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Am J Perinatol 2019; 36(08): 828-834
DOI: 10.1055/s-0038-1675329
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Maternal Epidural Steroids to Prevent Neonatal Exposure to Hyperthermia and Inflammation

Christopher Goodier
1   Department of Maternal-Fetal Medicine, Medical University of South Carolina, Charleston, South Carolina
,
Roger Newman
1   Department of Maternal-Fetal Medicine, Medical University of South Carolina, Charleston, South Carolina
,
Latha Hebbar
2   Department of Anesthesiology, Medical University of South Carolina, Charleston, South Carolina
,
Julie Ross
3   Department of Neonatology, Medical University of South Carolina, Charleston, South Carolina
,
Cynthia Schandl
4   Department of Pathology, Medical University of South Carolina, Charleston, South Carolina
,
Laura Goetzl
5   Department of Maternal-Fetal Medicine, University of Texas Health Science Center, Houston, Texas
› Author Affiliations Funding This study was funded by the Department of OBGYN Center for Women's Health Research and Research Development Fund. In addition, the project described was supported by the NIH National Center for Advancing Translational Sciences (NCATS) through Grant Number UL1 TR001450.
Further Information

Publication History

21 September 2017

15 September 2018

Publication Date:
02 November 2018 (online)

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Abstract

Background Epidural analgesia is associated with a fourfold increased rate of intrapartum fever. The likely pathophysiology is a noninfectious maternal inflammatory activation. Safe interventions to reduce maternal and neonatal exposures to intrapartum fever and inflammation are needed.

Objective The purpose of this study was to determine if prophylactic epidural steroids decrease fetal exposure to hyperthermia and inflammatory cytokines following epidural analgesia.

Study Design This is a randomized, double-blinded, placebo controlled trial. Term nulliparous women requesting epidural analgesia received 80 mg methylprednisolone or preservative-free normal saline via the epidural catheter at placement. The primary outcome was maternal temperature >100.4°F. Secondary outcomes included fetal exposure to inflammation as assessed by cord blood interleukin-6 (IL-6) levels and rates of funisitis. Power analysis estimated a sample size requirement of 276, but new Food and Drug Administration (FDA) recommendations advising a black box warning on epidural steroids resulted in early study termination.

Results A total of 116 subjects were enrolled: 58 treatments and 58 placebos. There was no difference in the rate of maternal intrapartum fever or cord blood IL-6 levels between treatment arms. No complications listed in the FDA warning occurred.

Conclusion Prophylactic epidural methylprednisolone was not effective in reducing intrapartum fever or neonatal inflammation following epidural analgesia. Alternate mechanisms and preventative strategies should be considered.

Keywords

epidural analgesia - maternal fever - chorioamnionitis - inflammation - steroids - labor - funisitis

Condensation

Prophylactic epidural methylprednisolone was not effective in reducing intrapartum fever or neonatal inflammation following epidural analgesia.


Note

These findings were presented as poster at the 35th SMFM Annual Meeting—The Pregnancy Meeting. February 2–7, 2015, San Diego, CA. This study was registered at www.ClinicalTrials.gov (NCT02212210).


 

