Neonatal Abstinence Syndrome

            Intrauterine drug exposure, depending on the substance abused, poses differing risks for the fetus and infant.  Outcomes to intrauterine drug exposure generally fall into 1 of 3 categories:

The drug(s) may have a teratogenic effect for the developing fetus and organ systems

The drug(s), if consumed during Central Nervous System development, may be associated with changes in neurobehavior

Abrupt cessation of maternal drug(s) at the time of delivery may produce a withdrawal syndrome.

Withdrawal symptoms can also be experienced by the fetus during maternal abstinence or when the mother attempts to reduce her drug consumption.  Lastly, another way of precipitating Neonatal Abstinence Syndrome (NAS) is iatrogenic, through the administration of potentially addicting substances (e.g. fentanyl) for pain and sedation during the neonate’s hospitalization with the subsequent abrupt withdrawal.  The drug, dose and duration of use determines the extent of withdrawal and symptomatology.  

            The withdrawal syndrome experienced by newborns and seen by many newborn and neonatal nurses  has come to be known as NAS.   The extent of withdrawal and symptomatology varies according to the amount and type of intrauterine drug exposure.  The onset of withdrawal symptoms may vary from minutes to weeks after birth; the majority of the time symptoms will appear within the 1st 72 hours following birth.  During the immediate post-delivery period the newborn may exhibit the following symptoms:

Tachycardia

Tachypnea

Spitting, drooling, hiccups

Hyperirritability, restlessness, tremors

Fist sucking

Disturbed/erratic sleep patterns (increased or decreased)

High-pitched cry

Vomiting, diarrhea, poor feeding

Respiratory distress

Yawning, sneezing

Sweating

Inconsolability

Seizures

Unfortunately, many of the mother's of these infants may be anxious for an early discharge or the facility itself  has an early discharge program.  In these cases, the withdrawal symptoms may not appear until the infant is already at home.  The NAS may go undetected/recognized, ignored and/or place the infant at risk for neglect or abuse.  

 

            It is  well documented in the literature, NAS ordinarily occurs with antenatal opiate exposure but it may also occur with  alcohol, nicotine, sedative and antidepressant exposure, although our knowledge of specific correlations remain limited.   About ¾ of the infants exposed to these substances antenatally will develop a withdrawal syndrome.  In some cases, cocaine for example, the NAS is relatively short-term and usually doesn't require pharmacologic intervention or delay hospital discharge.  On the other hand, opiate withdrawal is more likely to produce a longer and more life-threatening syndrome.   Opiate withdrawal usually appears 3-5 days after birth but can persist from 2-3 weeks to as long as 4-6 months.  In rare cases, symptoms can persist for upwards of a year.

           The long-term effects of substance use in the infant population is sometimes difficult to attribute to the substance abuse itself.  Family genetics, ongoing maternal drug- and/or life-style, socioeconomic factors, abuse and support systems all play a role and must be considered when interpreting/documenting causative findings.  Having said that, listed below are several adverse long-term effects to in utero substance exposure.  Remember direct relationships may not be well established.

Decreased birthweight, length, head circumference—after 2 years of age, only a shorter length continued

Delayed ability to sit up

Increased tone

Excessive movements 

 Decreased motor coordination and balance—disappears/diminishes after 7-12 years

Shortened attention span/learning disabilities

 Poor motor skills/coordination 

Poor impulse control/self-regulation

Behavioral/management difficulties

Speech/language delays

Strabismus/nystagmus 

           The aim of NAS interventions is to ameliorate the physiologic and psychologic effects the infant is experiencing.   Often times, in short-term, mild withdrawal syndromes, non-pharmacologic interventions are sufficient.  Examples of non-pharmacologic interventions may include (not all inclusive):

Rocking/using a swing

Swaddling

Holding

Decreased environmental stimuli/quiet environment

Low lighting

Minimal handling

Nonnutritive sucking/pacifier use

On-demand feedings

If these interventions are unsuccessful or ineffective, the infant may suffer weight/fluid loss or risk neglect or abuse (if at home) and further interventions are warranted.  

            Approximately ½ of exposed infants will require pharmacologic intervention.  For those requiring pharmacologic intervention an over-time comprehensive and objective assessment/scoring tool addressing the specific systems of concern/involved is necessary. Various such scoring tools are available; the choice of a specific tool remains up to each facility but should be consistently used throughout the nursery areas.  These tools can confirm the diagnosis of NAS, assess the onset, progression, and/or resolution of symptoms and aide in determining necessary pharmacologic intervention.   Tabulated results can also be useful in monitoring the infant’s response to pharmacologic interventions.  

