Download Document

Sh. Pourarian
Neonatologist
Epidemiology
A survey in 1985 by the national institute of drug Abuse
(NIDA) showed.
23 million people in U.S. used illicit drugs
250000 women used intravenous drugs
90% of them were in reproductive age
6000-10000 newborns are born to opiate-addicted mother
each year.
Cont.
Epidemiology
Marijuana and cocaine are the most frequently abused
illicit drugs in pregnancy.
Although opioid abuse in pregnancy is less common, but
their effect on mother and her fetus can be life threatening.
In utero exposure to opioids and other drugs may lead to
fetal dependence and fetal and neonatal withdrawal.
Neonatal abstinence syndrome is a term generally applied to
neonatal withdrawal from heroine or methadone, but
similar signs are also seen in withdrawal from other
substances:
Other narcotics, alcohol, benzodiazepines, barbiturates.
Narcotic Drugs
Natural opiates:
Morphine
Codeine
Synthetic opiates:
Heroin
Methadone
Pentazocine (Talwin)
Meperidine (Demerol)
Oxycodone
Morphinone (Dilaudid)
Fentanyl (immovar)
Non- narcotic drugs
 Hypnosedatives
Barbiturate
 Nonbarbiturate sedatives and tranquilizers
Bromide
Chloral hydrate
Chlordiazepoxide (Librium)
Diazepam (Valium)
Ethchlorvynol (Placidyl)
Glutethimide (Doriden)
 Alcohol
Ethanol
 Cocaine (Crack)
Narcotics:
Any natural or synthetic drug that has morphinlike
pharmacologic actions: opiate or narcotic.
Antenatal problems
1. Intrauterine asphyxia:
Still birth, Meconium- stained amniotic fluid
Fetal distress, low apqar score, neonatal aspiration
pneumonia.
 Continuous fetal well being monitoring is needed.
Factors causes fetal asphyxia.
a. Methadone  sleep disturbances ↑REM > quite sleep 
↑ hyperactive  ↑20% in fetal O2 consumption.
b. Fetal withdrawal coincides with maternal withdrawal 
hyperactivity  ↑O2 consumption
Manifestations
Bradycardia, ↑ sys. and dias. BP, continuous deep breathing movement,
neck tone, desynchronization of electrocortical activity.
2. Abruptia placenta, placenta previa, preeclampsia  placental
insufficiency  fetal distress.
3. Meconium stained amniotic fluid
4. Intrauterine infection :
a. life style
b. ↑PROM
CMI
c. Opiates  compromise immune function
d. Venereal dis., Hepatitis, AIDS response
Humoral immune
Neonatal problems
Heroin:
Diacetylmorphine, is a semisynthetic opioid
It has morphinlike properties but it’s crosses CNS more
rapidly.
Deactivated in liver Morphine
Readily across the placenta
30% LBW, 5% SGA (↓No. of cells, normal size)
Direct growth inhibiting effect on the fetus
No increase in congenital anomalies
Cont.
 Heroin injected IV intensifies the risks due to :overdose
acute bact. Endocarditis, Hep. B,C and HIV / AIDS,
infections.
 Heroin is also can snorted or smoked, make the drug even
more attractive.
 Facilitate contraction of sexually transmitted dis.
 ↑Prenatal risks: Extrauterine preg, PLP, PROM, uterine
irritability, breech presentation, antepartum hemorrhage,
toxemia, anemia, bact. Infections, LBW, still birth
Clinical manifestations
50-75% of infants develop withdrawal syndrome.
Onset of symptoms : 24-48 hrs of life, or as late as 4wks,
depend on several factors:
a. The dosage of heroine (<6 mg/day no or mild symptom)
b. The duration of maternal addiction:
(<1y 55%, >1y 73% incidence of withdrawal)
c. The time of last maternal dose:
↑incidence if drug taken within 24 hrs of birth.
Cont.
d. Type and amount of anesthesia or analgesia given to the
mother, maturity and nutritional state of the infant.
 Less RDS due to accelerated lung maturation, surfactant
 Less Hyperbili. Due to induction of GT enzyme.
 Thrombocytosis, ↑ platelet aggregation
 Abnormal TFT: ↑ triiodothyronine and thyroxin levels
 Withdrawal symptoms
Cont.
Methadone
Used for therapy for heroine addicted patient  Block the
euphoric effects.
Placental limitation of transport
Incidence of withdrawal is 70-90%
Higher birth weight, less IUGR< Heroin addicted
Head circumference < 3% percentile
No congenital anomalies
Thrombocytosis, ↑platelet aggregating activity, after the
first week, persisted for 16 wks.
Cont.
