Opioid use in the United States has reached epidemic proportions; the number of opioid-involved overdose deaths was five times higher in 2016 than it was in 1999.1 The opioid crisis involves heroin and other illegal drugs in addition to prescription drugs. Three significant changes have occurred as deaths from prescription opioids rose between 1999 and 2016:
- In 2010, the number of heroin overdose deaths significantly increased.
- In 2013, the number of deaths caused by synthetic opioid overdoses increased sharply.2
- In 2015, the CDC stated that over the previous decade, heroin use more than doubled in adults ages 18 to 25 years.3
Opioid use disorder is defined by a pattern of opioid use that results in clinically significant patient distress or impairment. Within a 12-month period, patients must have at least two of 11 diagnostic criteria, which include cravings, withdrawal, tolerance, reduction in previously enjoyed activities, and continued opioid use in dangerous situations.4 One population in particular that has been affected by the increase in opioid use and misuse is women of childbearing age; each year, from 2008 to 2012, 28% of women of reproductive age with private insurance and 39% of women of reproductive age enrolled in Medicaid filled opioid prescriptions.5
Opioid use in pregnancy can increase the risk for fetal neural tube defects, congenital heart defects, and gastroschisis.5 Despite the increased risks of pregnancy and birth complications, antepartum maternal opioid use increased from 1.19 to 5.63 per 1,000 hospital births from 2000 to 2009.6 The escalation has contributed to an increased incidence of neonatal abstinence syndrome (NAS), a postnatal drug withdrawal disorder affecting newborns.7 Rates of NAS increased from 3.4 per 1,000 hospital births in 2009 to 5.8 per 1,000 in 2012.7 NAS is associated with prolonged hospital stays, increased medical expenses, and a large number of medical complications, including low birth weight, significant respiratory issues such as meconium aspiration and respiratory distress syndrome, feeding difficulty, sepsis, and seizures.7 The mean hospital stay and hospital bill for an uncomplicated term baby in 2012 was 2.1 days and $3,500, compared with 23 days and $93,400 for a baby with NAS.7 With the weighty consequences faced by mothers, fetuses, and society as a whole, medical providers need to be prepared to screen patients for opioid use disorder, intervene appropriately, and refer patients for treatment. Since the Comprehensive Addiction and Recovery Act was signed into law in 2016, PAs and NPs interested in offering medication-assisted treatment (MAT) with buprenorphine can obtain training that lets them prescribe buprenorphine for up to 30 patients.8
Opioids bind to mu, delta, and kappa receptors, blocking the intensity of pain signals.9 Because their pain-blocking effects also can cause euphoria, opioids can be misused. Continued long-term use of opioids can lead to opioid use disorder. Commonly prescribed opioids include codeine, fentanyl, morphine, oxycodone, hydromorphone, and hydrocodone. Heroin is a short-acting illegal opioid that carries significant abuse potential.
Symptoms of opioid use disorder include physical dependence, development of tolerance, habitual drug-seeking behaviors, and drug cravings. Symptoms of opioid withdrawal may include muscle pain, restlessness, anxiety, diaphoresis, tearing, rhinorrhea, dilated pupils, nausea, diarrhea, tremors, and cold intolerance.10 Opioid misuse and dependency during pregnancy have been linked to significant maternal and fetal morbidity and mortality.11 Obstetric complications include miscarriage, abruptio placentae, fetal death, fetal growth restriction, preterm birth, and placental insufficiency.11 In addition to obstetric-specific complications, women with opioid use disorder are more likely to suffer from polysubstance abuse and engage in high-risk behaviors, resulting in violence, incarceration, and exposure to sexually transmitted infections.10
In 2017, the American College of Obstetrics and Gynecology (ACOG) and the American Society of Addiction Medicine (ASAM) collaboratively developed recommendations to guide clinicians caring for pregnant patients with opioid use disorder. The cornerstone of these recommendations was the SBIRT strategy: Universal Screening, Brief Intervention, and Refer for Treatment.10 Screening for substance abuse should be standard practice at every woman's first prenatal visit, regardless of patient ethnicity or socioeconomic status.12 Clinicians should use a validated screening tool (Table 1).13 However, these screening tools cannot identify patients with opioid use disorder if patients do not seek prenatal care or answer questions honestly.
