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J Pediatr Genet 2015; 04(02): 056-070
DOI: 10.1055/s-0035-1556740
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Prescription Opioids in Pregnancy and Birth Outcomes: A Review of the Literature

Mahsa M. Yazdy
1   Slone Epidemiology Center at Boston University, Boston, Massachusetts, United States
,
Rishi J. Desai
2   Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Susan B. Brogly
3   Department of Medicine and Surgery, Queen's University, Kingston, Ontario, Canada
› Author Affiliations
Further Information

Publication History

30 January 2015

05 February 2015

Publication Date:
31 July 2015 (online)

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Abstract

Prescription opioids are used prenatally for the management of pain, as well as for opiate dependency. Opioids are known to cross the placenta and despite the evidence of possible adverse effects on fetal development, studies have consistently shown prescription opioids are among the most commonly prescribed medications and the prevalence of use is increasing among pregnant women. This article summarizes the available literature documenting potential harms associated with prescription opioid use during pregnancy, including poor fetal growth, preterm birth, birth defects, and neonatal abstinence syndrome.

Keywords

opioids - pregnancy - fetal growth - birth weight - birth defects - neonatal abstinence syndrome
 

  • References

  • 1 Warner EA. Opioids for the treatment of chronic noncancer pain. Am J Med 2012; 125 (12) 1155-1161
    CrossrefPubMedGoogle Scholar
  • 2 Vanderah TW. Delta and kappa opioid receptors as suitable drug targets for pain. Clin J Pain 2010; 26 (Suppl. 10) S10-S15
    CrossrefPubMedGoogle Scholar
  • 3 U. S. Department of Justice, Drug Enforcement Administration. Drugs of abuse 2011 edition. Available at: http://www.dea.gov/docs/drugs_of_abuse_2011.pdf . Accessed September 15, 2014
    PubMedGoogle Scholar
  • 4 Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med 2003; 349 (20) 1943-1953
    CrossrefPubMedGoogle Scholar
  • 5 Chou R, Fanciullo GJ, Fine PG , et al; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009; 10 (2) 113-130
    CrossrefPubMedGoogle Scholar
  • 6 Sullivan MD, Edlund MJ, Fan MY, Devries A, Brennan Braden J, Martin BC. Trends in use of opioids for non-cancer pain conditions 2000-2005 in commercial and Medicaid insurance plans: the TROUP study. Pain 2008; 138 (2) 440-449
    CrossrefPubMedGoogle Scholar
  • 7 Von Korff M, Saunders K, Thomas Ray G , et al. De facto long-term opioid therapy for noncancer pain. Clin J Pain 2008; 24 (6) 521-527
    CrossrefPubMedGoogle Scholar
  • 8 Kenan K, Mack K, Paulozzi L. Trends in prescriptions for oxycodone and other commonly used opioids in the United States, 2000-2010. Open Med 2012; 6 (2) e41-e47
    PubMedGoogle Scholar
  • 9 Trescot AM, Glaser SE, Hansen H, Benyamin R, Patel S, Manchikanti L. Effectiveness of opioids in the treatment of chronic non-cancer pain. Pain Physician 2008; 11 (2, Suppl): S181-S200
    PubMedGoogle Scholar
  • 10 Noble M, Tregear SJ, Treadwell JR, Schoelles K. Long-term opioid therapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety. J Pain Symptom Manage 2008; 35 (2) 214-228
    CrossrefPubMedGoogle Scholar
  • 11 Martell BA, O'Connor PG, Kerns RD , et al. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction. Ann Intern Med 2007; 146 (2) 116-127
    CrossrefPubMedGoogle Scholar
