MATERNAL & NEONATAL WITHDRAWAL SYNDROME BY: Dr. F.Goudarzi Clinical Toxicologist SUMS

MATERNAL & NEONATAL WITHDRAWAL SYNDROME

BY:Dr. F.Goudarzi

Clinical ToxicologistSUMS

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TREATMENT OF THE PREGNANT WOMAN MEANS THAT ONE IS CARING FOR

TWO PATIENTS, NOT ONE

* IT IS SUGGESTED THAT PHYSICIANS ADDRESS THE ISSUE OF ALCOHOL AND DRUG USE DURING PREGNANCY WITH ALL

WOMEN OF CHILD BEARING AGE

What is MNAS?

Presence of withdrawal behaviors in neonates exposed to dependency-producing substances in utero.

These behaviors include central nervous hypersensitivity, gastrointestinal dysfunction and vague autonomic symptoms.

25-40 % of infants with known exposure are asymptomatic or display only mild symptoms

Substances that can cause MNAS Opiates- (55-94% of neonates exposed in

utero will have withdrawal symptoms) Alcohol Tobacco Benzodiazepines Barbiturates SSRIs (neonatal behavioral syndrome) ?Amphetamines ?Cocaine ?Marijuana TCA

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SEDATIVE/HYPNOTICS

BENZODIAZEPINE &PHENOBARBITAL WITHDRAWAL• NO DIFFERENCE BETWEEN PREGNANT AND NON-PREGNANT

WOMAN, ALTHOUGH SEVERE WITHDRAWAL CAN PRODUCE STATUS EPILEPTICUS AND FETAL RESPIRATORY ARREST

• CAN LAST 3 TO 5 WEEKS• VERY MUCH LIKE ACUTE ALCOHOL WITHDRAWAL• TIME COURSE AND SEVERITY DEPEND ON

• DOSE OF DRUG• DURATION OF USE (DOES NOT WORSEN AFTER ONE YEAR OF

USE)• DURATION OF DRUG ACTION

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FETAL EFFECTS FROM BARBITURATES

CLEFT PALATE HYPOSPADIAS (PENILE ORIFICE IS

TOO LOW) MICROCEPHALY (SMALL HEAD SIZE) SHORT NOSE

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FETAL EFFECTS FROM BENZODIAZEPINES

????CLEFT LIP AND PALATE

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OPIOIDS

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OPIOIDS WITHDRAWAL IN THE MOTHER –EARLY & MIDDLE PHASE

RESTLESS SLEEP DILATED PUPILS ANOREXIA GOOSEFLESH IRRITABILITY TREMOR

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OPIOIDS WITHDRAWAL IN THE MOTHER - LATE PHASE

INCREASE IN ALL PREVIOUS SIGNS AND SYMPTOMS INCREASE IN HEART RATE INCREASE IN BLOOD PRESSURE NAUSEA AND VOMITING DIARRHEA ABDOMINAL CRAMPS LABILE MOOD DEPRESSION MUSCLE SPASM WEAKNESS BONE PAIN

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OPIOIDS WITHDRAWAL

IT IS NOT RECOMMENDED TO TAPER PREGNANT WOMEN OFF OF METHADONE, BUT THE SAFEST TIME IS THE 2ND TRIMESTER (TIPS2)• BEFORE 14 WEEKS AND AFTER 32

WEEKS THERE IS AN INCREASED INCIDENCE OF SPONTANEOUS ABORTION AND PREMATURE LABOR

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OTHER WITHDRAWAL AGENTS CLONIDINE

• NO TERATOGENIC EFFECTS• LONG TERM USE NOT RECOMMENDED

BUPRENORPHINE• APPEARS SAFE WITH NO TERATOGENIC

EFFECTS, BUT NOT APPROVED FOR USE YET ( JONES AND JOHNSON 2001)

NEVER USE NARCAN UNLESS AS A LAST RESORT• SPONTANEOUS ABORTION• PREMATURE LABOR• STILLBIRTH

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FETAL EFFECTS OF OPIOIDS

LOW BIRTH WEIGHT FETAL DISTRESS PREMATURITY NEONATAL ABSTINENCE SYNDROME STILLBIRTH SUDDEN INFANT DEATH SYNDROME MECONIUM ASPIRATION

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NEONATAL ABSTINENCE SYNDROME

60-80% OF OPIOIDS EXPOSED INFANTS• 72 HOURS AFTER BIRTH

• CNS EFFECTS• IRRITABILITY• HYPERTONIA (INCREASED MUSCLE TONE)• HYPERREFLEXIA• ABNORMAL SUCK• POOR FEEDING• SEIZURES ( 1 TO 3%)