If screening indicates that a patient may be at risk for opioid use disorder, the next step is the brief intervention. This involves engaging the patient in a brief, nonjudgmental conversation, providing feedback and advice, and referring the patient to appropriate treatment services.10 Mandatory reporting varies widely depending on state; clinicians must accurately understand these laws before initiating patient care.
According to ACOG, patients with opioid use disorder should be referred to a substance use disorder treatment program and receive MAT, which combines behavioral therapy with opioid agonist pharmacotherapy.10
The two main treatments for pregnant women with opioid use disorder are opioid agonist MAT with medications such as methadone or buprenorphine, and opioid detoxification. Although evidence is lacking that opioid detoxification is associated with fetal loss, it is not recommended for pregnant women because of the high rates of maternal relapse and potential fetal risks associated with cycles of intoxication and withdrawal.10,13-15 Patients who attempt opioid detoxification during pregnancy should be under the supervision of a clinician experienced in peripartum addiction and should also have psychosocial interventions.13 Pregnant patients insistent on withdrawing from opioids should demonstrate commitment to treatment and have plenty of support, as it will be an extended process with many challenges.14
The safest time for initiating opioid detoxification in pregnancy is the second trimester, and the best results are seen in programs that gradually taper methadone based on maternal symptoms.14,15 Maternal demographics and drug history do not correlate with successful opioid detoxification; clinicians willing to supervise opioid detoxification during pregnancy can improve outcomes by providing sensitive and supportive care to all patients, regardless of maternal demographics or background.14
The gold standard for MAT in pregnancy, methadone has been studied more extensively than buprenorphine, a promising newer option. In 1974, a program was developed for pregnant women, their partners, and their newborns focused on controlling withdrawal symptoms, reducing cravings, and preventing illicit opioid use by providing mothers with daily methadone and powerful psychosocial support.13,16 Patients in the program had increased adherence to obstetric care, which in turn reduced rates of complications.16 This type of methadone program is still in existence today. Methadone treatment must be initiated while the woman is an inpatient or in a licensed outpatient methadone program, and methadone must be dispensed daily, even after the maintenance dosage has been reached.10 Physiologic changes during pregnancy include increased intravascular volume, renal profusion, and glomerular filtration rate that increase renal elimination of methadone, so increasing the dosage typically is necessary.13 Only 8% of women remain on the same daily dosage of methadone throughout pregnancy; 86% of women require dosage increases due to withdrawal symptoms.17 Although increasing methadone dosages may raise concern for increased severity and/or incidence of NAS, research has been unable to link the two.13,17 Dose reduction after pregnancy should be based on signs and symptoms of overmedication, which include sedation, miosis, itching, hypotension, and respiratory depression.17,18 However, methadone dosages often are not reduced for the first 6 weeks postpartum.17
Research comparing methadone and buprenorphine use during pregnancy revealed that buprenorphine is associated with fewer preterm births, higher birth weights, larger head circumferences at birth, lower risks of NAS, and shorter hospital stays for babies born with NAS.19,20 Unlike methadone, buprenorphine can be prescribed and initiated in an office-based setting by trained providers, including PAs and NPs, and may be dispensed either weekly or biweekly.13 Outpatient treatment reduces the social stigma and shame associated with opioid use disorder and is more convenient for patients, reducing barriers to treatment and increasing adherence.21
Buprenorphine is a partial mu receptor agonist, meaning that when bound to opioid receptors, it does not undergo as much conformational change as full agonists such as heroine and methadone.13 Buprenorphine drug activity plateaus at higher doses, reducing the risk of overdose compared with full receptor agonists. The potential downside is that at dosages greater than 32 mg, the drug has a “ceiling effect” in which its effect does not significantly increase despite dosage increases.22 Dosing depends on withdrawal symptoms; some patients require as little as 4 mg per day and others the full 32 mg.22
Buprenorphine treatment is not recommended for all pregnant patients with opioid use disorder. Methadone treatment programs provide more structure, support, and supervision: successful buprenorphine treatment requires that the patient express a preference for buprenorphine over methadone, the patient provide informed consent for treatment, and that the patient is capable of safely self-administering the medication and adhering to a schedule.13,23
Buprenorphine can be manufactured in combination with naloxone for MAT; the combination prevents drug diversion because it precipitates severe withdrawal symptoms if injected.13 When comparing pregnant women treated with buprenorphine-naloxone with those treated with either buprenorphine alone or methadone, no significant differences were found in maternal outcomes.24-26 Although multiple studies have found no significant differences in neonatal outcomes among the different MAT groups, more research is needed in this area. Based on available research, buprenorphine-naloxone does not appear to pose a greater risk to the fetus or neonate.24,25 However, some studies have demonstrated that neonates exposed to buprenorphine-naloxone in utero had significantly lower APGAR scores at 5 minutes compared with neonates exposed to buprenorphine alone.26 Given the uncertainty about naloxone's effects on the mother, fetus, and neonate, buprenorphine alone is preferred over buprenorphine-naloxone for pregnant patients with opioid use disorder.10,13
The US Substance Abuse and Mental Health Services Administration has a list of opioid disorder treatment programs by state at http://dpt2.samhsa.gov/treatment/directory.aspx.