Methadone
 Abnormal thyroid function: ↑T3,T4
 The time of onset of withdrawal symptoms depend:
a. The time of the last maternal dose
b. The dosage of drug: if > 20 mg/day  symptoms
 Withdrawal symptoms
 Some infants have late withdrawal, which may be of two
types:
a.
b.
Shortly after birth, improve, and recur at 2-4wks.
Are not seen at birth, but develop 2-3 wks later.
Non-Narcotic Hypnosedatives:
Differences:
In adult:
1.Rate of developing physical dependent not ↑with the drug dose.
2.But ↑with prolonged and continuous administration over months
or years  produce addiction
In newborn
3. Passive addiction in therapeutic dose used by the mother.
4. The withdrawal manifestation: more intense and life
threatening, Convulsion is more frequent
5. Unlike the narcotics, addiction may be induced by physicians.
Barbiturates
Depends on their action classified to 3 groups: ultrashort,
intermediate, long acting
The intermediate- acting are the most abused
The long-acting (phenobarbital) is not abused,
mostly used for insomnia, relief of anxiety,
anticonvulsant, sedation for toxemia
Barbiturate cross the placenta readily
↑Level found in brain, liver, adrenal of fetus
Cont.
The manifestations of W. symptoms are similar but with
diff. onset:
Intermittent type: 1st day
Long acting: 7 days (2-14 days)
 Metabolized in the liver, T ½ is twice in N.B.
 Infants are full term, AGA, Good apqar scores.
 2 stages of phenobarbital withdrawal symptoms:
Acute : irritability, hiccups, mouthing movements
Subacute: voracious appetite, regurgitation, gagging,
sweating, disturbed sleep pattern, last 2-4m.
Cont.
Manifestations of neonatal narcotic
withdrawal
Central nervous system signs
Hyperactivity
Hyperirritability – excess crying, high- pitched outcry
Increased muscle tone
Exaggerated reflexes
Seizures 2-11%
Tremors
Sneezing, hiccups, yawning
Short , non-quiet sleep
Fever
Respiratory sings
Tachypnea
Excess secretions
Manifestations of neonatal narcotic
withdrawal
Gastrointestinal signs
Disorganized, vigorous sucking
Vomiting
Drooling
Sensitive gag
Hyperphagia
Diarrhea
Abdominal cramps (?)
Vasomotor signs
Stuffy nose
Flushing
Sweating
Sudden, circumoral pallor
Cutaneous sings
Excoriated buttocks
Facial scratches
Pressure-point abrasion
Differential diagnosis
1. Metabolic disturbances: ↓ Glu, ↓Ca, ↓ Mg, sepsis
meningitis, S.A Hemorrhage, Infectious diarrhea,
intestinal obstruction.
2. CBC, X-ray, CSF and Blood culture
3. Mothers who took: tricyclic antidepressant and lithium
during pregnancy  toxicity= similar to withdrawal
syndrome
4. Mothers on phenothiazine (chlorpromazine) 
extrapyramidal dysfunction  Tremor, grimace,
↑muscle tone.
Diagnosis
1. Maternal interview:
- Routine interview
- Structural interview
Lab test
Thin – layer chromatography, immunoassay, gas
chromatography,…
a. Urine
- limitations; benefits
- False negative: 32-63% in N.B
b. Meconium
Drug metabolized in liver  bile GI
In urine  Amniotic fluid  GI
- Ideal specimen for drug testing till 3 days
- Sensitive, quantitative, rapid
c. Hair
Mother, neonate: Mostly in chronic users.
Treatment
1. Management of the antenatal and neonatal
complications: Asphyxia, fetal distress, Mec. asp., cong.
Anomalies
* Use of Narcan is contraindicated for birth asphyxia.
2. Routine serologic test: syphilis, HIV, Hepatitis B
Treatment
The goal of Rx
1. ↓ irritability
2. Feeding tolerance without vomiting or diarrhea
3. Sleeping between feedings without sedation
Symptomatic treatment
Supportive care:
Alone or together with pharmacotherapy
a. Quite environment, free from noxious stimuli
b. Tight swaddling, holding, rocking
c. Hand to mouth facilitor pacifier
d. Placing in a slightly darkened quiet area
e. Hypercaloric formula (24 cal/30 ml) as needed
f. Monitoring of temp, HR, RR, Q4h
g. Check for diarrhea, vomiting Q8h
h. Be aware of SIDS
Cont.
‫جدول‬
‫جدول‬
‫جدول‬
 Infants should be scored at first appearance of NAS
 Then repeated every 3-4 hrs based on feeding time
 Pharmacotherapy is based on serial scoring of
withdrawal signs:
8 or higher over three scoring intervals.
