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Neonatal Abstinence Syndrome (NAS)

Lisa Patel, MD and Solomon Behar, MD
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20:19

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Lisa Patel and Sol discuss the symptoms, diagnosis, and treatment of neonatal drug withdrawal.

Pearls

  • Opioids easily transfer across the placental and blood brain barrier.  To develop NAS, an infant must be prenatally exposed for about a month or longer.  Term infants have a higher risk for NAS.

  • NAS has a spectrum of presentations; seizure is one of the most serious presenting signs.

  • Nonpharmacologic treatments, such as swaddling, rooming-in and higher-calorie on demand feedings,  are becoming used more frequently as first line treatments.

 

  • How many babies have neonatal abstinence syndrome (NAS)?  A New England Journal of Medicine paper estimates that between 2003 and 2014, there has been a sevenfold increase in the number of NICU days due to withdrawing infants.

Tolia VN et al.  Increasing incidence of the neonatal abstinence syndrome in the U.S. neonatal ICUs.  N Engl J Med. 2015 May 28;372(22):2118-26. PMID 25913111

  • Can you have NAS with drugs that are not opiates?  Historically, NAS has referred to a postnatal opioid withdrawal syndrome.  However, babies can show signs of withdrawal from other substances, like benzodiazepines, barbiturates and alcohol.  Marijuana is reported as a common drug being used or abused during pregnancy; it does not appear to cause withdrawal symptoms in the baby.   Subtle long term neurobehavioral outcomes have been described.

Editor’s note: It is prudent to note that polysubstance use is common and can complicate the clinical picture.  

  • How do opiates cause NAS?  Because of their chemical properties, opioids easily transfer across the placental and blood-brain barrier.  The fetus, therefore, has prolonged exposure to the drug in utero and a subsequent sudden discontinuation at birth.  Term infants, as opposed to preterm infants, have a higher risk of NAS because they tend to have more fatty deposits in which the drug is stored.  Additionally, there is increased fetoplacental transfer later in gestation.  Infants need at least 1 month of exposure to be at risk for NAS.

Editor’s note: Interestingly, there may also be a genetic component to NAS.  Specifically, there is variability in the mu-opioid receptor and this may have an effect on opioid tolerance.

Raffaeli G et al.  Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies.  Pharmacotherapy. 2017 Jul;37(7):814-823. PMID 28519244

  • What is the clinical presentation of NAS?  NAS can have a spectrum of presentations.  Seizure is one of most severe presentations.  Of course, it is important to think of other causes for the infant displaying these symptoms; be it seizure, tachypnea, sweating, and/or hypothermia.  Specifically, hypoglycemia, hyperthyroidism, hypoxic-ischemic encephalopathy, infection and/or polycythemia should be considered in the differential.  A CBC and blood culture should be obtained prior to the initiation of any treatment.

  • What is a withdrawal score?  The finnegan scale is the most widely used withdrawal scoring system in the US.  It is broadly divided into 3 categories;

    • 1) CNS disturbances,

    • 2) metabolic, vasomotor or respiratory disturbances, and

    • 3) GI disturbances.  

 

Some CNS disturbances include a high pitched cry, a disrupted sleep-wake cycle, a hyperactive Moro reflex, evidence of tremors, increased muscle tone and/or myoclonic jerks (distinguished from seizures by placing a hand on the infant’s limb to extinguish the behavior).  The high pitched cry is very distinctive.  

 

Some metabolic, vasomotor or respiratory disturbances include increased sweating, hypothermia, tachypnea,  frequent yawning, nasal stuffiness or sneezing.  

 

Some GI disturbances include excessive sucking, poor feeding, regurgitation, loose stools and/or projectile vomiting.

    • Most hospitals use a modified Finnegan Scale to come up with a score.  Generally, if an infant score has 24 points or higher over 3 scoring periods and/or the infant is having lots of loose stool, poor feeding, dehydration and/or poor weight gain, pharmacologic treatment is started.

      • The time between scoring varies by hospital.  Generally, babies are scored at 4, 8 and 12 hours of life.  However, a baby who is withdrawing from heroin, for example, may not show any signs until 24 hours and a baby withdrawing from methadone may not show any signs until 48 hours.

        • Early initiation of scoring systems are done in babies with known prenatal exposures.

  • How do you test for prenatal drug exposures?  Samples can be obtained from cord blood, baby’s urine or meconium/stool and checked for metabolites.  Obtaining these samples can be difficult with a resistant family.

    • In some circumstances, urine toxicology testing for the mother is also performed.  If there is a strong suspicion of drug use, many hospitals will start scoring the infant while awaiting these tests results.   

