Definition of Neonatal Abstinence Syndrome (NAS) A condition that an infant experiences

when withdrawing from certain drugs that his/her mother took during pregnancy

Incidence

5-10% of deliveries nationwide are to women who have abused drugs during pregnancy (excluding alcohol)

Pathophysiology Drugs of abuse are often of low molecular

weight, water-soluble, and lipophilic They are easily transferred across the placenta

to the fetus, and across the blood-brain barrier of the fetus

1/2 life of drugs usually prolonged in the fetus Drugs either bind to CNS receptors, or affect the

release and reuptake of various neurotransmitters

They have long lasting effects on developing dendritic structures and are toxic to fetal cells

Risk Factors Associated with an Increased Incidence of Drug Abuse

Poor socioeconomic circumstances Poor education Teenage mother Poor prenatal care

Other Conditions Associated with Drug Abuse Multiple drug abuse Poor nutritional status Anemia Infectious Disease (Hep B, syphilis, HIV,

and other STDs)

Obstetric Complications Associated with Drug Abuse IUGR Fetal Distress PROM Premature Delivery Chorioamnionitis Specific to cocaine: HTN, cardiac

arrhythmias, CVA, abruption, respiratory arrest, fetal demise

Diagnosis History:

Many drug users withhold informationDetails of the quantity and duration of abuse

are unreliable Labs:

Urine tox only reflects intake from the last few days prior to delivery

False positive immunoassays can occur (i.e. morphine positive if took in poppy seeds or codeine from cold/cough medicine)

More specific chromatography or mass spectrometry may determine the source

Diagnosis Labs:

Meconium analysis reflects drug usage over a longer period and is more sensitive than urine○ Disadvantage = specimen requires processing prior

to testingHair analysis is the most sensitive test available

○ Qualitative relationship exists between amount of drug use and amount incorporated in the hair

○ Newborn hair can be obtained to reflect exposure during last trimester, and can be obtained later should symptoms occur where in-utero drug exposure was previously unsuspected

Diagnosis Physical Exam:

Signs and symptoms vary with the drug(s) used by the mother

Severity of withdrawal may not correlate with dose or duration of drug exposure

Signs and Symptoms

CNSHyperirritabilityIncreased deep tendon and primitive

reflexesIncreased muscle toneTremors and myoclonic jerksHigh-pitched cryWakefulnessSeizures

Signs and Symptoms Metabolic/Motor/Respiratory

FeverMottlingSweatingLacrimationSneezing/congestionMoaningYawningHiccupsIncreased rooting reflexesUncoordinated suck and swallowFailure to gain weightTachypnea/nasal flaring

Signs and Symptoms

GIRegurgitationLoose stools/diarrhea

Diagnosis Patients are usually observed for at least 3-5

days for S/S of withdrawal before they are discharged home

Abstinence scoring is a way to assess withdrawal signs

There are several abstinence scoring systems, but none have been adopted as the standard

The Finnegan scoring system is the most comprehensive and widely usedA score of 7 or less is considered mild withdrawal and

infants do well with non-pharmacologic comfort measuresRepeated scores of 8 or more generally indicate the need

for pharmacologic therapy

Studies On NAS Limitations:

Urine tox screens do not reflect drug exposure throughout pregnancy

Many women who use drugs are multiple drug users, and also drink alcohol and smoke cigarettes

Therefore, it is difficult to isolate the effect of one drug

Opiates Most frequent cause of NAS Onset of symptoms: Minutes after delivery

to 2-3 days of life Clinical course: Variable, can show any of

the s/s mentioned before, s/s can persist up to 3-6 months

Prognosis: Good, minimal teratogenicity, good catch up growth by 1-2 years, most have normal cognitive and motor development at 5-6 years with long term follow-up

Barbiturates

S/S similar to opiates except onset usually later (4-7 days after birth)

Duration of s/s usually 2-6 weeks, but can last as long as 4 months

Benzodiazepines

Not much is known about benzodiazepines

S/S similar to opiate withdrawal Onset: usually not until 1st few days

after birthHowever, there has been a reported

case where s/s started 21 days after birth with chlordiazepoxide use

Alcohol Foremost drug used today Onset: 3-12 hours after delivery S/S: More CNS effects, less severe and of

shorter duration than withdrawal from opiates More concerning is the risk for Fetal Alcohol

Syndrome 35-40% risk in infants born to alcoholic womenrelated to alcohol dosemajor cause of mental retardation today

Fetal Alcohol Syndrome (FAS)

Criteria for FAS:○ Prenatal or postnatal growth retardation○ CNS involvement: developmental delays,

behavioral problems○ Dysmorphic Facial Features: microcephaly,

microphthalmia, short palpebral fissures, poorly developed philtrum, thin upper lip, hypoplastic maxilla

