heart rate patterns in gestational diabetes. Pediatr Pathol. 1989;9(5):513–20. doi:10.3109/15513818909026910.
  • Salafia CM, Mangam HE, Weigl CA, Foye GJ, Silberman L. Abnormal fetal heart rate patterns and placental inflammation. Am J Obstet Gynecol. 1989;160(1):140–7. doi:10.1016/0002-9378(89)90107-5.
  • Kovo M, Schreiber L, Ben-Haroush A, Klien H, Wand S, Golan A, Bar J. Association of non-reassuring fetal heart rate and fetal acidosis with placental histopathology. Placenta. 2011;32(6):450–3. doi:10.1016/j.placenta.2011.03.006.
  • Robinson BK, Su E, Grobman W, Huang M, Ernst LM. The association of histologic placental inflammation with category II fetal heart tracings. Pediatr Dev Pathol. 2012;15(4):298–302. doi:10.2350/12-02-1158-OA.1.
  • Weiner E, Fainstein N, Schreiber L, Sagiv R, Bar J, Kovo M. The association between umbilical cord abnormalities and the development of non-reassuring fetal heart rate leading to emergent cesarean deliveries. J Perinatol. 2015;35(11):919–23. doi:10.1038/jp.2015.102.
  • Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010;86(6):329–38. doi:10.1016/j.earlhumdev.2010.05.010.
  • Dominguez-Dieppa F, Cardetti M, Rodriguez S, Garcia-Alix A, Sola A. Hypoxic-ischemic encephalopathy in units reporting to the Ibero-American Society of Neonatology Network: prevalence and mortality. MEDICC Rev. 2021;23(1):30–4.
  • Hayakawa M, Ito Y, Saito S, Mitsuda N, Hosono S, Yoda H, Cho K, Otsuki K, Ibara S, Terui K, et al. Incidence and prediction of outcome in hypoxic-ischemic encephalopathy in Japan. Pediatr Int. 2014;56(2):215–21. doi:10.1111/ped.12233.
  • Liljestrom L, Wikstrom AK, Agren J, Jonsson M. Antepartum risk factors for moderate to severe neonatal hypoxic ischemic encephalopathy: a Swedish national cohort study. Acta Obstet Gynecol Scand. 2018;97(5):615–23. doi:10.1111/aogs.13316.
  • Torn AE, Lampa E, Wikstrom AK, Jonsson M. Hypoxic ischemic encephalopathy in offspring of immigrant women in Sweden: a population-based cohort study. Acta Obstet Gynecol Scand. 2021;100(12):2285–93. doi:10.1111/aogs.14234.
  • Liljestrom L, Wikstrom AK, Jonsson M. Obstetric emergencies as antecedents to neonatal hypoxic ischemic encephalopathy, does parity matter? Acta Obstet Gynecol Scand. 2018;97(11):1396–404. doi:10.1111/aogs.13423.
  • Ugwumadu A, Arulkumaran S. A second look at intrapartum fetal surveillance and future directions. J Perinat Med. 2023;51(1):135–44. doi:10.1515/jpm-2022-0292.
  • Ravichandran L, Allen VM, Allen AC, Vincer M, Baskett TF, Woolcott CG. Incidence, intrapartum risk factors, and prognosis of neonatal hypoxic-ischemic encephalopathy among infants born at 35 weeks gestation or more. J Obstet Gynaecol Can. 2020;42(12):1489–97. doi:10.1016/j.jogc.2020.04.020.
  • Gonen N, Levy M, Kovo M, Schreiber L, Noy LK, Volpert E, Bar J, Weiner E. Placental histopathology and pregnancy outcomes in “early” vs. “late” placental abruption. Reprod Sci. 2021;28(2):351–60. doi:10.1007/s43032-020-00287-3.
  • Levy M, Gonen N, Kovo M, Schreiber L, Marom O, Barda G, Volpert E, Bar J, Weiner E. Does macroscopic estimation of the extent of placental abruption correlate with pregnancy outcomes? Eur J Obstet Gynecol Reprod Biol. 2020;254:188–94. doi:10.1016/j.ejogrb.2020.09.039.
  • Mavedatnia D, Tran J, Oltean I, et al. Impact of co-existing placental pathologies in pregnancies complicated by placental abruption and acute neonatal outcomes. J Clin Med. 2021;10(23):5693.