• GI EFFECTS• DIARRHEA • VOMITING

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METHADONE DOSING STRATEGIES IN THE PREGNANT WOMAN

INITIAL 10 TO 40 MG EXTRA 5 TO 10 MG IN 3 TO 4 HOURS IF

SIGNS AND SYMPTOMS OF WITHDRAWAL

REPEAT 5 TO 10 MG Q 3 TO 4 H PRN STABILIZE AT THIS DOSE FOR SEVERAL

DAYS DECREASE BY 2 .5 MG Q 7 TO 10 DAYS

AND MONITOR OB STATUS

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NEONATAL ABSTINENCE SYNDROME

MEDICATION DOSING

INDUCTION TITRATION STABILIZATION TAPERING

TINCTURE OF OPIUM 0.1 ML/KG (2 DROPS/KG) Q 4 H WITH FEEDINGS

INCREASE BY 0.1 ML/KG Q4H AS NEEDED

Q 4 H WITH FEEDINGS FOR 3 TO 5 DAYS

TAPER GRADUALLY BY REDUCING DOSE NOT FREQUENCY

PAREGORIC (0.4 MG/ML)

0.1 ML/KG ( 2 DROPS/KG) Q 4H WITH FEEDINGS

INCREASE BY 0.1 ML/KG Q 4H PRN

Q4H WITH FEEDINGS FOR 3 TO 5 DAYS

TAPER GRADUALLY BY REDUCING DOSE NOT FREQUENCY

METHADONE 0.05 TO 0.1 MG/KG Q 6H

INCREASE BY 0.05 MG/KG Q 6 H PRN

WHEN STABLE, GIVE TOTAL DAILY DOSE ONCE DAILY OR ½ BID

TAPER GRADUALLY TO 0.05 MG/KG, THEN D/C MED

Diagnosis

Maternal history of drug use Positive identification of substance in

maternal or neonatal specimen Scoring

Once diagnosed- consult social services

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TIME TO ONSET OF MATERNAL WITHDRAWAL SIGNS

*MATERNAL WITHDRAWAL DEPENDS ON THE DRUG, FREQUENCY OF USE, AND DURATION OF USE. TIMES CAN VARY SIGNIFICANTLY.

DRUG TIME

ALCOHOL 6 to 60 HOURS

BARBITUATE 4 to 10 DAYS

DIAZEPAM 1 to 12 DAYS

OPIOID 12 to 72 HOURS

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TIME TO ONSET OF NEONATAL WITHDRAWAL SIGNS

USUALLY THE ONLY WITHDRAWAL SYNDROME THAT REQUIRES TREATMENT IS OPIOID WITHDRAWAL

DRUG TIME

ALCOHOL 3 to 12 HOURS

BARBITUATE 4 to 7 DAYS

DIAZEPAM 1 to 12 DAYS

OPIOID 48 to 72 HOURS

Clinical Presentation

Onset of symptoms varies with the substance being used by the mother, the quantity, frequency and duration of intrauterine exposure, timing and amount of the last maternal use, as well as maternal and infant metabolism and excretion

CNS Tremors, irritability, increased

wakefulness, high-pitched crying, hypertonicity and hyperactive reflexes, seizures, yawning, sneezing and skin excoriation

Gastrointestinal• Poor feeding, uncoordinated

and constant suck, vomiting or regurgitation, diarrhea, dehydration

Autonomic Signs• increased sweating. Nasal

stuffiness. Rhinorrhea, mottling, temperature instability, fever, tearing

W - wakefulnessW - wakefulnessI - irritabilityI - irritabilityT -tremors, twitching, tachypneaT -tremors, twitching, tachypneaH - hyperventilation, hypertonia, H - hyperventilation, hypertonia,

hyperpyrexia,hyperpyrexia, hyperaccusis, hiccupshyperaccusis, hiccupsD - diarrhea, diaphoresis, D - diarrhea, diaphoresis, R - rub marksR - rub marksA - alkalosisA - alkalosisW - weight lossW - weight lossA - apneaA - apneaL - lacrimation, L - lacrimation, S - seizures (myoclonic), sneezing, skin S - seizures (myoclonic), sneezing, skin

mottlingmottling

Frequency of Clinical Signs

Disturbed sleep – 53% Mottling 53% Excess sucking 45% Tremors 43% Tachypnea – 43% Hypertonia 41% Fever 40% Seizures 2-11% (often later)

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STIMULANTS

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STIMULANTS

WITHDRAWAL IN THE MOTHER• DYSPHORIA• FATIGUE• UNPLEASANT DREAMS• INSOMNIA• HYPERSOMNIA (INCREASED SLEEP)• INCREASED APPETITE• PSYCHOMOTOR RETARDATION• AGITATION

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MATERNAL EFFECTS OF STIMULANT AND COCAINE

ABRUPTIO PLACENTAE PREMATURE LABOR SPONTANEOUS ABORTION DECREASE DURATION OF DELIVERY GREATER NUMBER OF OBSTETRICAL

COMPLICATIONS

NAS

video clip

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ALCOHOL WITHDRAWAL

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MATERNAL WITHDRAWAL

THE RATE OF ALCOHOL METABOLISM MAY BE FASTER DURING PREGNANCY, SO BE AWARE THAT WITHDRAWAL CAN START SOONER THAN EXPECTED.