Numerous congenital anomalies are associated with FAS

Many don’t meet the criteria, but present with fetal alcohol effects

Fetal Alcohol Syndrome

Stimulants Less common cause of NAS Usually see s/s that represent the direct

effects of the stimulants themselves Onset/Duration: Within first 72 hours S/S: Tremors, high pitched cry, irritability,

excessive suck, hypertonia, tachycardia Cocaine and Methamphetamine exposed

fetuses have a high rate of spontaneous abortions, stillbirths, IUGR, prematurity, and asphyxia related to placental abruption

Stimulants Cocaine

Causes vasoconstriction and decrease in placental blood flow with consequent fetal hypoxia

Acts as a teratogen because of the vascular effects: CNS & CV anomalies, limb defects, intestinal atresia

Prognosis: ○ Usually there is good catch up growth by 1 year○ There may be speech and behavioral problems

as children get older○ Studies have shown no difference with respect to

intellectual ability in children who were drug-exposed vs. placebo

Stimulants

MethamphetamineWithdrawal symptoms are less severePrognosis: Unclear, may be associated

with neurocognitive deficits

Marijuana

Studies have suggested an increased risk of prematurity and lower birth weight

Prognosis: Higher incidence of ADHD

SSRIs Cause NAS in up to 1/3 of neonates exposed

in utero Onset/Duration: Severely effected present in

1st 48 hours of life and resolve within 48 hours S/S: Tremors, hypertonia, irritability, GI

disturbance, respiratory distressS/S usually self-limited & does not require

pharmacologic intervention Paroxetine with greatest propensity to cause

NAS

Treatment See Nursery Protocol Manifestations of drug withdrawal in

some infants will resolve within a few days and drug therapy is not required

The infant’s withdrawal score should be assessed to monitor the progression of symptoms and adequacy of treatment

Treatment Treatment should always begin with non-

pharmacological measuresSupportive care:

○ Minimize stimulation - keep baby in a darkened and quiet environment if possible

○ Swaddling and positioning - use gentle swaddling and positioning that encourages flexion rather than extension

○ Prevent excessive crying with a pacifier, cuddling, etc.

○ Feeding should be on demand if possible

Treatment

Decision for pharmacologic treatment is based on the infant’s abstinence scores and mechanism of action of the drug that the infant was exposed to

The goal of therapy is to allow the infant to withdraw without excessive excitation that leads to withdrawal symptoms causing discomfort

Treatment

Medication Choices and Doses - Morphine Sulfate: high dose = 80-100 mcg/kg

q4 hrs; low dose = 30-40 mcg/kg q4 hrsMethadone: 0.05 – 0.2 mg/kg q12-24 hrsBuprenorphine: 13.2 mcg/kg/day in 3 divided

dosesPhenobarbital: Loading = 16mg/kg per 24 hrs;

Maintenance = 2 – 8 mg/kg/day in 2 divided doses

Diazepam: 1 – 2 mg q8 – 12 hrs

Treatment

Once a pharmacologic dose has been advanced to its peak to keep patient comfortable, the dose is gradually weaned so the infant can tolerate mild symptoms of withdrawal

The length of time it takes to wean an infant off medication varies from infant to infant

Treatment

Opioid withdrawal using oral morphine sulfate has been shown to be most effective

Dose can be increased by 20% q8 hrs until s/s of withdrawal are controlled Max dose: 0.2mg/kg/dose

Weaning process varies between providersUsually the peak dose is maintained x 72hrs,

then wean by 20% every other day

Treatment

Additional use of Phenobarbital and/or Diazepam is much debated because of added depressant effects on an infant who is already on a narcotic

Phenobarbital mostly used for CNS withdrawal symptomsIt is preferred for non-opiate related NAS

Breastfeeding

Alcohol – Not recommended if use is excessivecan cause drowsiness, diaphoresis, deep

sleep, weakness, decreased linear growth, abnormal weight gain, and decreased maternal milk production

Nicotine – Controversialcrosses into breast milkmay decrease milk production and cause

the baby to have poor weight gain

Breastfeeding

Amphetamine - Not recommendedMay cause irritability and poor sleeping

habits Cocaine - Not recommended

May cause irritability, vomiting, diarrhea, tremors, seizures

Marijuana - No clear recommendationsLimited studies

Breastfeeding

Methadone – Compatible with breastfeedingMost opiates are compatible with

breastfeeding except for heroinMinimal amounts cross into breast milk and

there is poor oral bioavailability Heroin - Not recommended

May cause tremors, restlessness, poor feeding, vomiting

Breastfeeding SSRIs - Generally safe for breastfeeding

Sertraline and Paroxetine have minimal transfer into human milk

Fluoxetine produces significant plasma concentrations in some breastfeeding infants, which can cause:○ colic, irritability, feeding and sleep disorders,

slow weight gainInfants should be monitored for irritability

and poor feeding, or breast milk can be pumped and dumped

Long Term Management

During the first few years, children exposed to drugs in utero can have neurologic problems

This places a difficult child in a difficult environment

Close follow-up and social services involvement may be required