Pediatric Drugs

, Volume 5, Issue 9, pp 615–627 | Cite as

Effects of Obstetric Analgesics and Anesthetics on the Neonate

A Review
  • Jay E. Mattingly
  • John D’Alessio
  • Jaya RamanathanEmail author
Review Article


Most anesthetic and analgesic agents in current use traverse the placental barrier in varying degrees, but are well tolerated by the fetus if judiciously administered. For labor analgesia, many options are available. Systemic administration of opioids and sedatives is one such option. Repeated maternal administration of opioids such as pethidine (meperidine) results in significant fetal exposure and neonatal respiratory depression. Patient-controlled analgesia with synthetic opioids such as fentanyl, alfentanil, and the new ultra-short-acting remifentanil may be used for labor analgesia in selected patients.

Other options for labor analgesia include epidural and combined spinal-epidural techniques. With such techniques, neonatal exposure to opioids and sedatives can be minimized or totally avoided. While limiting the fetal exposure to the harmful effects of depressant drugs, epidural anesthesia and/or analgesia improves placental perfusion and oxygenation of the fetus, which is beneficial, especially in conditions such as pregnancy-induced hypertension. Regional blocks are also administered for the majority of cesarean deliveries because of the overwhelming and unequivocal evidence of maternal and fetal safety compared with general anesthesia for this indication. However, in some instances, administration of general anesthesia is unavoidable. Neonatal respiratory depression with low Apgar scores, and umbilical arterial and venous pH associated with general anesthesia, is often transient. A properly administered anesthetic, whether regional or general, has no significant adverse fetal or neonatal effects.


Remifentanil Epidural Analgesia Alfentanil Etomidate Desflurane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to gratefully acknowledge the assistance of Nannette Wells-Brooks, CRNA, and David M. Armbruster, PhD, in the preparation of this manuscript.

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.


  1. 1.
    Pacifici GM, Nottoli R. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 1995; 28: 235–69PubMedCrossRefGoogle Scholar
  2. 2.
    Low JA, Wood SI, Killen HL, et al. Intrapartum asphyxia in the preterm fetus <2000 gm. Am J Obstet Gynecol 1990; 162: 378–82PubMedGoogle Scholar
  3. 3.
    Malinow AM, Dailey PA. Anesthesia for preterm labor and delivery. In: Hughes SC, Levinson G, Rosen MA, editors. Anesthesia for obstetrics. Philadelphia (PA): Lippincott Williams and Wilkins, 2002: 323–34Google Scholar
  4. 4.
    Morishima HO, Pedersen H, Santos AC, et al. Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb. Anesthesiology 1989; 71: 110–5PubMedCrossRefGoogle Scholar
  5. 5.
    Morishima HO, Santos AC, Pedersen H, et al. Effects of lidocaine on the asphyxial responses in the mature fetal lamb. Anesthesiology 1987; 66: 502–7PubMedCrossRefGoogle Scholar
  6. 6.
    Teramo K, Benowitz N, Heymann MA, et al. Effects of lidocaine on heart rate, blood pressure and electrocorticogram in fetal sheep. Am J Obstet Gynecol 1974; 118: 935–49PubMedGoogle Scholar
  7. 7.
    Pedersen H, Santos AC, Morishima HO, et al. Does gestational age affect the pharmacokinetics and pharmacodynamics of lidocaine in mother and fetus? Anesthesiology 1988; 68: 367–72PubMedCrossRefGoogle Scholar
  8. 8.
    Kuhnert BR, Philipson EM, Kuhnert PM, et al. Disposition of meperidine and normeperidine following multiple doses during labor (II): fetus and neonate. Am J Obstet Gynecol 1985; 151: 410–5PubMedGoogle Scholar
  9. 9.