  • 12 Chou R, Deyo R, Devine B , et al. The effectiveness and risks of long-term opioid treatment of chronic pain. In: Agency for Healthcare Research and Quality, ed. Evidence Report/Technology Assessment No. 218 (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290–2012–00014-I.). AHRQ Publication No. 14-E005-EF. Rockville, MD: Agency for Healthcare Research and Quality; ; September 2014
    Google Scholar
  • 13 Center for Substance Abuse Treatment. Medication-assisted treatment for opioid addiction in opioid treatment programs. Treatment Improvement Protocol (TIP) Series 43. DHHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration (US); 2005
    Google Scholar
  • 14 Riksheim M, Gossop M, Clausen T. From methadone to buprenorphine: changes during a 10 year period within a national opioid maintenance treatment programme. J Subst Abuse Treat 2014; 46 (3) 291-294
    CrossrefPubMedGoogle Scholar
  • 15 Stein BD, Gordon AJ, Sorbero M, Dick AW, Schuster J, Farmer C. The impact of buprenorphine on treatment of opioid dependence in a Medicaid population: recent service utilization trends in the use of buprenorphine and methadone. Drug Alcohol Depend 2012; 123 (1-3) 72-78
    CrossrefPubMedGoogle Scholar
  • 16 Volkow ND, Frieden TR, Hyde PS, Cha SS. Medication-assisted therapies—tackling the opioid-overdose epidemic. N Engl J Med 2014; 370 (22) 2063-2066
    CrossrefPubMedGoogle Scholar
  • 17 Wang SM, Dezinno P, Maranets I, Berman MR, Caldwell-Andrews AA, Kain ZN. Low back pain during pregnancy: prevalence, risk factors, and outcomes. Obstet Gynecol 2004; 104 (1) 65-70
    CrossrefPubMedGoogle Scholar
  • 18 Mogren IM, Pohjanen AI. Low back pain and pelvic pain during pregnancy: prevalence and risk factors. Spine 2005; 30 (8) 983-991
    CrossrefPubMedGoogle Scholar
  • 19 Bateman BT, Hernandez-Diaz S, Rathmell JP , et al. Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology 2014; 120 (5) 1216-1224
    CrossrefPubMedGoogle Scholar
  • 20 Babb M, Koren G, Einarson A. Treating pain during pregnancy. Can Fam Physician 2010; 56 (1) 25 , 27
    PubMedGoogle Scholar
  • 21 Mann R, Andrews E. Pharmacovigilance. West Sussex, England: John Wiley & Sons; 2007
    Google Scholar
  • 22 Mitchell AA. Studies of drug-induced birth defects. In: Strom B, Kimmel S, Hennessy S, , eds. Pharmacoepidemiology. 5th ed. West Sussex, United Kingdom: Wiley-Blackwell; 2012: 487-504
    CrossrefGoogle Scholar
  • 23 Stanhope TJ, Gill LA, Rose C. Chronic opioid use during pregnancy: maternal and fetal implications. Clin Perinatol 2013; 40 (3) 337-350
    CrossrefPubMedGoogle Scholar
  • 24 Food and Drug Administration, HHS. Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Final rule. Fed Regist 2014; 79 (233) 72063-72103
    PubMedGoogle Scholar
  • 25 Broussard CS, Rasmussen SA, Reefhuis J , et al; National Birth Defects Prevention Study. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol 2011; 204 (4) 314.e1-314.e11
    Google Scholar
  • 26 Bracken MB, Holford TR. Exposure to prescribed drugs in pregnancy and association with congenital malformations. Obstet Gynecol 1981; 58 (3) 336-344
    PubMedGoogle Scholar
  • 27 Rothman KJ, Fyler DC, Goldblatt A, Kreidberg MB. Exogenous hormones and other drug exposures of children with congenital heart disease. Am J Epidemiol 1979; 109 (4) 433-439
    PubMedGoogle Scholar
  • 28 Zierler S, Rothman KJ. Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy. N Engl J Med 1985; 313 (6) 347-352
    CrossrefPubMedGoogle Scholar
  • 29 Yazdy MM, Mitchell AA, Tinker SC, Parker SE, Werler MM. Periconceptional use of opioids and the risk of neural tube defects. Obstet Gynecol 2013; 122 (4) 838-844
    Google Scholar
  • 30 Engeland A, Bramness JG, Daltveit AK, Rønning M, Skurtveit S, Furu K. Prescription drug use among fathers and mothers before and during pregnancy. A population-based cohort study of 106,000 pregnancies in Norway 2004-2006. Br J Clin Pharmacol 2008; 65 (5) 653-660
