Am J Perinatol 2019; 36(01): 027-033
DOI: 10.1055/s-0038-1639356
SMFM Fellowship Series Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Risk Factors for Neonatal Hypoxic-Ischemic Encephalopathy in the Absence of Sentinel Events

Christopher M. Novak
1   Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
,
Ahize C. Eke
1   Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
,
Maide Ozen
2   Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
3   Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
,
Irina Burd
1   Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
3   Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
4   Neuroscience Intensive Care Nursery Program, Johns Hopkins University School of Medicine, Baltimore, Maryland
5   Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
,
Ernest M. Graham
1   Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
4   Neuroscience Intensive Care Nursery Program, Johns Hopkins University School of Medicine, Baltimore, Maryland
› Author Affiliations
Funding E.M.G. is supported by NICHD grant R01HD086058.
Further Information

Publication History

13 October 2017

12 February 2018

Publication Date:
26 March 2018 (online)

Abstract

Objective Hypoxic-ischemic encephalopathy (HIE) may be associated with intrapartum sentinel events or may be unexplained. We sought to identify risk factors for unexplained HIE cases and compare their morbidity and mortality to cases associated with sentinel events.

Study Design Retrospective cohort study of all neonates admitted with suspected HIE treated with whole-body hypothermia from January 2007 through July 2017. Cases of unexplained HIE were compared with those with a sentinel event.

Results A total of 223 neonates met the inclusion criteria, of which 86 (38.6%) experienced a sentinel event and 137 (61.4%) did not. Placental histopathology was performed for 28/31 (90.3%) and 48/53 (90.6%) inborn neonates with and without sentinel events, respectively. Placentas from unexplained HIE cases more often exhibited histologic chorioamnionitis (43.8% vs. 17.9%, p = 0.02) and funisitis (25% vs. 3.6%, p = 0.02). Neonatal morbidity and mortality were similar. On multivariable regression, nulliparity (odds ratio [OR], 4.11, 95% confidence interval [CI]: 1.24–13.62) and histologic funisitis (OR, 20.33, 95% CI: 1.11–373.4) remained significant.

Conclusion Other than nulliparity and infection which could be identified on umbilical cord examination following delivery but not on clinical assessment prior to delivery, there are no other identifiable risk factors for HIE in the absence of a sentinel event, and morbidity and mortality are similar between groups.