    Beitrage P, Boreus LO, Harvig P, et al. Neonatal depression after obstetric analgesia with pethidine: the role of the injection delivery time interval and of the plasma concentration of pethidine and norpethidine. Acta Obstet Gynaecol Scand 1981; 60: 43–9CrossRefGoogle Scholar
  10. 10.
    Clark RB, Seifan AB. Systemic medications during labor and delivery. Obstet Gynecol Annu 1983; 12: 165–97PubMedGoogle Scholar
  11. 11.
    Nordberg G, Hedner T, Mellstrand T, et al. Pharmacokinetic aspects of intrathecal morphine analgesia. Anesthesiology 1984; 60: 448–64PubMedCrossRefGoogle Scholar
  12. 12.
    Nikkola EM, Ekblad UU, Keri PO, et al. Intravenous fentanyl PCA during labor. Can J Anaesth 1997; 44: 1248–55PubMedCrossRefGoogle Scholar
  13. 13.
    Morley-Forster PK, Weberpals J. Neonatal effects of patient controlled analgesia using fentanyl in labor. Int J Obstet Anaesth 1998; 7: 105–7CrossRefGoogle Scholar
  14. 14.
    Cartwight DP, Dann WL, Hutchinson A. Placental transfer of alfentanil at caesarean section. Eur J Aneasth 1989; 6: 103–10Google Scholar
  15. 15.
    Gin T, Ngan Kee WD, Siu YK, et al. Alfentanil given immediately before the induction of anesthesia for elective cesarean delivery. Anesthesiology 2000; 90: 1167–72Google Scholar
  16. 16.
    Morley-Forster P, Reid DW, Vandeberghe H. A comparison of patient-controlled analgesia fentanyl and alfentanil for labor analgesia. Can J Anesth 2000; 47: 113–9PubMedCrossRefGoogle Scholar
  17. 17.
    Dilger JA, Waters JH, Tetzlaff JE. Remifentanil for labor analgesia. Am J Anesthesiol 2000; 27: 553–4Google Scholar
  18. 18.
    Roclants F, De Franceschi E, Veyckemans F, et al. Patient-controlled intravenous analgesia using remifentanil in the parturient. Can J Anaesth 2001; 48: 175–8CrossRefGoogle Scholar
  19. 19.
    Volmanen P, Akural E, Raudaskoski T, et al. Remifentanil in obstetric analgesia: a dose-finding study. Anesth Analg 2002; 94: 913–7PubMedCrossRefGoogle Scholar
  20. 20.
    Maduska AL, Hajgassemali M. Double-blind comparison of butorphanol and meperidine in labor: maternal pain relief and the effect on the newborn. Can Anaesth Soc J 1978; 25: 398–404PubMedCrossRefGoogle Scholar
  21. 21.
    McAteer MFE, Cattermile R, Loughnan B, et al. Nalbuphine for obstetric analgesia. Anaesthesia 1987; 42: 697–703PubMedCrossRefGoogle Scholar
  22. 22.
    Levy BT, Dawson JD, Toth PP, et al. Predictors of neonatal resuscitation, low Apgar scores, and umbilical artery pH among growth-restricted neonates. Obstet Gynecol 1998 Jun; 91(6): 909–16PubMedCrossRefGoogle Scholar
  23. 23.
    Pinkofsky HB. Effects of antipsychotics on the unborn child: what is known and how should this influence prescribing? Paediatr Drugs 2000; 2(2): 83–90PubMedGoogle Scholar
  24. 24.
    McAllister CB. Placental transfer and neonatal effects of diazepam when administered to the mother just before delivery. Br J Anaesth 1980; 52: 423–7PubMedCrossRefGoogle Scholar
  25. 25.
    Bach V, Carl P, Ravlo O, et al. A randomized comparison between midazolam and thiopental for elective cesarean section: placental transfer and elimination in the neonate. Anesth Analg 1989; 68: 238–42PubMedCrossRefGoogle Scholar
  26. 26.