  • References

  • 1 Fusi L, Steer PJ, Maresh MJ, Beard RW. Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet 1989; 1 (8649): 1250-1252
    PubMedGoogle Scholar
  • 2 Sharma SK, Alexander JM, Messick G. , et al. Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women. Anesthesiology 2002; 96 (03) 546-551
    CrossrefPubMedGoogle Scholar
  • 3 Lucas MJ, Sharma SK, McIntire DD. , et al. A randomized trial of labor analgesia in women with pregnancy-induced hypertension. Am J Obstet Gynecol 2001; 185 (04) 970-975
    CrossrefPubMedGoogle Scholar
  • 4 Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol 1995; 86 (05) 783-789
    CrossrefPubMedGoogle Scholar
  • 5 Goetzl L, Evans T, Rivers J, Suresh MS, Lieberman E. Elevated maternal and fetal serum interleukin-6 levels are associated with epidural fever. Am J Obstet Gynecol 2002; 187 (04) 834-838
    CrossrefPubMedGoogle Scholar
  • 6 Goetzl L, Rivers J, Zighelboim I, Wali A, Badell M, Suresh MS. Intrapartum epidural analgesia and maternal temperature regulation. Obstet Gynecol 2007; 109 (03) 687-690
    CrossrefPubMedGoogle Scholar
  • 7 Riley LE, Celi AC, Onderdonk AB. , et al. Association of epidural-related fever and noninfectious inflammation in term labor. Obstet Gynecol 2011; 117 (03) 588-595
    CrossrefPubMedGoogle Scholar
  • 8 Sharma SK, Rogers BB, Alexander JM, McIntire DD, Leveno KJ. A randomized trial of the effects of antibiotic prophylaxis on epidural-related fever in labor. Anesth Analg 2014; 118 (03) 604-610
    CrossrefPubMedGoogle Scholar
  • 9 Goetzl L, Rivers J, Evans T. , et al. Prophylactic acetaminophen does not prevent epidural fever in nulliparous women: a double-blind placebo-controlled trial. J Perinatol 2004; 24 (08) 471-475
    CrossrefPubMedGoogle Scholar
  • 10 Lavesson T, Åkerman F, Källén K, Olofsson P. Effects on fetal and maternal temperatures of paracetamol administration during labour: a case-control study. Eur J Obstet Gynecol Reprod Biol 2013; 168 (02) 138-144
    CrossrefPubMedGoogle Scholar
  • 11 Goetzl L, Zighelboim I, Badell M. , et al. Maternal corticosteroids to prevent intrauterine exposure to hyperthermia and inflammation: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol 2006; 195 (04) 1031-1037
    CrossrefPubMedGoogle Scholar
  • 12 Wang LZ, Hu XX, Liu X, Qian P, Ge JM, Tang BL. Influence of epidural dexamethasone on maternal temperature and serum cytokine concentration after labor epidural analgesia. Int J Gynaecol Obstet 2011; 113 (01) 40-43
    CrossrefPubMedGoogle Scholar
  • 13 Kim D, Brown J. Efficacy and safety of lumbar epidural dexamethasone versus methylprednisolone in the treatment of lumbar radiculopathy: a comparison of soluble versus particulate steroids. Clin J Pain 2011; 27 (06) 518-522
    CrossrefPubMedGoogle Scholar
  • 14 Kushnerik V, Altman G, Gozenput P. Pharmacology of steroids used during epidural steroid injections. Tech Reg Anesth Pain Manage 2009; 13 (04) 212-216
    PubMedGoogle Scholar
  • 15 Keck JF, Gerkensmeyer JE, Joyce BA, Schade JG. Reliability and validity of the Faces and Word Descriptor Scales to measure procedural pain. J Pediatr Nurs 1996; 11 (06) 368-374
    CrossrefPubMedGoogle Scholar
  • 16 Redline RW. Inflammatory response in acute chorioamnionitis. Semin Fetal Neonatal Med 2012; 17 (01) 20-25
    CrossrefPubMedGoogle Scholar
  • 17 Racoosin JA, Seymour SM, Cascio L, Gill R. Serious neurologic events after epidural glucocorticoid injection--the FDAs risk assessment. N Engl J Med 2015; 373 (24) 2299-2301
    CrossrefPubMedGoogle Scholar
  • 18 Lieberman E, Lang JM, Frigoletto Jr F, Richardson DK, Ringer SA, Cohen A. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 1997; 99 (03) 415-419
    CrossrefPubMedGoogle Scholar
  • 19 Yancey MK, Zhang J, Schwarz J, Dietrich III CS, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol 2001; 98 (5 Pt 1): 763-770
    PubMedGoogle Scholar
  • 20 Goetzl L, Cohen A, Frigoletto Jr F, Lang JM, Lieberman E. Maternal epidural analgesia and rates of maternal antibiotic treatment in a low-risk nulliparous population. J Perinatol 2003; 23 (06) 457-461
    CrossrefPubMedGoogle Scholar
  • 21 Kendall G, Peebles D. Acute fetal hypoxia: the modulating effect of infection. Early Hum Dev 2005; 81 (01) 27-34
    CrossrefPubMedGoogle Scholar
  • 22 Impey L, Greenwood C, MacQuillan K, Reynolds M, Sheil O. Fever in labour and neonatal encephalopathy: a prospective cohort study. BJOG 2001; 108 (06) 594-597
    PubMedGoogle Scholar
  • 23 Impey LW, Greenwood CE, Black RS, Yeh PS, 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
    CrossrefPubMedGoogle Scholar
  • 24 Goetzl L, Korte JE. Interaction between intrapartum maternal fever and fetal acidosis increases risk for neonatal encephalopathy. Am J Obstet Gynecol 2008; 199 (02) e9
    PubMedGoogle Scholar
  • 25 Weissmann G, Korchak H, Ludewig R. , et al. Non-steroidal anti-inflammatory drugs: how do they work?. Eur J Rheumatol Inflamm 1987; 8 (01) 6-17
    PubMedGoogle Scholar
  • 26 Schorr SJ, Ascarelli MH, Rust OA. , et al. A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. South Med J 1998; 91 (11) 1028-1032
    CrossrefPubMedGoogle Scholar
  • 27 Van den Veyver IB, Moise Jr KJ. Prostaglandin synthetase inhibitors in pregnancy. Obstet Gynecol Surv 1993; 48 (07) 493-502
    CrossrefPubMedGoogle Scholar
  • 28 Broadman LM. Non-steroidal anti-inflammatory drugs, antiplatelet medications and spinal axis anesthesia. Best Pract Res Clin Anaesthesiol 2005; 19 (01) 47-58
    CrossrefPubMedGoogle Scholar
  • 29 Bronson SL, Bale TL. Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal antiinflammatory treatment. Endocrinology 2014; 155 (07) 2635-2646
    CrossrefPubMedGoogle Scholar