Neonatal Abstinence Syndrome: How Can Pharmacists Help?

Question

What role can pharmacists play in preventing and treating neonatal abstinence syndrome?

Response from Lindsay A Slowiczek, PharmD
Drug Information Research Fellow; Instructor, Pharmacy Practice, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska

As rates of opioid use continue to increase, the epidemic has extended to pregnant patients and become a growing public health concern. Analysis of a large Medicaid claims database found that between 2000 and 2007, 21.6% of over 1.1 million pregnant women received an opioid prescription, and more than 2% received greater than 30 days of treatment with opioids while pregnant.^[1] The proportion of women receiving opioids during pregnancy increased nationally from 18.5% in 2000 to 22.8% in 2007.^[2] It is expected that these numbers have increased sharply over the past decade. Additionally, the actual prevalence of prenatal opioid exposure remains unknown, as studies are unable to account for illicit drug use or pain medications taken without a prescription.

Increased opioid use during pregnancy has resulted in elevated fetal risk and a greater incidence of neonatal abstinence syndrome (NAS). The number of infants experiencing withdrawal symptoms (eg, jitteriness, tremors, diaphoresis, loose stools, poor feeding, weight loss, tachycardia, excoriations, excessive crying/irritability, and seizures) due to NAS increased nationally from 3.4 per 1000 hospital births in 2009 to 5.8 in 2012.^[3] Maternal polysubstance abuse with drugs such as antidepressants, benzodiazepines, gabapentin, and marijuana can compound NAS symptoms and may prolong inpatient treatment.^[4]

Reducing the Risk for and Severity of NAS

Screening women of childbearing age for opioid use or abuse to identify those who may require medication-assisted therapy is an important step that community and clinical pharmacists can take to help reduce the incidence or severity of NAS. According to an international survey, more than 80% of pregnancies are unintended in women who abuse opioids, a number that is two to three times the rate in the general population.^[5] A survey of Tennessee pharmacists identified important opportunities for increased engagement between patients and community pharmacists, particularly regarding conversations about pregnancy status, use of birth control, the risks of opioid use during pregnancy, and resources for obtaining long-acting, reversible contraception or referrals for drug abuse treatment, if needed.^[6] Frequent and continued communication between pharmacists who are dispensing opioids to women of childbearing age is essential to educating women on the dangers of NAS.

Maintenance therapy with either methadone or buprenorphine is recommended for pregnant patients with opioid use or abuse disorders. Buprenorphine may be associated with better outcomes for infants, such as greater gestational age, weight, and head circumference and shorter duration of NAS treatment. Despite this, buprenorphine interacts with CYP3A4 inhibitors and antiretroviral agents, lacks long-term infant and child safety outcomes, and may be associated with higher maternal relapse rates.^[7,8,9] Regardless of maintenance drug choice, patients who are tolerating therapy should be encouraged to continue their initial regimen to minimize risk for treatment lapse or failure.^[8]

Treating the Infant Born With NAS

Nonpharmacologic treatment strategies are essential to providing comprehensive perinatal therapy for newborns with NAS. Ensuring that newborns are kept in soothing environments that are free from excitatory noise or light, as well as implementing a rooming-in policy for the mother-infant pair, can help reduce symptom severity and opioid treatment requirements and can also decrease treatment duration.^[10] According to the Academy of Breastfeeding Medicine, the American Congress of Obstetricians and Gynecologists, and the American Academy of Pediatrics (AAP), mothers adherent to maintenance therapy with methadone or buprenorphine, regardless of dose, should be counseled on the importance of breastfeeding. Newborns with NAS who are breastfed experience greater bonding with the mother and are less likely to require pharmacologic treatment for NAS. Both agents have been shown to be safe for the infant; very small concentrations of either agent have been detected in breast milk. Contraindications to breastfeeding include HIV/AIDS infection, use of illicit or prescription drugs incompatible with breastfeeding, and risk for relapse. Mothers should also be encouraged to avoid abrupt discontinuation of breastfeeding, as this may be associated with rebound NAS symptoms.^[11] Pharmacists can play an important role in educating both mothers and healthcare providers about the importance of nonpharmacologic NAS treatment strategies, particularly regarding the benefits and safety of breastfeeding during maintenance therapy.

The AAP recommends pharmacologic treatment for NAS in neonates with moderate to severe withdrawal symptoms who have inadequate response to nonpharmacologic treatment. The most common first-line pharmacologic treatment options are oral morphine and methadone, though there is limited and conflicting evidence to recommend one agent over the other.^[12] Sublingual buprenorphine is also being investigated as a potential first-line agent and has been shown to be beneficial.^[13] For infants who have inadequate response to the maximum dose of initial treatment, phenobarbital or clonidine may augment therapy, though their long-term efficacy and safety data are limited. The lowest necessary dose and preservative- and alcohol-free formulations are recommended for all options. Regardless of agent, AAP stresses that length of NAS treatment should be minimized to facilitate development of mother-infant bond and to reduce the risk for adverse effects from antenatal opioid use.^[12] Studies have shown that standardization of symptom assessment and treatment or weaning protocols can decrease length of treatment and reduce newborns’ drug exposure, regardless of drug or protocol.^[14] Pharmacists advocating for development of standardized protocols can help improve neonatal outcomes and reduce potentially harmful exposure to pharmacologic agents.

As the healthcare profession continues to grapple with the consequences of an opioid epidemic, pharmacists can advocate for improved patient education to help reduce the incidence and severity of NAS, as well as for the implementation of evidence-based practices designed to improve NAS outcomes.

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