  • What are some non-pharmacologic treatments for NAS?  There is really good evidence than non-pharmacologic interventions are effective in reducing NICU stays and decreasing hospital costs.  Additionally, avoiding pharmacologic treatments avoids potential adverse reactions from medications, like apnea.  Generally, any environment that does not overstimulate the infant is ideal.

Holmes AV et al.  Rooming-In to Treat Neonatal Abstinence Syndrome: Improved Family-Centered Care at Lower Cost.  Pediatrics 2016 Jun;137(6).  PMID 27194629

  • Swaddling, gentle handlings, dim lights and low noise can be used to manage the symptoms of NAS.

  • Given the higher caloric needs of babies with NAS, frequent on-demand feedings with high calorie formula and/or thickened feeds can be useful.

  • Additionally, rooming- in with the mother and active maternal participation are some of the best non-pharmacologic tools.  It is important from the beginning to have a non-judgemental constructive relationship with mothers to help facilitate their participation in the infant's care.

  • For women who are on methadone, breastfeeding is beneficial for those infants and can prevent severe NAS.  The amount of methadone in breastmilk is low and therefore, the AAP and ACOG support this recommendation.

    • Drug use itself is not a contraindication to breastfeeding.  To find out more about what other medications are safe to take while breastfeeding a resource, such as Medications and Mother’s Milk can be useful.  Of course, clinical judgement should be used and if there is concern in that there is a lack of disclosure of use and/or co-morbid psychiatric conditions, a child protective services referral may be placed.  In these cases, the infants are generally given formula.   

Editor’s note:  Another good resource for medications that may or may not be safe to use while breastfeeding is Lactmed.

  • How is pharmacologic treatment initiated?  Oral morphine is the most popular starting medication.  The starting dose is 0.04 mg/kg and can be titrated up between 10-20% to get the baby to a stable score on whatever withdrawal scale is being used.  The max dose is 1.2 mg/kg/day and if the infant is not comfortable on this dose, a second line medication, like phenobarbital, is used.  Addition of a second line agent is rare.

    • Once medication is initiated, withdrawal scores are assessed every 4 hours.  Once the infant is at a stable dose of medication, the infant generally stays at this dose for a few days before down titrating about about 10% every 1-2 days until the dose is 0.02 mg/kg/dose.  The oral morphine is then discontinued and the infant is scored for another day or two to make sure he/she is stable off the medication.

  • What other medications can be used?  A recent New England Journal of Medicine paper looked at the use of sublingual buprenorphine in infants compared to the use of oral morphine.  The authors concluded that the infants who received sublingual buprenorphine had shorter lengths of stay and had no increase in adverse effects.  It was a small study but the evidence is encouraging.  The theory is that buprenorphine  has a slightly longer half life and therefore, the peaks and troughs are probably not as severe.  

Grossman MR et al.  Buprenorphine for the Neonatal Abstinence Syndrome.  N Engl J Med. 2017 Sept 7;377(10):996-7. PMID 2880503

  • Is naloxone ever given in situations of respiratory depression with NAS treatment?  No.  It is understood in the treatment of withdrawal that naloxone should not be given as it can precipitate seizure.  If the infant is experiencing respiratory depression, other supportive measures should be given.  

  • What are the long term outcomes of NAS?  A study out of Australia looked at 1 million children over a 13 year period and found that children with NAS had a higher likelihood of being re-hospitalized for potentially preventable conditions, like injuries from burns or poisonings.  Additionally, these children had a 36-fold higher rate of admissions for accidents.  Therefore, close social service follow up is extremely important.

    • Visual disturbances, such as strabismus and nystagmus are higher in opioid affected children, although the mechanism is not completely clear.

Uebel H et al.  Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome.  Pediatrics 2015. Oct; 136(4):e811-20.  PMID 26371197

What is the usual disposition for these children?  While the exact numbers are hard to assess, if a mother has disclosed her drug use, social work but not always child protective services (CPS)  is involved.  If a mother has not disclosed her use but it becomes clear the infant was exposure, a CPS referral is warranted.  The ultimate disposition, then, is at the discretion of CPS.  

Geoffrey R., MD -

In addition to the Hale book “Medications and Mother’s Milk” that Dr Patel references, NIH has the LactMed website (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm) available. BTW, I am often troubled by finding versions of Hales book several editions old on the nursery floor - should try to have most recent version.

Solomon B., MD -

Thanks for the resource Geoff! Agreed- definitely need the latest book!

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Wax On, Wax Off Full episode audio for MD edition 175:26 min - 82 MB - M4AHippo Peds RAP October 2017 Written Summary 439 KB - PDF