Neonatal abstinence syndrome (NAS) refers to withdrawal symptoms in newborns exposed to drugs in utero. NAS is most commonly associated with opioid exposure and presents as central nervous system disturbances, gastrointestinal issues, and autonomic dysfunction. Diagnosis is based on clinical history and signs, with supportive care as first-line treatment and pharmacotherapy with morphine or other drugs as needed. Proper management aims to stabilize the newborn and facilitate healthy development.

1. Dr. Mazen A.M Abuanza
SQUH – NNL
2013

3. Outlines:
Introduction.
Definition.
Substances used or
misused.
Incidence.
Pathophysiology
Clinical Presentation
Diagnosis.
Differential Diagnoses.
Treatment.
Complications.
Follow up.

4.  Neonatal Abstinence Syndrome (NAS) is a syndrome
of drug withdrawal observed in infants of mothers
physically dependent on drugs.
Also known as Neonatal withdrawal syndrome or
Neonatal passive addiction.
Introduction

5.  Two major types of neonatal abstinence
syndrome are recognized:
1. Prenatal NAS secondary to maternal use of substances
that result in withdrawal symptoms in the newborn.
2. Postnatal NAS secondary to discontinuation of
medications such as fentanyl or morphine used for pain
therapy in the newborn.

6. Postnatal NAS results when an abrupt discontinuation
of opioid analgesia occurs, usually after prolonged drug
exposure.
Fentanyl/Morphine are the most commonly used analgesic
drugs in the neonatal intensive care unit (NICU).

7.  It is a potent, rapid-acting, synthetic opioid.
 Tolerance and physical dependence are thought to develop
more rapidly with:
1. Shorter acting drugs.
2. Continuous infusions rather than with intermittent administration.

8. Clinical studies have found that continuous infusions of
fentanyl and morphine produce a high rate of opioid
withdrawal when administered to critically ill infants.
Tolerance and withdrawal symptoms may occur after 5 or
more days of continuous infusion of these drugs.

9. Maternal substance abuse, is a leading causes of preventable
mental, physical, and psychological problems in infants.
Substance use by pregnant women has both medical and
developmental consequences for the newborn.

10. Definition of NAS:
Neonatal abstinence syndrome (NAS) is a syndrome
of drug withdrawal with non specific signs and
symptoms that may occur in babies following
in-utero or postnatal drug exposure.

11. Substances used or misused
A large variety of substances may be used or misused by
women of childbearing age.
The following major classes of drugs may lead to neonatal
withdrawal:
1. Opioids.
2. Central nervous system (CNS) stimulants (amphetamines,
cocaine, selective serotonin reuptake inhibitors (SSRIs)
3. CNS depressants (alcohol, barbiturates, benzodiazepines)
4. Hallucinogens.

12. Drugs frequently associated with neonatal problems

13. Incidence
The incidence and severity of NAS varies.
Different definitions, screening, assessment and
diagnostic tools used in different countries complicate
the reporting of substance use.

15.  It is estimated that 60-90 % of infants born to substance using
mothers will develop signs and symptoms of NAS, and of these
50-75% will require treatment.
The incidence of drug exposed infants has increased 300% since
the 1980s

16. Pathophysiology

17. Most illicit drugs cause an addiction in both the
mother and the infant.
 Addiction or tolerance is due to passage of the drugs
across the placental barrier; this occurs in varying
degrees.
Substances that act on the CNS are usually highly
lipophilic and have relatively low molecular weight.

18.  Once drugs cross the placenta, they tend to accumulate in
the fetus because of the immaturity of the renal function
and the enzymes used for metabolism.
Disruption of the transplacental passage of drugs at birth
results in the development of a withdrawal syndrome.

19. CLINICAL PRESENTATION
The onset and the severity of symptoms are dependent on:
1. The specific drug
2. Maternal metabolism
3. Drug history (including the timing of the most recent use of
drug before delivery)
4. Placental transfer of drug
5. Infant metabolism and excretion.

20. Timing of withdrawal symptoms
Timing of withdrawal varies.
In infants exposed to heroin (short half-life), withdrawal symptoms
often begin within 24 hours of birth, whereas methadone usually
begins 24 to 72 hours after birth.

21. However, for opioids, withdrawal may be delayed until five days of age
or later .
If one week or longer has elapsed between the last maternal opioid use
and delivery of the infant, the risk of neonatal withdrawal is low.

22. Clinical findings observed in NAS:
Central nervous system:
Tremors
Irritability
Increased wakefulness
High-pitched crying
Hypertonicity
Hyperactive reflexes
Seizures
Yawning
Sneezing
Skin excoriation due to excessive rubbing.

23. Seizures are reported in 2 to 11 % of infants
withdrawing from opioids.
In addition, abnormal electroencephalographic (EEG)
changes have been reported in over 30 % of neonates
withdrawing from opioids.

24. Gastrointestinal :
Poor feeding
Uncoordinated and constant sucking
Vomiting or regurgitation
Loose or watery stools
Dehydration.

25. Autonomic/metabolic signs:
Increased sweating
Nasal stuffiness
Fever
Temperature instability
Tachypnea
Mottling of the skin

26. Premature infants
Premature infants <35 weeks gestation are at a lower risk for
developing withdrawal symptoms compared with term infants.
Possible explanations:
I. Developmental immaturity of the preterm central nervous system
II. Reduced total drug exposure during the intrauterine period
III.Lower amounts of fat deposition of drug
IV.Difficulty in identifying symptomatic premature infants because
assessment tools were developed for more mature infants

27. DIAGNOSIS
1. Clinical diagnosis
2. Neonatal testing

28. 1- Clinical diagnosis
The clinical diagnosis is based upon a history of Maternal
substance abuse and Neonatal findings that are consistent
with NAS by abstinence scoring methods .

