Approximately 4.4% of women of childbearing years use illicit drugs or abuse prescription medications, including marijuana, cocaine, hallucinogens, heroin, sedatives, painkillers, and stimulants.¹ Infants born to mothers who habitually use opioids (heroin, methadone, morphine, buprenorphine, meperidine, or codeine) can have physical manifestations of opiate withdrawal, termed neonatal abstinence syndrome (NAS). In recent years, the number of infants diagnosed with NAS nationally has increased significantly,² likely in part due to more liberal use of prescription opiates during pregnancy.³ Although NAS refers specifically to opiate withdrawal, similar symptoms can occur in infants with intrauterine exposure to other drugs.

PATHOPHYSIOLOGY

Placental passage to the fetus will vary depending on pharmacokinetic properties of each drug. Highly lipophilic drugs with a relatively low molecular weight are more likely to equilibrate rapidly between maternal and fetal circulation. They may then accumulate in the fetus due to renal and metabolic immaturity. Manifestations of withdrawal after delivery of the infant depend on various factors, including specific drug properties, dose and frequency of exposure, infant metabolism, and the interval between last exposure to the drug and delivery. Withdrawal is generally a function of the drug’s half-life; with a longer half-life being associated with later onset of withdrawal and potentially decreased likelihood of NAS.

Maternal polysubstance use can potentiate or delay neonatal withdrawal symptoms. Infants of mothers who use narcotics and also smoke cigarettes may have heightened symptoms of NAS. Opiate use combined with sedative use during pregnancy may mask infant withdrawal symptoms for up to 2 weeks. Another factor known to cause delayed or protracted infant withdrawal is prolonged maternal use of high-dose methadone; complete withdrawal for these infants may take up to 4 months.⁴

Nearly all infants with chronic intrauterine exposure to opioids have some symptoms of NAS, and 25% require pharmacologic intervention.⁴ Infants born to mothers who use opiates usually present with symptoms within the first 72 to 96 hours of life. Withdrawal symptoms can be classified into three areas: central nervous system (CNS), autonomic nervous system, and gastrointestinal (GI) symptoms (see Table 131-1). Skin excoriation on the buttocks (due to excessive stooling) and the elbows and knees (due to friction burns secondary to tremors) is also well described. Additionally, infants with intrauterine opiate exposure are at increased risk of reduced fetal growth parameters, prematurity, and low birth weight.

Mild NAS symptoms may persist until age 4 months, even after successful medical management.⁵ Sleep may continue to be disorganized, and hyperreflexia and hypertonia may continue, but tremor and jitteriness usually resolve earlier. GI disturbances such as loose stools, emesis, and colic also tend to resolve later in the withdrawal process. An increased incidence of sudden infant death syndrome has been reported in this population. In addition, there is a higher incidence of child abuse, possibly associated with maternal isolation, poor parenting preparation and skills, increased infant irritability, and the stresses of ongoing maternal drug use or recovery.⁵

Long-term effects of opioid withdrawal are not clearly defined. In many infants the withdrawal hypertonia changes to post-withdrawal hypotonia. Eye abnormalities such as esotropia, opsoclonus, and nystagmus have been described. There is some evidence that intrauterine opiate exposure leads to problems such as attention-deficit hyperactivity disorder, cognitive deficits, and poorly developed organizational and adaptive skills, although these behaviors may be related to home and social environment rather than drug exposure.⁶

Careful consideration needs to be given to the differential diagnosis of NAS. An infant should not be treated for narcotic withdrawal if exposure cannot be confirmed. The differential diagnosis of NAS in an infant less than 2 weeks of age can include electrolyte abnormalities (e.g. hypoglycemia, hypomagnesemia, hypercalcemia, hypocalcemia) or neonatal hyperthyroidism. Infantile colic, formula intolerance, or severe gastroesophageal reflux may present with symptoms similar to NAS. Infants exposed in utero to large amounts of caffeine, antidepressants,⁷ nicotine, or alcohol may also present with NAS-like symptoms.

In the case of known intrauterine exposure to opiates or other illicit drugs, urine and meconium or umbilical cord toxicology screens are indicated. This testing may detect polysubstance use that might not have been revealed in the maternal history. If an infant presents with symptoms consistent with NAS and there is no reported history of maternal drug use, maternal drug use is still a possibility. If the mother abstained from drug use just before delivery, both she and her infant may have negative urine toxicology screens in the peripartum period. In the presence of a negative urine screen, a meconium or cord screen may be helpful in defining in utero exposure to narcotics and risk for NAS. If maternal drug abuse is verified, it is important to test the mother for sexually transmitted diseases, such as human immunodeficiency virus, hepatitis B, hepatitis C, syphilis, gonorrhea, and chlamydia, because of their higher risk for infection.