12 or higher over tow scoring intervals
If scores > 8 the scores must be checked Q 2hr
If the desired effect has been obtained for 72hrs,
the dosage must be tapered gradually without altering
dosing interval  D/C
B. Medications
1.Neonatal morphine solution (NMS): drug of choice for
narcotic withdrawal
Preparation: 0.4 mg/ml oral morphine dilution:
Add 1 ml of 4 mg/ml inject able solution of morphine + 9 ml
of normal saline.
2. Neonatal opium solution (NOS):
Hydroalcoholic solution 10 mg/ml + 25 Fold sterile water 
0.4 mg morphine / ml
The dilution is stable for 2 weeks
3. Paregoric:
Contains : 0.4 % opium = 0.04% Morphine + other additives
Dose as for NMS or NOS
Cont.
 Dosing scheme for NMS or NOS
Score
8-10
11-13
14-16
17 or greater
NMS or NOS
0.8 ml/kg/d divided Q4h/feeding
1.2 ml/kg/d divided Q4h/feeding
1.6 ml/kg/d divided Q4h/feeding
2.0 ml/kg/d divided Q4h/feeding
Increased by 0.4 ml until controlled
Cont.
a. Increase 2 drop/kg (0.1 ml/kg) Q 3-4 hr
b. If > 2.0 ml/kg/day  add phenobarbital
c. If infant score remain < 8 for 72 hrs.  wean by 10% of
total dose daily.
d. If weaning  score > 8  restart the last effective dose
e. D/C NMS or NOS if the daily dose < 0.3 ml/kg/day
4.Phenobartital
 Is not the drug of choice of opiod withdrawal
 Recommended for anticonvulsant therapy.
 If NAS induced by sedative or hypnotics
 It may used as a second – line drug for NAS when NMS
fails to alleviate the symptoms
 Dose : 20 mg/kg  ↑10 mg/kg Q 8-12 hr /dose 
40mg/kg
Cumulative Sum of loading doses
20 mg/kg
30 mg/ kg
40 mg/ kg
Maintenance phenobarbital
5 mg/kg/d
6.5 mg/kg /d
8 mg/kg/d
* Phenobarbital can be given PO or IM/24hr
* Taper by 10% every day after improving of symptoms
Cont.
5. Morphine and phenobarbital
Infants withdrawing from multiple drugs
NMS dose: 0.05 ml/kg Q 4hr
phenobarbital dose: 10 mg/kg Q12
Tapering of morphine first  then phenobarbital
Less sever withdrawal
Shorter mean duration of hospital stay
Reduced hospital cost.
Cont.
Morphine: 0.1 -0.2 mg/kg can be
effective in the Rx of seizures or
chock due to acute NAS.
6. Chlorpromazine
No longer used because of its side effects.
It is useful to control the vomiting. Diarrhea
Dose: 1.5-3 mg/kg / day Q4h , IM Po
7. Methadone
- Is not used for withdrawal from narcosis
- It is safe for methadone treated mother breast fed.
- Dose 0.1 mg/kg/dose  ↑0.025 mg/kg dose Q4h
8. Diazepam:
Is not used because of side effects 0.1-0.3 mg/kg
IM  till symptoms are controlled.
9. Lorazepam:
Used for sedation alone or with NMS or NOS.
Dose: 0.05-0.1 mg/kg /dose/IV.
Complications
Alterations in serum electrolyte, pH, dehydration
Profound wt. loss
Aspiration pneumonia
Respiratory alkalosis
Neurobehavioral abnormalities
Long term outcome
1. Syndrome of late-onset withdrawal
 2-4 wks of age with or without previous
symptoms
 Similar to early withdrawal symptoms
 Voracious appetite, poor wt. gain for (8-16wks)
Cont.
2. Systemic hypertension
At 2 wks of age  continue  12 wks
3. Child abuse and sudden infant death syndrome
Thermal burns, cigarette burns, traumatic ecchymosis
in first 8 months and 8% ↑incidence of SIDS
Cont.
4. Growth and psychomotor development
 At 12 m. of age not differ from others
 At 3-6 y of age  retardation in Ht, wt, HC
 Neurologic abnormality, poor fine and gross motor
coordination, balance problem, delayed language
development
 Otitis media, abnormal eye movement.
Cont.
- At preschool age
↓ perception, ↓ short term memory, ↓ organization, behavioral
abnormality, aggressiveness, hyperactivity, socioeconomic
problem, poor school performance, no difference in IQ test.
5. Breast feeding
- D/C if the mother has been abused drug continuously
- If she is HIV positive
6. Maternal support
Thanks