 
  • References

  • 1 Authors N. 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
  • 2 Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 329-338
  • 3 Graham EM, Ruis KA, Hartman AL, Northington FJ, Fox HE. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199 (06) 587-595
  • 4 Martinez-Biarge M, Madero R, González A, Quero J, García-Alix A. Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associated with intrapartum sentinel events. Am J Obstet Gynecol 2012; 206 (02) 148.e1-148.e7
  • 5 Spain JE, Tuuli MG, Macones GA, Roehl KA, Odibo AO, Cahill AG. Risk factors for serious morbidity in term nonanomalous neonates. Am J Obstet Gynecol 2015; 212 (06) 799.e1-799.e7
  • 6 Frey HA, Tuuli MG, Shanks AL, Macones GA, Cahill AG. Interpreting category II fetal heart rate tracings: does meconium matter?. Am J Obstet Gynecol 2014; 211 (06) 644.e1-644.e8
  • 7 Blume HK, Li CI, Loch CM, Koepsell TD. Intrapartum fever and chorioamnionitis as risks for encephalopathy in term newborns: a case-control study. Dev Med Child Neurol 2008; 50 (01) 19-24
  • 8 Eklind S, Mallard C, Leverin AL. , et al. Bacterial endotoxin sensitizes the immature brain to hypoxic--ischaemic injury. Eur J Neurosci 2001; 13 (06) 1101-1106
  • 9 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
  • 10 Shankaran S, Laptook AR, Ehrenkranz RA. , et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
  • 11 Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991; 181 (01) 129-133
  • 12 Fern R, Möller T. Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci 2000; 20 (01) 34-42
  • 13 Galluzzi L, Blomgren K, Kroemer G. Mitochondrial membrane permeabilization in neuronal injury. Nat Rev Neurosci 2009; 10 (07) 481-494
  • 14 Giulian D, Vaca K. Inflammatory glia mediate delayed neuronal damage after ischemia in the central nervous system. Stroke 1993; 24 (12, Suppl): I84-I90
  • 15 Eklind S, Mallard C, Arvidsson P, Hagberg H. Lipopolysaccharide induces both a primary and a secondary phase of sensitization in the developing rat brain. Pediatr Res 2005; 58 (01) 112-116
  • 16 Impey LWM, Greenwood CEL, Black RS, Yeh PS-Y, Sheil O, Doyle P. The relationship between intrapartum maternal fever and neonatal acidosis as risk factors for neonatal encephalopathy. Am J Obstet Gynecol 2008; 198 (01) 49.e1-49.e6
  • 17 Castillo J. Deteriorating stroke: diagnostic criteria, predictors, mechanisms and treatment. Cerebrovasc Dis 1999; 9 (Suppl 3): 1-8
  • 18 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 (05) 449-476
  • 19 Sills A, Steigman C, Ounpraseuth ST, Odibo I, Sandlin AT, Magann EF. Pathologic examination of the placenta: recommended versus observed practice in a university hospital. Int J Womens Health 2013; 5: 309-312
  • 20 Curtin WM, Krauss S, Metlay LA, Katzman PJ. Pathologic examination of the placenta and observed practice. Obstet Gynecol 2007; 109 (01) 35-41
  • 21 Badawi N, Kurinczuk JJ, Keogh JM, Chambers HM, Stanley FJ. Why is the placenta being ignored?. Aust N Z J Obstet Gynaecol 2000; 40 (03) 343-346
  • 22 Shi Z, Ma L, Luo K. , et al. Chorioamnionitis in the development of cerebral palsy: a meta-analysis and systematic review. Pediatrics 2017; 139 (06) e20163781
  • 23 Higgins RD, Saade G, Polin RA. , et al; Chorioamnionitis Workshop Participants. Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: summary of a workshop. Obstet Gynecol 2016; 127 (03) 426-436
  • 24 Romero R, Chaemsaithong P, Korzeniewski SJ. , et al. Clinical chorioamnionitis at term III: how well do clinical criteria perform in the identification of proven intra-amniotic infection?. J Perinat Med 2016; 44 (01) 23-32
  • 25 Towers CV, Yates A, Zite N, Smith C, Chernicky L, Howard B. Incidence of fever in labor and risk of neonatal sepsis. Am J Obstet Gynecol 2017; 216 (06) 596.e1-596.e5
  • 26 Lau J, Magee F, Qiu Z, Houbé J, Von Dadelszen P, Lee SK. Chorioamnionitis with a fetal inflammatory response is associated with higher neonatal mortality, morbidity, and resource use than chorioamnionitis displaying a maternal inflammatory response only. Am J Obstet Gynecol 2005; 193 (3 Pt 1): 708-713
  • 27 Tann CJ, Nakakeeto M, Willey BA. , et al. Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study. Arch Dis Child Fetal Neonatal Ed 2017 Doi: 10.1136/archdischild-2017-312744
  • 28 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 (06) 849.e1-849.e7
  • 29 Grobman WA, Bailit J, Lai Y. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Association of the duration of active pushing with obstetric outcomes. Obstet Gynecol 2016; 127 (04) 667-673
  • 30 Rouse DJ, Weiner SJ, Bloom SL. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Second-stage labor duration in nulliparous women: relationship to maternal and perinatal outcomes. Am J Obstet Gynecol 2009; 201 (04) 357.e1-357.e7
  • 31 Contag SA, Clifton RG, Bloom SL. , et al. Neonatal outcomes and operative vaginal delivery versus cesarean delivery. Am J Perinatol 2010; 27 (06) 493-499
  • 32 Rouse DJ, Weiner SJ, Bloom SL. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Failed labor induction: toward an objective diagnosis. Obstet Gynecol 2011; 117 (2 Pt 1): 267-272
  • 33 Graham EM, Burd I, Everett AD, Northington FJ. Blood biomarkers for evaluation of perinatal encephalopathy. Front Pharmacol 2016; 7: 196