    CrossrefPubMedGoogle Scholar
  • 31 Epstein RA, Bobo WV, Martin PR , et al. Increasing pregnancy-related use of prescribed opioid analgesics. Ann Epidemiol 2013; 23 (8) 498-503
    CrossrefPubMedGoogle Scholar
  • 32 Desai RJ, Hernandez-Diaz S, Bateman BT, Huybrechts KF. Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstet Gynecol 2014; 123 (5) 997-1002
    CrossrefPubMedGoogle Scholar
  • 33 Kellogg A, Rose CH, Harms RH, Watson WJ. Current trends in narcotic use in pregnancy and neonatal outcomes. Am J Obstet Gynecol 2011; 204 (3) 259.e1-259.e4
    CrossrefPubMedGoogle Scholar
  • 34 Martin CE, Longinaker N, Terplan M. Recent trends in treatment admissions for prescription opioid abuse during pregnancy. J Subst Abuse Treat 2015; 48 (1) 37-42
    CrossrefPubMedGoogle Scholar
  • 35 Melve KK, Gjessing HK, Skjaerven R, Oyen N. Infants' length at birth: an independent effect on perinatal mortality. Acta Obstet Gynecol Scand 2000; 79 (6) 459-464
    CrossrefPubMedGoogle Scholar
  • 36 Morris SS, Victora CG, Barros FC , et al. Length and ponderal index at birth: associations with mortality, hospitalizations, development and post-natal growth in Brazilian infants. Int J Epidemiol 1998; 27 (2) 242-247
    CrossrefPubMedGoogle Scholar
  • 37 Kajantie E, Osmond C, Barker DJ, Forsén T, Phillips DI, Eriksson JG. Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000 person-years. Int J Epidemiol 2005; 34 (3) 655-663
    PubMedGoogle Scholar
  • 38 Silva IdosS, De Stavola B, McCormack V ; Collaborative Group on Pre-Natal Risk Factors and Subsequent Risk of Breast Cancer. Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies. PLoS Med 2008; 5 (9) e193
    CrossrefPubMedGoogle Scholar
  • 39 Risnes KR, Vatten LJ, Baker JL , et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis. Int J Epidemiol 2011; 40 (3) 647-661
    CrossrefPubMedGoogle Scholar
  • 40 Wilcox AJ. Fertility and Pregnancy: An Epidemiologic Perspective. New York, NY: Oxford University Press; 2010
    Google Scholar
  • 41 Kelly L, Dooley J, Cromarty H , et al. Narcotic-exposed neonates in a First Nations population in northwestern Ontario: incidence and implications. Can Fam Physician 2011; 57 (11) e441-e447
    PubMedGoogle Scholar
  • 42 Hadi I, da Silva O, Natale R, Boyd D, Morley-Forster PK. Opioids in the parturient with chronic nonmalignant pain: a retrospective review. J Opioid Manag 2006; 2 (1) 31-34
    PubMedGoogle Scholar
  • 43 Källén B, Borg N, Reis M. The use of central nervous system active drugs during pregnancy. Pharmaceuticals (Basel) 2013; 6 (10) 1221-1286
    CrossrefPubMedGoogle Scholar
  • 44 Nezvalová-Henriksen K, Spigset O, Nordeng H. Effects of codeine on pregnancy outcome: results from a large population-based cohort study. Eur J Clin Pharmacol 2011; 67 (12) 1253-1261
    CrossrefPubMedGoogle Scholar
  • 45 Smith MV, Costello D, Yonkers KA. Clinical correlates of prescription opioid analgesic use in pregnancy. Matern Child Health J 2015; 19 (3) 548-556
    CrossrefPubMedGoogle Scholar
  • 46 Analgesics and antipyretic drugs. In: Heinonen OP, Slone D, Shapiro S, , eds. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group Inc; 1977: 286-295
    Google Scholar
  • 47 Rosa F. Personal communication. In: Briggs GG, Freeman RK, Yaffe SJ, , eds. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Philadelphia, PA: Lippincott Williams & Wilkins; 2011: 691-692
    Google Scholar
  • 48 Källén B. Drugs during Pregnancy. New York, NY: Nova Biomedical Books; 2009
    Google Scholar