OTHER ISSUES TO CONSIDER
When caring for a pregnant woman with opioid use disorder, clinicians must take several additional factors into account beyond the patient's addiction.
A common misconception is that mothers receiving medication to treat opioid use disorder are unable to breastfeed; however, breastfeeding is not only safe but recommended. Studies have shown that breastfed infants whose mothers are on MAT have reduced severity of NAS, require less pharmacotherapy to treat their NAS, and spend fewer days in the hospital after birth.27 Maternal transfer of methadone and buprenorphine in breast milk is minimal and considered safe.27 Contraindications to breastfeeding include continued illicit drug use, HIV, and active hepatitis C with bleeding nipples.10
Another important factor to consider when providing treatment with MAT is pain control during and after labor. Women receiving MAT often require higher doses of analgesia to control their pain. Patients may choose to consult an anesthesiologist before giving birth to create an individualized pain management plan for labor, delivery, and the postpartum period.10
Prenatal care presents an opportunity to address smoking during pregnancy. Between 85% and 90% of pregnant women in MAT programs smoke tobacco products despite the increased risk of placental abruption, intrauterine growth restriction, preterm delivery, low birth weight, and stillbirth.28 This rate is significantly higher than the 16% smoking rate in the general population of pregnant women.28 Providers should stress the importance of smoking cessation and provide resources to help patients stop smoking.
Mental and sexual health
Because pregnant patients with opioid use disorder are more likely to suffer from concomitant psychiatric illness, mental health screening and referrals are often necessary for this population.29 The increased likelihood of pregnant women with opioid use disorder engaging in high-risk behaviors means that clinicians may need to increase the frequency at which these patients are screened for sexually transmitted infections.10,30 A multidisciplinary approach is optimal, involving an obstetric provider, an addiction medicine specialist, and other specialists as necessary. This comprehensive approach to care should continue through the postpartum period to ensure that the mother and baby continue to receive adequate treatment and support after delivery.
With rates for opioid abuse and misuse continuing to climb, especially in women of childbearing age, all women should be screened for opioid use disorder at the first prenatal appointment. Opioid use disorder in pregnancy is a complicated issue that requires communication between all clinicians involved in the patient's care. Clinicians who are supportive, nonjudgmental, and able to effectively communicate with the patient and her treatment team are more likely to see positive results.
Treatment options for pregnant patients with opioid use disorder include MAT with buprenorphine, methadone, or a combination of buprenorphine and naloxone, and opioid detoxification. If successful, detoxification greatly reduces the risks of NAS and results in an opioid-free mother at the time of delivery; however, it is associated with high rates of relapse, which poses significant risks to both mother and fetus. Treatment with either buprenorphine or methadone increases the risk for NAS but is the recommended treatment option because it has lower rates of maternal relapse. Buprenorphine-naloxone use is not recommended due to limited data on its effects.
Regardless of the treatment option selected, patients need a comprehensive treatment plan that includes prenatal care, addiction counseling, family therapy, and other appropriate psychosocial and medical support.13 Before prescribing an opioid medication, all clinicians must be certain that it is appropriately indicated. This involves obtaining a thorough patient history to assess for past or present substance abuse or abuse potential; reviewing the prescription drug monitoring program; and educating patients on the risks, benefits, and treatment goals.10 PAs and NPs now have the ability to play a critical role in the care of pregnant patients with opioid use disorder through early universal screening, appropriate intervention, referrals, and treatment.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders
. 5th ed. Arlington, VA; 2013.
