Sh. PourarianNeonatologist

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.

MethadoneUsed 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% percentileNo 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. Shortly after birth, improve, and recur at 2-4wks. b. 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 newborn3. 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 signsDisorganized, vigorous sucking Vomiting Drooling Sensitive gagHyperphagia Diarrhea Abdominal cramps (?) Vasomotor signs Stuffy nose Flushing Sweating Sudden, circumoral pallor Cutaneous sings Excoriated buttocks Facial scratches Pressure-point abrasion

Differential diagnosis1. 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

TreatmentThe 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.

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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 NMS or NOS 8-10 0.8 ml/kg/d divided Q4h/feeding 11-13 1.2 ml/kg/d divided Q4h/feeding 14-16 1.6 ml/kg/d divided Q4h/feeding 17 or greater 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 Maintenance phenobarbital 20 mg/kg 5 mg/kg/d30 mg/ kg 6.5 mg/kg /d 40 mg/ kg 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 Q12Tapering 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 outcome1. 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