    Santos A, Karpel B, Noble G. The placental transfer and fetal effects of levobupi-vacaine, racemic bupivacaine, and ropivacaine. Anesthesiology 1999; 90: 1698–703PubMedCrossRefGoogle Scholar
  27. 27.
    Johnson RF, Cahana A, Olenick M, et al. A comparison of the placental transfer of ropivacaine versus bupivacaine. Anesth Analg 1999; 89: 703–8PubMedGoogle Scholar
  28. 28.
    Ala-Kokko TI, Pienimaki P, Herva R, et al. Transfer of lidocaine and bupivacaine, across the isolated perfused human placenta. Pharmacol Toxicol 1995; 77: 142–8PubMedCrossRefGoogle Scholar
  29. 29.
    Kuhnert B, Kuhnert P, Prochaska A. Plasma levels of 2-chloroprocaine in obstetric patients and their neonates after epidural anesthesia. Anesthesiology 1981; 53: 21–5CrossRefGoogle Scholar
  30. 30.
    Bader AM, Fragneto R, Terui K, et al. Maternal and neonatal fentanyl and bupivacaine concentrations after epidural infusion during labor. Anesth Analg 1995; 81: 829–32PubMedGoogle Scholar
  31. 31.
    Loftus J, Hill H, Cohen S. Placental transfer and neonatal effects of epidural sufentanil and fentanyl administered with bupivacaine during labor. Anesthesiology 1995; 83: 300–8PubMedCrossRefGoogle Scholar
  32. 32.
    Jouppila R, Jouppila P, Hollmen A, et al. Effect of segmental extradural analgesia on placental blood flow during normal labour. Br J Anaesth 1978; 50: 563–7PubMedCrossRefGoogle Scholar
  33. 33.
    Hollman A, Jouppila R, Jouppila P. Effect of extradural analgesia using bupivacaine and 2-chloroprocaine on intervillous blood flow during normal labour. Br J Anaesth 1982; 54: 837–41CrossRefGoogle Scholar
  34. 34.
    Marx GF, Patel S, Berman JA, et al. Umbilical blood flow velocity waveforms in different maternal positions and with epidural analgesia. Obstet Gynecol 1986; 68: 61–4PubMedGoogle Scholar
  35. 35.
    Brizgys RV, Dailey PA, Shnider SM, et al. The incidence and neonatal effects of maternal hypotension during epidural anesthesia for cesarean section. Anesthesiology 1987; 67: 782–6PubMedCrossRefGoogle Scholar
  36. 36.
    Chestnut DH, Bates JN, Choi WW. Effect of intravenous administration of Ringer’s lactate on maternal capillary blood glucose before elective cesarean section. J Reprod Med 1987 Mar; 32(3): 191–3PubMedGoogle Scholar
  37. 37.
    Roberts SW, Leveno KJ, Sidawi JE, et al. Fetal acidemia associated with regional anesthesia for elective cesarean delivery. Obstet Gynecol 1995; 85: 79–83PubMedCrossRefGoogle Scholar
  38. 38.
    Mueller MD, Bruhwiler H, Schupfer GK, et al. Higher rate of fetal acidemia after regional anesthesia for elective cesarean delivery. Obstet Gynecol 1997; 90: 131–4PubMedCrossRefGoogle Scholar
  39. 39.
    Siddik SM, Aouad MT, Kai GE, et al. Hydroxyethylstarch 10% is superior to Ringer’s solution for preloading before spinal anesthesia for cesarean section. Can J Anaesth 2000 Jul; 47(7): 607–10CrossRefGoogle Scholar
  40. 40.
    Philipson EH, Kalhan SC, Riha MM, et al. Effects of maternal glucose infusion on fetal acid-base status in human pregnancy. Am J Obstet Gynecol 1987; 157: 866–73PubMedGoogle Scholar
  41. 41.
