Elsevier

Seminars in Perinatology

Volume 39, Issue 7, November 2015, Pages 561-565
Seminars in Perinatology

Opioids in pregnancy and neonatal abstinence syndrome

https://doi.org/10.1053/j.semperi.2015.08.013Get rights and content

Abstract

Opiate use in pregnancy has increased dramatically over the past decade and now represents a major public health problem. More women are using prescription opioids, illegal opioids, and opioid-substitution therapy. These drugs have been associated with numerous obstetrical complications including intrauterine growth restriction, placental abruption, preterm delivery, oligohydramnios, stillbirth, and maternal death. Neonatal complications are also significant, such as an increased risk of mortality as well as neonatal abstinence syndrome (NAS). NAS is a serious and highly variable condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the management of opiate dependence in pregnancy and care of the neonate with prenatal opiate exposure. Since genetic factors appear to be associated with the incidence and severity of NAS, opportunities for “personalized genomic medicine” and unique therapeutic interventions could be developed in the future.

Section snippets

Prevalence of opiate use in pregnancy

Opiate use in the United States has risen dramatically in recent years. In 2012, prescribers wrote 82.5 opioid prescriptions and 37.6 benzodiazepine prescriptions per 100 persons, with significant variation observed between states and regions.1 Women of reproductive age have been significantly impacted, with approximately 28% of privately-insured and 39% of Medicaid enrolled women aged 15–44 years filling a prescription for an opioid medication each year between the years 2008–2012.2 Maternal

Maternal agonist treatment for opiate-dependent pregnant women

Maternal opioid-substitution programs have been shown to improve pregnancy outcomes by reducing withdrawal episodes and high-risk drug-seeking behaviors as well as improving compliance with prenatal care. Most of these programs use methadone, which is a full mu-opioid agonist in use since the 1970s.4 The pharmacokinetics of methadone in pregnant women differs from the non-pregnant population and changes significantly throughout pregnancy. For example, the half-life of methadone falls from an

Neonatal abstinence syndrome

NAS is a complex and highly variable condition characterized by central nervous system hyperirritability, autonomic nervous system dysfunction, and gastrointestinal disturbances. Frequently observed features include excessive crying, irritability, poor sleep, increased muscle tone, tremors, excoriations of the skin from excessive movements, hyperthermia, loose stools, yawning, sweating, nasal stuffiness, and sneezing. In addition, seizures can occur in 2–11% of the infants with NAS.16, 17

Treatment

The initial approach to NAS treatment is non-pharmacologic therapy which involves creating a gentle, soothing environment with minimal environmental stimulation for the neonate. Frequent hypercaloric feeds are typically administered to minimize hunger and promote growth. Maternal involvement in the infant’s care is an important component of non-pharmacologic management.16, 24

Pharmacologic treatment is required in the majority of infants with NAS.17 Several treatment approaches are used and no

Long-term follow-up

Adverse neurodevelopmental outcomes have been described in infants/children exposed in utero to opioids. However, there is a paucity of data regarding long-term neurodevelopmental function, as most studies are small and are unable to differentiate the effects of in utero exposures, postnatal treatments, and environmental influences. In general, opioid exposed children more likely to have attention deficit disorders, disruptive behavior, and the need for comprehensive psychiatric referrals.28, 29

Predictive factors

Factors that influence the onset and severity of NAS remain incompletely understood. Potential variables include maternal opiate dose, the specific maintenance agent, concurrent use of other drugs (e.g., nicotine, benzodiazepines, and selective serotonin reuptake inhibitors—SSRIs), gestational age, birth weight, and pharmacogenomics. Outcomes typically evaluated include treatment for NAS, peak NAS score, total dose required for treatment, duration of treatment, and length of hospitalization.

Future directions

As the number of pregnancies affected by maternal opiate dependence continues to rise, work is urgently needed to fill the significant knowledge gaps regarding optimal prenatal and postnatal care of opiate-dependent mothers and neonates. Specific areas of focus should include:

  • (1)

    Reducing opiate exposure in young women of child-bearing age.

  • (2)

    Improving maternal treatment programs to reduce the incidence and severity of NAS.

  • (3)

    Better identifying and treating high-risk neonates through personalized genomic

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