  • Redline RW, Roberts DJ, Parast MM, Ernst LM, Morgan TK, Greene MF, Gyamfi-Bannerman C, Louis JM, Maltepe E, Mestan KK, et al. Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease. Am J Obstet Gynecol. 2023;228(2):187–202. doi:10.1016/j.ajog.2022.08.010.
  • Turner JM, Mitchell MD, Kumar SS. The physiology of intrapartum fetal compromise at term. Am J Obstet Gynecol. 2020;222(1):17–26. doi:10.1016/j.ajog.2019.07.032.
  • Cierna Z, Varga I, Danihel LJr., Kuracinova K, Janegova A, Danihel L. Intermediate trophoblast–a distinctive, unique and often unrecognized population of trophoblastic cells. Ann Anat. 2016;204:45–50. doi:10.1016/j.aanat.2015.10.003.
  • MacLennan AH, Thompson SC, Gecz J. Cerebral palsy: causes, pathways, and the role of genetic variants. Am J Obstet Gynecol. 2015;213(6):779–88. doi:10.1016/j.ajog.2015.05.034.
  • van Eyk CL, Corbett MA, Maclennan AH. The emerging genetic landscape of cerebral palsy. Handb Clin Neurol. 2018;147:331–42.
  • Martinez-Biarge M, Diez-Sebastian J, Wusthoff CJ, Mercuri E, Cowan FM. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics. 2013;132(4):e952–959. doi:10.1542/peds.2013-0511.
  • Aslam S, Strickland T, Molloy EJ. Neonatal encephalopathy: need for recognition of multiple etiologies for optimal management. Front Pediatr. 2019;7:142. doi:10.3389/fped.2019.00142.
  • Ostrander B, Bale JF. Congenital and perinatal infections. Handb Clin Neurol. 2019;162:133–53.
  • Costa ML, de Moraes Nobrega G, Antolini-Tavares A. Key infections in the placenta. Obstet Gynecol Clin North Am. 2020;47(1):133–46. doi:10.1016/j.ogc.2019.10.003.
  • Rees S, Inder T. Fetal and neonatal origins of altered brain development. Early Hum Dev. 2005;81(9):753–61. doi:10.1016/j.earlhumdev.2005.07.004.
  • Rees S, Harding R, Walker D. An adverse intrauterine environment: implications for injury and altered development of the brain. Int J Dev Neurosci. 2008;26(1):3–11. doi:10.1016/j.ijdevneu.2007.08.020.
  • Giovannini E, Bonasoni MP, Pascali JP, Giorgetti A, Pelletti G, Gargano G, Pelotti S, Fais P. Infection induced fetal inflammatory response syndrome (FIRS): state-of-the-art and medico-legal implications-a narrative review. Microorganisms. 2023;11(4):1010. doi:10.3390/microorganisms11041010.
  • Melamed N, Baschat A, Yinon Y, Athanasiadis A, Mecacci F, Figueras F, Berghella V, Nazareth A, Tahlak M, McIntyre HD, et al. FIGO (International Federation of Gynecology and Obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynaecol Obstet. 2021;152 Suppl 1(Suppl 1):3–57. doi:10.1002/ijgo.13522.
  • Pineles BL, Mendez-Figueroa H, Chauhan SP. Diagnosis of fetal growth restriction in a cohort of small-for-gestational-age neonates at term: neonatal and maternal outcomes. Am J Obstet Gynecol MFM. 2022;4(5):100672. doi:10.1016/j.ajogmf.2022.100672.
  • Al-Shargabi T, Govindan RB, Dave R, Metzler M, Wang Y, Du Plessis A, Massaro AN. Inflammatory cytokine response and reduced heart rate variability in newborns with hypoxic-ischemic encephalopathy. J Perinatol. 2017;37(6):668–72. doi:10.1038/jp.2017.15.
  • Scher MS. Neurologic outcome after fetal inflammatory response syndrome: trimester-specific considerations. Semin Fetal Neonatal Med. 2020;25(4):101137. doi:10.1016/j.siny.2020.101137.
  • Tan S. Fault and blame, insults to the perinatal brain may be remote from time of birth. Clin Perinatol. 2014;41(1):105–17. doi:10.1016/j.clp.2013.10.006.

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