    Kangas-Saarela T, Hollmen A, Tolonen U, et al. Does ephedrine influence newborn neurobehavorial responses and spectral EEG when used to prevent maternal hypotension during caesarean section? Acta Anaesthesiol Scand 1990; 34: 8–16PubMedCrossRefGoogle Scholar
  42. 42.
    Shearer VE, Ramin SM, Wallace DH, et al. Fetal effects of prophylactic ephedrine and maternal hypotension during regional anesthesia for cesarean section. J Matern Fetal Med 1996; 5: 79–84PubMedCrossRefGoogle Scholar
  43. 43.
    LaPorta R, Arthur G, Datta S. Phenylephrine in treating maternal hypotension due to spinal anesthesia for cesarean delivery: effects on neonatal catecholamine concentrations, acid base status and Apgar scores. Acta Anaesthesiol Scand 1995; 39: 901–5PubMedCrossRefGoogle Scholar
  44. 44.
    Scanlon J, Brown W, Weiss J, et al. Neurobehavioral responses of newborn infants after maternal epidural anesthesia. Anesthesiology 1978; 40: 121–8CrossRefGoogle Scholar
  45. 45.
    Kangas-Saarela T, Jouppila R, Alahuhta S, et al. The effect of lumbar epidural analgesia on the neurobehavorial responses of newborn infants. Acta Anaesthesiol Scand 1989; 33: 320–5PubMedCrossRefGoogle Scholar
  46. 46.
    Brockhurst NJ, Littleford JA, Halpern SH. The neurologic and adaptive capacity scores. Anesthesiology 2000; 92: 237–46PubMedCrossRefGoogle Scholar
  47. 47.
    Gambling DR, Sharma SK, Ramin SM, et al. A randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor. Anesthesiology 1998; 89: 1336–44PubMedCrossRefGoogle Scholar
  48. 48.
    DeVelde MV, Vercauteren M, Vandermeersch E. Fetal heart rate abnormalities after regional analgesia for labor pain: the effects of intrathecal opioids. Reg Anesth Pain Med 2001; 26: 257–62Google Scholar
  49. 49.
    Fusi L, Maresh MJA, Steer PJ, et al. Maternal pyrexia associated with the use of epidural analgesia in labor. Lancet 1989; I: 1250–2CrossRefGoogle Scholar
  50. 50.
    Camann WR, Hortvert LA, Hughes N, et al. Maternal temperature regulation during extradural analgesia for labor. Br J Anaesth 1991; 67: 565–8PubMedCrossRefGoogle Scholar
  51. 51.
    Macaulay JH, Bond K, Steer OJ. Epidural analgesia in labor and fetal hyperthermia. Obstet Gynecol 1992; 80: 665–9PubMedGoogle Scholar
  52. 52.
    Mayer DC, Chescheir NC, Speilman FJ. Increased intrapartum antibiotic administration associated with epidural analgesia in labor. Am J Perinatol 1997; 14: 83–6PubMedCrossRefGoogle Scholar
  53. 53.
    Lieberman E, Lang JM, Frigoletto Jr FJ, et al. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 1997 Mar; 99(3): 415–9PubMedCrossRefGoogle Scholar
  54. 54.
    Philip J, Alexander J, Sharma S, et al. Epidural analgesia during labor and maternal fever. Anesthesiology 1999; 90: 1271–5PubMedCrossRefGoogle Scholar
  55. 55.
    Viscomi CM, Manullang T. Maternal fever, neonatal sepsis evaluation, and epidural labor analgesia: review article. Reg Anesth Pain Med 2000 Sep#–Oct; 25(5): 549–53PubMedGoogle Scholar
  56. 56.
    Datta S, Ostheimer GW, Weiss JB, et al. Neonatal effects of prolonged anesthetic induction. Obstet Gynecol 1981; 58: 331–5PubMedGoogle Scholar
  57. 57.
    Crawford JS, James III FM, Crawley M. A further study of general anesthesia for caesarean section. Br J Anaesth 1976; 48: 661–7PubMedCrossRefGoogle Scholar
  58. 58.
