• Symptoms of increased autonomic reactivity in neonate exposed in utero to opiates

ICD-9 codes

• 779.5 drug withdrawal syndrome in newborn
• 760.72 narcotics affecting fetus or newborn via placenta or breast milk
• 763.5 maternal anesthesia and analgesia affecting fetus or newborn

Risk factors

• Higher maternal methadone dose may correlate with increased risk.
• Infants of mothers using methadone for pain control (rather than addiction) may have lower risk.
• Preterm infants appear to be at lower risk.

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History in the infant

• Fever, inability to sleep, and poor feeding (Infants withdrawing from methadone, however, may display hyperphagia.)
• Vomiting/diarrhea resulting in weight loss and dehydration
• Symptom onset usually within 48-72 hours of birth but depends on half-life of drug (e.g., methadone withdrawal may present up to four weeks post partum)

Physical exam

• Irritability, hypertonia, tremors, or seizures
• Yawning, sneezing, mottling, fever, nasal flaring


• Ascertain extent of maternal drug use during pregnancy.
• Toxicology testing 
    — Urine: accuracy depends on timing of urine sample collection in relation to maternal drug use.
    — Meconium: may be more sensitive and easier to obtain than a complete interview with the mother or maternal hair sample.
    — Umbilical cord tissue sampling: as reliable as meconium analysis; may provide more rapid results
    — Blood: of little value due to rapid metabolism and low drug concentrations
    — Neonatal hair: difficult to obtain adequate sample; slow hair growth limits detection of recent exposure.
• Rule out (in the infant)
    — Withdrawal syndromes related to benzodiazepines, cocaine, alcohol, selective serotonin reuptake inhbitors, etc. 
    — Hypoglycemia, hypocalcemia, or hypomagnesemia 
    — Hyperthyroidism
    — Infection/sepsis
    — Central nervous system hemorrhage
    — Anoxia


• Severe withdrawal does not necessarily portend poor long-term outcome.
• Association between prenatal opiate exposure and neurodevelopmental outcomes inconsistent

Nonpharmacologic treatment

• Supportive care
    — Adequate nutrition
    — IV fluid and electrolyte replacement as needed
    — Measures to minimize sensory stimulation (e.g., swaddling, temperature stability)
• Breast milk intake might be associated with reduced severity of withdrawal symptoms.
• Prone positioning of infant may reduce severity of syndrome but also associated with decreased caloric intake.
• Use of nonoscillating waterbeds associated with decreased need for medication, but mechanical rocking beds appear to worsen withdrawal symptoms.

Indications for pharmacologic therapy

• Seizures, poor feeding, severe vomiting/diarrhea, sleeplessness, fever
• High withdrawal severity score on scales developed to assess neurologic, GI, respiratory, and metabolic status
    — Treatment threshold determined by average severity score on three consecutive exams
    — Numerical thresholds for two most commonly used scoring systems, both employing 0- to 3-point scales to gauge individual signs of withdrawal (e.g., increased muscle tone, tremors, vomiting)
        • Modified Finnegan score >8
        • Lipsitz score >4
    — Movement quantified by motion detector (actigraph on infant leg) may predict need for pharmacologic intervention.


• Opioids (e.g., tincture of opium, morphine, or methadone) generally recommended as medications of choice, but
    — May result in increased duration of hospital stay
    — No studies have evaluated the rate at which withdrawal medication should be weaned, so rate is determined by clinical symptoms.
• Sedatives (e.g., phenobarbitone, diazepam) generally not preferred as initial treatment 
    — Compared with opioids, sedatives may be associated with longer duration of treatment and greater incidence of treatment failure, seizures, and nursery admission. 
    — Addition of phenobarbitone to opium may reduce withdrawal severity, length of hospital stay, and maximum daily opium dose.
• Naloxone (Narcan) and clonidine (Catapres) have limited data regarding efficacy and safety in infants.


• Avoid prenatal maternal opiate use, especially in third trimester.
• No particular agent has been shown to reduce incidence of dependence in neonate if opioid agonist therapy is required during pregnancy.


• Maternal medication and drug history
• Red flags in history and physical exam that may suggest diagnosis of fetal drug exposure include
    — Maternal history of severe mood swings, hypertensive episodes, cerebrovascular accident, or MI
    — Failure on the part of  mother to obtain appropriate prenatal care 
    — History of placental abruption, precipitous labor, unexplained fetal demise, or repeated spontaneous abortion
    — Intrauterine growth retardation/prematurity 
    — Neurobehavioral abnormalities
    — Urogenital anomalies 
    — Atypical vascular incidents, such as stroke, MI, or necrotizing enterocolitis

For complete references, see

Dr. Brier is an editor for DynaMed (, a database of comprehensive updated summaries covering more than 3,000 clinical topics. Dr. Bellet is pediatrics editor for DynaMed.