5. Broussard CS, Rasmussen SA, Reefhuis J, et al Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol
6. Patrick SW, Schumacher RE, Benneyworth BD, et al Neonatal abstinence syndrome
and associated health care expenditures: United States, 2000-2009. JAMA
7. Patrick SW, Davis MM, Lehman CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome
: United States 2009 to 2012. J Perinatol
9. Zöllner C, Stein C. Opioids. Handb Exp Pharmacol
10. American College of Obstetricians and Gynecologists. Committee on Obstetric Practice. Committee Opinion No. 711: Opioid use and opioid use disorder
. Obstet Gynecol
11. Maeda A, Bateman BT, Clancy CR, et al Opioid abuse and dependence during pregnancy
: temporal trends and obstetrical outcomes. Anesthesiology
12. American College of Obstetricians and Gynecologists. Committee Opinion No. 633: Alcohol abuse and other substance use disorders: ethical issues in obstetric and gynecologic practice. Obstet Gynecol
13. Reddy UM, Davis JM, Ren Z, Greene MF. Opioid use in pregnancy
, neonatal abstinence syndrome
, and childhood outcomes. Obstet Gynecol Surv
14. Stewart RD, Nelson DB, Adhikari EH, et al The obstetrical and neonatal impact of maternal opioid detoxification in pregnancy
. Am J Obstet Gynecol
15. Luty J, Nikolaou V, Bearn J. Is opiate detoxification unsafe in pregnancy
. J Subst Abuse Treat
16. Harper RG, Solish GI, Purow HM, et al The effect of a methadone
treatment program upon pregnant heroin addicts and their newborn infants. Pediatrics
17. Albright B, de la Torre L, Skipper B, et al Changes in methadone
maintenance therapy during and after pregnancy
. J Subst Abuse Treat
18. Leavitt SB. Methadone
dosing and safety in the treatment of opioid addiction. Addict Treat Forum
19. Jones HE, Finnegan LP, Kaltenbach K. Methadone
for the management of opioid dependence in pregnancy
20. Zedler BK, Mann AL, Kim MM, et al Buprenorphine
compared with methadone
to treat pregnant women with opioid use disorder
: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction
21. Alto WA, O'Connor AB. Management of women treated with buprenorphine
. Am J Obstet Gynecol
22. Substance Abuse and Mental Health Services Administration. Center for Substance Abuse Treatment. Clinical guidelines for the use of buprenorphine
in the treatment of opioid addiction, 2004. Report No.: (SMA) 04-3939.
23. Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National practice guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med
24. Debelak K, Morrone WR, O'Grady KE, Jones HE. Buprenorphine
+ naloxone in the treatment of opioid dependence during pregnancy
—initial patient care and outcome data. Am J Addict
25. Dooley J, Gerber-Finn L, Antone I, et al Buprenorphine
-naloxone use in pregnancy
for treatment of opioid dependence: retrospective cohort study of 30 patients. Can Fam Physician
26. Lund IO, Fischer G, Welle-Strand GK, et al A comparison of buprenorphine
+ naloxone to buprenorphine
in the treatment of opioid dependence during pregnancy
: maternal and neonatal outcomes. Subst Abuse
27. Bagley SM, Wachman EM, Holland E, Brogly SB. Review of the assessment and management of neonatal abstinence syndrome
. Addict Sci Clin Pract
28. Akerman SC, Brunette MF, Green AI, et al Treating tobacco use disorder in pregnant women in medication-assisted treatment for an opioid use disorder
: a systematic review. J Subst Abuse Treat
29. Benningfield MM, Arria AM, Kaltenbach K, et al Co-occurring psychiatric symptoms are associated with increased psychological, social, and medical impairment in opioid dependent pregnant women. Am J Addict
30. Krans EE, Zickmund SL, Rustgi VK, et al Screening and evaluation of hepatitis C virus infection in pregnant women on opioid maintenance therapy: a retrospective cohort study. Subst Abuse
Keywords:Copyright © 2019 American Academy of Physician Assistants
opioid use disorder; pregnancy; fetal development; methadone; buprenorphine; neonatal abstinence syndrome