    Gasparoni A, Ciardelli L, De Amici D, et al. Effect of general and epidural anaesthesia on thyroid hormones and immunity in neonates. Paediatr Anaesth 2002 Jan; 12(1): 59–64PubMedCrossRefGoogle Scholar
  59. 59.
    Kosaka Y, Takahashi T, Mark L. Intravenous thiobarbiturate anesthesia for cesarean section. Anesthesiology 1969; 31: 489–506PubMedCrossRefGoogle Scholar
  60. 60.
    Ellison A, Haram K, Sagen N, et al. Transplacental passage of ketamine after intravenous administration. Acta Aneasth Scand 1977; 21: 41–4CrossRefGoogle Scholar
  61. 61.
    Crozier T, Flamm C, Speer C, et al. Effects of etomidate on the adrenocortical and metabolic adaptation of the neonate. Br J Anaesth 1993; 70: 47–53PubMedCrossRefGoogle Scholar
  62. 62.
    Reddy B, Pizer B, Bull P. Neonatal serum cortisol suppression by etomidate compared with thiopentone, for elective caesarean section. Eur J Anaesthiol 1988; 5: 171–6Google Scholar
  63. 63.
    Abboud TK, Zhu J, Richards M, et al. Intravenous propofol vs thiamylal-isoflurane for caesarean section: comparative maternal and neonatal effects. Acta Anaesthesiol Scand 1995; 39: 205–9PubMedCrossRefGoogle Scholar
  64. 64.
    Celleno D, Capogna G, Tomassetti M, et al. Neurobehavorial effects of propofol on the neonate following elective caesarean section. Br J Anaesth 1989; 62: 649–54PubMedCrossRefGoogle Scholar
  65. 65.
    Tomioko S, Nakajo N. No genotoxic effects of propofol in Chinese hamster ovary cells: analysis by sister chromatid exchanges. Acta Anaesth Scand 1999; 43: 1261–5Google Scholar
  66. 66.
    Ramanathan J, D’Alessio J, Geller E, et al. Analgesia and anesthesia during pregnancy. In: Elkayam U, Gleicher G, editors. Cardiac problems in pregnancy. 3rd ed. New York. Wiley Liss Inc., 1998: 285–313Google Scholar
  67. 67.
    Stile I, Fort M, Warzburger R, et al. The pharmacokinetics of naloxone in the premature newborn. Dev Pharmacol Ther 1987; 10: 454–9PubMedGoogle Scholar
  68. 68.
    Nicolle E, Devillier P, Delanoy B, et al. Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate. Eur J Clin Pharmacol 1999; 49: 485–9CrossRefGoogle Scholar
  69. 69.
    Moya F, Kvisselgaard N. The placental transmission of succinylcholine. Anesthesiology 1961; 22: 1–6PubMedCrossRefGoogle Scholar
  70. 70.
    Baraka A, Haroun S, Bassili M, et al. Response of the newborn to succinylcholine injection in homozygotic atypical mothers. Anesthesiology 1975; 43: 115–6PubMedCrossRefGoogle Scholar
  71. 71.
    Owens W, Zeitlin G. Hypoventilation in a newborn following administration of succinylcholine to the mother: a case report. Anesth Analg 1975; 54: 38–40PubMedCrossRefGoogle Scholar
  72. 72.
    Dailey P, Fisher D, Shnider S, et al. Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during cesarean section. Anesthesiology 1984; 60: 569–74PubMedCrossRefGoogle Scholar
  73. 73.
    Abouleish E, Abboud T, Lechevalier T, et al. Rocuronium (Org 9426) for caesarean section. Br J Anaesth 1994; 72: 336–41CrossRefGoogle Scholar
  74. 74.
