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Treating pain during pregnancy
Malaika Babb, PharmD, Gideon Koren, MD FRCPC FACMT and Adrienne Einarson, RN
My pregnant patients frequently ask about taking pain medications, sometimes for chronic conditions. What is known about the safety of using analgesics in therapeutic doses for acute or chronic pain during pregnancy?
Commonly prescribed pain medications appear to be relatively safe to use during pregnancy. None of the analgesics has been found to increase the risk of major malformations, although caution should be used when prescribing them in late pregnancy
Mes patientes enceintes me posent souvent des questions sur lusage des médicaments antidouleur, parfois pour des problèmes chroniques. Que sait-on des risques de lutilisation danalgésiques à doses thérapeutiques pour la douleur aiguë ou chronique durant la grossesse?
Les médicaments contre la douleur couramment prescrits semblent relativement sécuritaires durant la grossesse. Aucun analgésique ne sest encore avéré causer des risques accrus de malformations importantes, mais il vaut mieux être prudent lorsquon les prescrit en fin de grossesse.
Because of fear about use of drugs during pregnancy, some pregnant women would rather suffer than treat their pain. Consequently, it is possible that such women are at risk of undertreatment, or no treatment, for painful conditions. Chronic, severe pain that is ineffectively treated is associated with hypertension, anxiety, and depression—none of which is conducive to a healthy pregnancy.1,2
There are 2 main categories of commonly used analgesics: systemic nonopioid analgesics (eg, acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs [NSAIDs]) and opioid analgesics (eg, morphine, codeine, meperidine).
Acetaminophen, a nonsalicylate similar to aspirin in analgesic potency, has demonstrated efficacy and apparent safety at all stages of pregnancy in standard therapeutic doses. Its established safety profile for use has been demonstrated in a recent study of thousands of pregnant women, without increasing risks of congenital anomalies or other adverse pregnancy outcomes.3
Aspirin has potential risks, as it inhibits platelet function and can contribute to maternal and fetal bleeding.4 Although aspirin has not been associated with other congenital anomalies, it has been associated with increased risk of vascular disruption, in particular gastroschisis, although this remains unproven.5 Overall, large trials demonstrate low-dose aspirin’s relative safety and generally positive effects on reproductive outcomes.6
Nonsteroidal anti-inflammatory drugs
Nonsalicylate NSAIDs are known to relieve pain through peripheral inhibition of cyclooxygenase and hence inhibition of prostaglandin synthetase. They include drugs such as ibuprofen, naproxen, and ketorolac. To date, studies have failed to show consistent evidence of increased teratogenic effects in either humans or animals following therapeutic doses during the first trimester. However, even short-term use of NSAIDs in late pregnancy is associated with a substantial increase in the risk of premature ductal closure.7
These agents include morphine-like agonists (eg, morphine, hydromorphone, hydrocodone, codeine, and oxycodone), meperidine-like agonists, and synthetic opioid analogues (eg, tramadol). Reproductive studies describing the use of narcotic analgesics in human pregnancies are limited, and there are no prospective, comparative studies. However, these drugs have been used in therapeutic doses by pregnant women for many years and have not been linked to elevated risk of major or minor malformations. The Collaborative Perinatal Project identified 448 morphine exposures at various stages of pregnancy and found no evidence of increased teratogenic effects.8 The Michigan Medicaid study reported 332 newborns exposed to hydrocodone, 281 exposed to oxycodone, and 7640 exposed to codeine, all in the first trimester. The rate of major birth defects was 4.6% for the oxycodone-exposed group; 4.9% for the codeine-exposed group (consistent with the general population risk); and 7.2% for the hydrocodone group, which could have been influenced by confounding factors (ie, maternal disease severity and concurrent drug use).9 A case-control study of 141 infants with cardiac malformations did not report an association with the use of codeine in the first trimester of pregnancy.10 Neonatal withdrawal has been observed with use of codeine in late pregnancy, even with therapeutic doses in nonaddicted mothers.11,12
Several forms of fentanyl, including the patch, have been on the market for many years without reports of serious adverse effects, and it is considered effective for all types of chronic pain, including cancer and non-cancer pain.13 There is little information on its use in pregnancy, with only 2 case reports in the literature. In one, a high-dose fentanyl patch (ie, 125 µg/h) was used throughout pregnancy, and the newborn infant manifested mild withdrawal symptoms at 24 to 72 hours after birth.14 In the other, which was from the Motherisk team, a lower dose of the fentanyl patch was used with no apparent adverse effects.15
Medications used in therapeutic doses for acute and chronic pain appear to be relatively safe in pregnancy. To minimize fetal risk, initiate drug interventions at the lowest effective dose, especially in late pregnancy, and select analgesics only after careful review of a woman’s medical or medication history. Women should avoid using NSAIDs after 32 weeks’ gestation, owing to the possibility of antiplatelet or prolonged bleeding effects. Opioids should also be used with caution, especially in higher doses in late pregnancy when the infant should be observed carefully in the neonatal period for any signs of withdrawal (neonatal abstinence syndrome).
Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Drs Staroselsky, Klieger-Grossmann, and Garcia-Bournissen are members and Dr Koren is Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.
Can Fam Physician
Vol. 55, No. 12, December 2009, pp.1195 - 1198
Copyright ? 2009 by The College of Family Physicians of Canada
- Bruehl S, Chung OY, Jirjis JN, Biridepalli S. Prevalence of clinical hypertension in patients with chronic pain compared to non pain general medical patients. Clin J Pain 2005;21(2):147–53. [Medline]
- Whitten CE, Donovan M, Cristobal K. Treating chronic pain: new knowledge, more choices. Permanente J 2005;9(4):9–18. Available from: http://xnet.kp.org/permanentejournal/fall05/pain3.html. Accessed 2006 Jan 15.
- Rebordosa C, Kogevinas M, Bech BH, Sřrensen HT, Olsen J. Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. Int J Epidemiol 2009;38(3):706–14. Epub 2009 Mar 30.
[Abstract/Free Full Text]
- Werler MM, Mitchell AA, Moore CA, Honein MA. Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis? Am J Med Genet A 2009;149A(7):1399–406.
- Řstensen M, Förger F. Management of RA medications in pregnant patients. Nat Rev Rheumatol 2009;5(7):382–90. Epub 2009 Jun 9. [Medline]
- James AH, Brancazio LR, Price T. Aspirin and reproductive outcomes. Obstet Gynecol Surv 2008;63(1):49–57. [Medline]
- Koren G, Florescu A, Costei AM, Boskovic R, Moretti ME. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother 2006;40(5):824–9. Epub 2006 Apr 25. [CrossRef]
- Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group; 1977.
- Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. p. 319–20.
- Shaw GM, Malcoe LH, Swan SH, Cummins SK, Schulman J. Congenital cardiac anomalies relative to selected maternal exposures and conditions during early pregnancy. Eur J Epidemiol 1992;8(5):757–60. [Medline]
- Khan K, Chang J. Neonatal abstinence syndrome due to codeine. Arch Dis Child Fetal Neonatal Ed 1997;76(1):F59–60. [Abstract/Free Full Text]
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- Collado F, Torres LM. Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naive patients with severe chronic non-cancer pain. J Opioid Manag 2008;4(2):111–5. [Medline]
- Regan J, Chambers F, Gorman W, MacSullivan R. Neonatal abstinence syndrome due to prolonged administration of fentanyl in pregnancy. BJOG 2000;107(4):570–2. [Medline]
- Einarson A, Bozzo P, Taguchi N. Use of a fentanyl patch throughout pregnancy. J Obstet Gynaecol Can 2009;31(1):20. [Medline]