  • 49 Khoury MJ, James LM, Flanders WD, Erickson JD. Interpretation of recurring weak associations obtained from epidemiologic studies of suspected human teratogens. Teratology 1992; 46 (1) 69-77
    CrossrefPubMedGoogle Scholar
  • 50 Bracken MB. Drug use in pregnancy and congenital heart disease in offspring. N Engl J Med 1986; 314 (17) 1120
    PubMedGoogle Scholar
  • 51 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) 757-760
    CrossrefPubMedGoogle Scholar
  • 52 Shaw GM, Todoroff K, Velie EM, Lammer EJ. Maternal illness, including fever and medication use as risk factors for neural tube defects. Teratology 1998; 57 (1) 1-7
    CrossrefPubMedGoogle Scholar
  • 53 Saxén I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemiol 1975; 4 (1) 37-44
    CrossrefPubMedGoogle Scholar
  • 54 Werler MM, Yazdy MM, Kasser JR , et al. Medication use in pregnancy in relation to the risk of isolated clubfoot in offspring. Am J Epidemiol 2014; 180 (1) 86-93
    CrossrefPubMedGoogle Scholar
  • 55 Kandall SR. Substance and Shadow: Women and Addiction in the United States. Cambridge, MA: Harvard University Press; 1999
    Google Scholar
  • 56 Jonnes J. The rise of the modern addict. Am J Public Health 1995; 85 (8 Pt 1) 1157-1162
    CrossrefPubMedGoogle Scholar
  • 57 Substance Abuse and Mental Health Services Administration. Results from the 2005 National Survey on Drug Use and Health: National Findings. Rockville, MD: Office of Applied Studies; , NSDUH Series H-30, DHHS Publication No. SMA 06-4194; 2006
    Google Scholar
  • 58 Knoppert D. The worldwide opioid epidemic: implications for treatment and research in pregnancy and the newborn. Paediatr Drugs 2011; 13 (5) 277-279
    CrossrefPubMedGoogle Scholar
  • 59 Hudak ML, Tan RC ; Committee on Drugs; Committee on Fetus and Newborn; American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics 2012; 129 (2) e540-e560
    CrossrefPubMedGoogle Scholar
  • 60 Centers for Disease Control and Prevention (CDC). Vital signs: overdoses of prescription opioid pain relievers and other drugs among women—United States, 1999-2010. MMWR Morb Mortal Wkly Rep 2013; 62 (26) 537-542
    PubMedGoogle Scholar
  • 61 Kandall SR, Albin S, Gartner LM, Lee KS, Eidelman A, Lowinson J. The narcotic-dependent mother: fetal and neonatal consequences. Early Hum Dev 1977; 1 (2) 159-169
    CrossrefPubMedGoogle Scholar
  • 62 Kaltenbach K, Berghella V, Finnegan L. Opioid dependence during pregnancy. Effects and management. Obstet Gynecol Clin North Am 1998; 25 (1) 139-151
    CrossrefPubMedGoogle Scholar
  • 63 Johnson K, Greenough A, Gerada C. Maternal drug use and length of neonatal unit stay. Addiction 2003; 98 (6) 785-789
    CrossrefPubMedGoogle Scholar
  • 64 Walsh SL, Preston KL, Bigelow GE, Stitzer ML. Acute administration of buprenorphine in humans: partial agonist and blockade effects. J Pharmacol Exp Ther 1995; 274 (1) 361-372
    PubMedGoogle Scholar
  • 65 U.S. Government Publishing Office. The Drug Addiction Treatment Act of 2000. Public Law No. 106–310. Available at: http://www.gpo.gov/fdsys/pkg/PLAW-106publ310/pdf/PLAW-106publ310.pdf . Accessed September 15, 2014
    PubMedGoogle Scholar
  • 66 Rettig RA, Yarmolinsky A , eds. Federal Regulation of Methadone Treatment. Washington, DC: The National Academy Press; 1995
    Google Scholar
  • 67 Kahila H, Saisto T, Kivitie-Kallio S, Haukkamaa M, Halmesmäki E. A prospective study on buprenorphine use during pregnancy: effects on maternal and neonatal outcome. Acta Obstet Gynecol Scand 2007; 86 (2) 185-190
    CrossrefPubMedGoogle Scholar
  • 68 Lejeune C, Simmat-Durand L, Gourarier L, Aubisson S ; Groupe d'Etudes Grossesse et Addictions (GEGA). Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution. Drug Alcohol Depend 2006; 82 (3) 250-257