    Ramanathan S, Gandhi S, Arismendy J, et al. Oxygen transfer from mother to fetus during cesarean section under epidural anesthesia. Anesth Analg 1982; 61: 576–81PubMedGoogle Scholar
  75. 75.
    Turrens JF, Freeman BA, Crapo JD. Hyperoxia increases H2O2 release by lung mitochondria and microsomes. Arch Biochem Biophys 1982; 217: 411–21PubMedCrossRefGoogle Scholar
  76. 76.
    Khaw KS, Wang CC, Ngan Kee WD, et al. Effects of high inspired oxygen fraction during elective caesarean section under spinal anesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth 2002; 88: 18–23PubMedCrossRefGoogle Scholar
  77. 77.
    Dwyer R, Fee JP, Moore J. Uptake of halothane and isoflurane by mother and baby during caesarean section. Br J Anaesth 1995; 74: 379–83PubMedCrossRefGoogle Scholar
  78. 78.
    Crawford J. Awareness during operative obstetrics under general anesthesia. Br J Anaesth 1971; 43: 179–83PubMedCrossRefGoogle Scholar
  79. 79.
    Lawes E, Newman B, Campbell M, et al. Maternal inspired oxygen concentration and neonatal status for caesarean section under general anesthesia. Br J Anaesth 1988; 61: 250–4PubMedCrossRefGoogle Scholar
  80. 80.
    Mokriski B, Malinow A. Neonatal acid-base status following general anesthesia for emergency abdominal delivery with halothane or isoflurane. J Clin Anesth 1992; 4: 97–100PubMedCrossRefGoogle Scholar
  81. 81.
    Baker B, Hughes S, Shnider S, et al. Maternal anesthesia and the stressed fetus: effects of isoflurane on the asphyxiated fetal lamb. Anesthesiology 1990; 72: 65–70PubMedCrossRefGoogle Scholar
  82. 82.
    Warren T, Datta S, Ostheimer G, et al. Comparison of the maternal and neonatal effects of halothane, enflurane, and isoflurane for cesarean delivery. Anesth Analg 1983; 62: 516–20PubMedGoogle Scholar
  83. 83.
    Ghaly R, Flynn R, Moore J. Isoflurane as an alternative to halothane for caesarean section. Anaesthesia 1988 Jan; 43(1): 5–7PubMedCrossRefGoogle Scholar
  84. 84.
    Abboud T, D’Onofrio L, Reyes A, et al. Isoflurane or halothane for cesarean section: comparative maternal and neonatal effects. Acta Anaesthesiol Scand 1989; 33: 578–81PubMedCrossRefGoogle Scholar
  85. 85.
    Abboud TK, Zhu J, Richardson M, et al. Desflurane: a new volatile anesthetic for cesarean section: maternal and neonatal effects. Acta Anaesthesiol Scand 1995; 39: 723–6PubMedCrossRefGoogle Scholar
  86. 86.
    Abboud TK, Swart F, Zhu J, et al. Desflurane analgesia for vaginal delivery. Acta Anaesthesiol Scand 1995; 39: 259–61PubMedCrossRefGoogle Scholar
  87. 87.
    Eger E. New inhaled anesthetics. Anesthesiology 1994; 80: 906–22PubMedCrossRefGoogle Scholar
  88. 88.
    Gambling DR, Sharma SK, White PF, et al. Use of sevoflurane during elective cesarean birth: a comparison with isoflurane and spinal anesthesia. Anesth Analg 1995; 81(1): 90–5PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Jay E. Mattingly
    • 1
  • John D’Alessio
    • 2
  • Jaya Ramanathan
    • 1
    • 3
    Email author
  1. 1.Department of AnesthesiologyUniversity of Tennessee Health Sciences CenterMemphisUSA
  2. 2.Department of AnesthesiologyVanderbilt UniversityNashvilleUSA
  3. 3.Department of Obstetrics and GynecologyUniversity of Tennessee Health Sciences CenterMemphisUSA

Personalised recommendations