29. 2- Neonatal testing
Detect the presence of specific drugs can be performed in a variety of
biological specimens (eg, urine, hair, blood, and meconium).
Blood and urine screening of the newborn have a low sensitivity.
Testing of neonatal hair is challenging because of difficulties in
quantifying the small amount of drug and the slow growth of hair in
the fetus/neonate.
Meconium analysis is sensitive and specific for drugs (including
opioids).
Testing of umbilical cord tissue by using drug class-specific
immunoassays.

30. Scoring systems
Several abstinence scoring methods(eg, Lipsitz tool, Finnegan
scoring system, and the neonatal withdrawal inventory)
It developed based upon the clinical manifestations of NAS.
These tools measure the severity of neonatal withdrawal and are
used to initiate, adjust, and wean pharmacologic therapy.

31. The most widely
used system is the
Finnegan scoring
System.
The Finnegan scoring
system assesses 31
specific clinical items
and is the one used in
our practice.

32. DIFFERENTIAL DIAGNOSIS
 Because other neonatal problems may have similar features to the
NAS, clinical signs should not be attributed only to withdrawal
without appropriate assessment and diagnostic tests.
1. Hyperthyroidism
2. Hypocalcemia
3. Hypoglycemia
4. Sepsis
5. HIE
6. Polycythemia.

33. MANAGEMENT
Goals — The main goals of therapy are:
1- To establish consistent weight gain, which followed by
obtaining adequate sleep and nutrition.
2- And to integrate the infant into a normal social
environment .

34. The management approach includes:
1- Supportive nonpharmacologic care.
2- Pharmacologic therapy.
The decision to initiate pharmacologic therapy is based on:
1- The severity of symptoms, which is typically determined by
abstinence scoring systems.
2- The response to nonpharmacologic supportive measures.

35. Supportive care
The initial treatment of NAS should be supportive, as it can
avoid or reduce the amount of pharmacologic therapy,
which prolongs hospitalization.

36. Supportive care includes :
Decreased sensory stimulation (eg, quiet room and swaddling the
infant).
Administration of small frequent feedings.
Administration of high caloric formula (24 cal/oz) or fortified breast
milk (for mothers on methadone) to supply additional calories.
Skin care The best approach to prevent skin excoriation due to
excessive rubbing is to swaddle the infant, thereby reducing trauma to
the skin

37. Ongoing assessment of the response to nonpharmacologic
care includes:
1. Monitoring weight and readjusting dietary intake to
ensure appropriate growth.
2. Poor weight gain with adequate caloric intake may reflect
the need to introduce pharmacologic intervention.
3. Monitoring temperature stability, sleeping patterns, and
gastrointestinal symptoms.

38. Breastfeeding
Breastfeeding is encouraged in mothers who adhere to a
supervised drug treatment program as long as their infant
continues to gain weight.

39. Parental role
 To facilitate ongoing care involve parents in the assessment
and management.
 Ensure parents receive appropriate:
1. Feeding information.
2. Social support.
3. Information regarding settling techniques.
4. Developmental care of baby.
5. Risks of environmental tobacco smoke exposure.

40. Pharmacologic therapy
Pharmacologic intervention is aimed:
1- At the short-term improvement of clinical
symptomatology.
2- At Long-term benefits from treatment remain unproven.

41. Pharmacologic therapy is generally started for the individual
neonate when he or she has three or more consecutive
scores above 8 despite adequate supportive care
Indications for drug therapy in infants with NAS include:
I. Seizures
II. Poor feeding with failure to gain weight
III. Inability to sleep despite adequate decreased environmental
stimuli
IV. Fever unrelated to another source
V. Significant diarrhea and/or vomiting.

42. Treatment and Weaning
Pharmacologic therapy
 Oral morphine sulfate is the most effective
 Phenobarbital and diazepam

43. Oral morphine sulfate
Low dose regimen
 0.03-0.04mg/kg every 4 hours.
High dose regimen
 0.08-0.1mg/kg every 4 hours
Maximum dose
 0.2mg/kg/dose

44. Phenobarbital and diazepam
 Preferred for non opiate withdrawal especially CNS
irritability
loading dose 16mg/kg/day
Maintenance dose 2-6mg/kg/day BID

45. Weaning, Simple approach:
 Maintain the same dose for 72 hours
 Decrease the dose by 10-20% every other day

46. Complications
Birth defects
Low birth weight
Premature birth
Small head circumference
Sudden infant death syndrome (SIDS)
Respiratory depression

47. Follow-up
Babies who required monitoring and/or medication for management of
NAS should receive:
Medical review within one week of discharge
Withdrawal symptoms may continue after discharge and after
medication ceases (e.g. Hypertonicity and poor feeding).
Babies discharged whilst still receiving medication require:
hospital clinic follow-up at least weekly until after the medication
has been ceased

48. Note:
Babies born to women receiving usual doses of
opioid for pain relief during labour and birth,
are not considered to be at risk of withdrawal from
that exposure.

49. Note:
Do not administer Naloxone to babies of known
or suspected opioid dependent women during
resuscitation or the neonatal period.
It may precipitate severe rapid onset of
withdrawal associated with seizures.