Drugs to consider when treating NAS:

Paregoric

 1st compounded in 1700s.  Remained the drug of choice until recently, despite no studies to support its use

Use has declined due to known and potential toxic effects of its ingredients

 

Phenobarbital

Used for drug withdrawal other than opiates and for maternal poly-drug use

Controls the CNS symptoms but not the GI symptoms

Large doses may depress the CNS delaying mother-infant attachment and may interfere with suck

No studies have shown phenobarbital to have an  advantage over chlorpromazine, diazepam or methadone

 

Tincture of opium 

10 mg/ML 

(contains  0.4 mg/mL Morphine equivalent)

Controls CNS symptoms and minimizes GI disturbances

Adjust dose based on weight and tabulated results of assessment tool

As symptoms are controlled or diminish, dose is tapered to a  sub-therapeutic level and then discontinued

 

Oral Morphine

2 and 4 mg/mL

Contains no additives and is ~ 10 % alcohol

Dose calculated to deliver to the full-term infant the same quantity of morphine equivalent to that supplied by paregoric

 

Diazepam (Valium)

Does help control CNS symptoms but not as effectively as Tincture of Opium.  

Concerns for the infant:  difficult to metabolize and excrete, sleepiness, poor suck, late-onset seizures, additional ingredients/preservatives in parenteral form.

While other benzodiazepines are widely used in adults, they have not been sufficiently studied in the neonatal population.

 

Clonidinine

An a2 (alpha) agonist used to treat hypertension, tics and ADHD.  Recently its was used to control the withdrawal symptoms from substances such as nicotine, alcohol, and narcotics.  In one small trial, some of the infants had a reversal of symptoms with one dose

It may be administered orally (reconstituted tablets) or with transdermal patches.  A commercially prepared oral liquid is not available at this time.  

Skin irritation may be associated with the patches.  

The oral version (tabs) must be initiated at the lowest possible dose and titrated slowly due to its sedation and cardiovascular effects.  Likewise, when discontinuing it must be tapered slowly to prevent rebound hypertension.

 

Chlorpromazine Controls both CNS and GI symptoms

Eliminated very slowly in the neonate with a reported half-life of 3 days.  This prolonged excretion time coupled with its side effects (cerebellar dysfunction, hematologic problems) limits its usefulness in the neonatal population. 

 

Dextromethorphan (N-methyl D-aspartate [NMDA]) A receptor blocker, studied in adults, that decreased the physical symptoms of opioid withdrawal and was well tolerated.  

Whether this will show continuing promise in the neonatal population remains to be determined.

 

  

           In addition to non-pharmacologic and/or pharmacologic interventions,  other infant-care areas need to be addressed as well:

  1. Nutrition:   Close monitoring of and adequate weight gain and head circumference growth cannot be stressed enough.  While the infant may indicate frequent hunger and an active-to-hyperactive suck, feeding remains a challenge.  Despite adequate calorie intake the infant may continue to loose weight due to his hypermetabolic state; infants with severe withdrawal symptoms lose more weight than their healthy counterpart and take longer to gain it back.   High-calorie formulas are recommended with frequent or on-demand feeding schedules.

Breastfeeding is made on an individual basis.  If the mother is continuing to use cocaine, marijuana, opiates, amphetamines, or phencyclidine it should be avoided.  In 2001, the American Academy of Pediatrics (AAP) revised its stand on breastfeeding and methadone use to allow it.  Research data suggested that at even high maternal doses of methadone the amount of methadone found in the breastmilk was minimal and no clinical effects had been noted.

  1. Environment:  NAS infants have limited self-regulating, state control and deep sleep capacities.  Therefore, both medical and nursing care should be coordinated around feeding times to allow for prolonged periods quiet or sleep.  Quiet, soothing music is a useful adjunct to encourage and maintain sleep and limit arousal states.   Place the infant in an  area/room with dim lighting and where alarm soundings are minimal.  If the later is not possible, prompt response to silencing of alarms will minimize disruption of sleep and quiet states. 

  2. Narcan (Naloxone) Concerns have been raised about the use of narcan and its safety following a narcan-induced case of seizures in a newborn  whose mother had used methadone within 8 hours of delivery.   To date, other than this one (1) reported case, data are not readily available about adverse outcomes following the use of narcan in narcotic-exposed infants.  At this time, the AAP states that the administration of narcan to the infant of the narcotic-dependent women, or women whose status is questionable, may result in neonatal seizures due to abrupt drug withdrawal.  In addition, they caution hospitals to consider avoiding narcan administration to minimize precipitating withdrawal.

Many substances abused by the pregnant woman have the potential for precipitating NAS in the newborn.  The type and amount of substance used as well as the duration of use all affect both the number and severity of withdrawal symptoms in the newborn.  If supportive interventions are not successful, pharmacologic agents may be needed.  The choice of pharmacologic agent(s) should be infant-specific, based on clinical presentation; tabulated results from the assessment/scoring tool; and the infant's overall condition.   All of these issues need to be evaluated to maximize outcomes for the infant.

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