    CrossrefPubMedGoogle Scholar
  • 69 Cleary BJ, Donnelly JM, Strawbridge JD , et al. Methadone and perinatal outcomes: a retrospective cohort study. Am J Obstet Gynecol 2011; 204 (2) 139.e1-139.e9
    CrossrefPubMedGoogle Scholar
  • 70 Cleary BJ, Eogan M, O'Connell MP , et al. Methadone and perinatal outcomes: a prospective cohort study. Addiction 2012; 107 (8) 1482-1492
    Google Scholar
  • 71 Pritham UA, Paul JA, Hayes MJ. Opioid dependency in pregnancy and length of stay for neonatal abstinence syndrome. J Obstet Gynecol Neonatal Nurs 2012; 41 (2) 180-190
    Google Scholar
  • 72 Kaltenbach K, Finnegan LP. Perinatal and developmental outcome of infants exposed to methadone in-utero. Neurotoxicol Teratol 1987; 9 (4) 311-313
    CrossrefPubMedGoogle Scholar
  • 73 Wouldes TA, Woodward LJ. Maternal methadone dose during pregnancy and infant clinical outcome. Neurotoxicol Teratol 2010; 32 (3) 406-413
    Google Scholar
  • 74 Dryden C, Young D, Hepburn M, Mactier H. Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG 2009; 116 (5) 665-671
    CrossrefPubMedGoogle Scholar
  • 75 Sharpe C, Kuschel C. Outcomes of infants born to mothers receiving methadone for pain management in pregnancy. Arch Dis Child Fetal Neonatal Ed 2004; 89 (1) F33-F36
    CrossrefPubMedGoogle Scholar
  • 76 Metz V, Jagsch R, Ebner N , et al. Impact of treatment approach on maternal and neonatal outcome in pregnant opioid-maintained women. Hum Psychopharmacol 2011; 26 (6) 412-421
    PubMedGoogle Scholar
  • 77 Welle-Strand GK, Skurtveit S, Jones HE , et al. Neonatal outcomes following in utero exposure to methadone or buprenorphine: a National Cohort Study of opioid-agonist treatment of Pregnant Women in Norway from 1996 to 2009. Drug Alcohol Depend 2013; 127 (1-3) 200-206
    CrossrefPubMedGoogle Scholar
  • 78 Kakko J, Heilig M, Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug Alcohol Depend 2008; 96 (1-2) 69-78
    CrossrefPubMedGoogle Scholar
  • 79 Jones HE, Kaltenbach K, Heil SH , et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med 2010; 363 (24) 2320-2331
    CrossrefPubMedGoogle Scholar
  • 80 Brogly SB, Saia KA, Walley AY, Du HM, Sebastiani P. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis. Am J Epidemiol 2014; 180 (7) 673-686
    CrossrefPubMedGoogle Scholar
  • 81 Hayes MJ, Brown MS. Epidemic of prescription opiate abuse and neonatal abstinence. JAMA 2012; 307 (18) 1974-1975
    CrossrefPubMedGoogle Scholar
  • 82 Jansson LM, Velez M. Neonatal abstinence syndrome. Curr Opin Pediatr 2012; 24 (2) 252-258
    CrossrefPubMedGoogle Scholar
  • 83 Wachman EM, Newby PK, Vreeland J , et al. The relationship between maternal opioid agonists and psychiatric medications on length of hospitalization for neonatal abstinence syndrome. J Addict Med 2011; 5 (4) 293-299
    CrossrefPubMedGoogle Scholar
  • 84 Jones HE, Johnson RE, Jasinski DR , et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend 2005; 79 (1) 1-10
    CrossrefPubMedGoogle Scholar
  • 85 Lacroix I, Berrebi A, Garipuy D , et al. Buprenorphine versus methadone in pregnant opioid-dependent women: a prospective multicenter study. Eur J Clin Pharmacol 2011; 67 (10) 1053-1059
    CrossrefPubMedGoogle Scholar
  • 86 Bakstad B, Sarfi M, Welle-Strand GK, Ravndal E. Opioid maintenance treatment during pregnancy: occurrence and severity of neonatal abstinence syndrome. A national prospective study. Eur Addict Res 2009; 15 (3) 128-134
    CrossrefPubMedGoogle Scholar
  • 87 Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA 2012; 307 (18) 1934-1940
    CrossrefPubMedGoogle Scholar