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MINOR WITHDRAWAL IN THE MOTHER

TIME• 6 to 60 HOURS

SYMPTOMS• TREMORS• INSOMNIA• NAUSEA• ANOREXIA• ANXIETY• WEAKNESS

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MINOR WITHDRAWAL IN THE MOTHER

SIGNS• ACTION TREMOR• INATTENTION• EASY STARTLE• PLETHORA• CONJUNCTIVAL INJECTION• INCREASED REFLEXES

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EARLY WITHDRAWAL IN THE MOTHER

TREATMENT• WATCH FOR DT’S• EVALUATE FOR OTHER ILLNESSES AND

INJURIES• LIGHT SEDATION WITH

BENZODIAZEPINES• THIAMINE• ELECTROLYTE BALANCE• PATIENTS MUST UNDERSTAND THAT

THEY NEED FURTHER TREATMENT

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LATE WITHDRAWAL IN THE MOTHER

DELIRIUM TREMENS• HIGH RISK FOR DT’S IF BLOOD ALCOHOL LEVEL GREATER THAN 300 mg%

OR WITHDRAWAL SEIZURES• PROFOUND CONFUSION AND MISPERCEPTIONS• DISORIENTATION• HALLUCINATIONS• PARANOID DELUSIONS• MOTOR HYPERACTIVITY

• TREMOR, RESTLESS, AGITATED, INCREASED REFLEXES• AUTONOMIC HYPERACTIVITY

• INCREASED HEART RATE, PROFUSE SWEATING, DILATED PUPILS

• MORTALITY OF THE MOTHER IS 10 to 15% IF UNTREATED, 1 to 2% IF TREATED

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FASD

BINGE DRINKING (5 OR MORE DRINKS ON ONE OCCASION) IS ESPECIALLY DETRIMENTAL TO THE FETUS

THERE IS NO PROVEN “SAFE” AMOUNT OF ALCOHOL TO USE DURING PREGNANCY• ALCOHOL HAS BEEN FOUND IN BREAST

MILK

NICOTINE AND TOBACCO

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NICOTINE AND TOBACCO

IF THE PREGNANT WOMAN CANNOT STOP SMOKING USING BEHAVIORAL INTERVENTIONS, THEN NICOTINE REPLACEMENT PRODUCTS CAN BE USED

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NICOTINE WITHDRAWAL SYMPTOMS IN THE MOTHER

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

AnxietyIrritabilityPoor conc.RestlessCravingGI prob.HeadacheDrowsy

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CANNABINOIDS

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CANNABINOIDS

WITHDRAWAL IN THE MOTHER• 10 HOURS AFTER USE

• TREMOR OF THE TONGUE AND EXTREMITIES

• INSOMNIA• SWEATS• LATERAL GAZE NYSTAGMUS• EXAGGERATED DEEP TENDON REFLEXES

MNASS

Used to initiate, adjust and wean pharmacologic

treatment. Scoring should begin within 4 hours after birth and

continue every 4 hours until the onset of symptoms. At the onset of symptoms scoring should be done every 3 hours for 24 hours and then every 4 hours for the duration of treatment.

Observation should be made after feedings, newborns must be awake and calm to asses muscle tone, respirations and Moro reflex. Newborns should be observed for 20 to 30 minutes before scoring is determined.

Management

Supportive• Swaddling ( decreases the

added stimulation of startled movements)

• Reduction of environmental stimuli ( decreased light and noise)

• Frequent small feeding • Frequent diaper change are

necessary to reduce skin excoriation

• Monitor intake, output and weigh daily to assess hydration and caloric status related to vomiting, diarrhea and poor feeding status.

Pharmacologic intervention is indicated for evidence of acute withdrawal such as seizures, poor feeding (excess weight loss), severe diarrhea, vomiting, dehydration, inability to sleep and fever not due to any infectious etiology

• 3 consecutive NAS scores of 8 or more or the average of 3 consecutive NAS scores is 8 or more.

• or 2 consecutive NAS scores of 12 or more or the average of 2 consecutive score is 12 or more.

• Pediatric consult is recommended when considering pharmacologic treatment.

• Cardio respiratory monitoring.

Pharmacologic Therapies in Neonatal Abstinence Syndrome

Paregoric • 0.2-0.5 ml/dose q 3-4 p.o. or 4-6

drops q 4-6h; may increase by 2 drops until clinical improvement

• Improves most of the withdrawal symptoms especially diarrhea, taper dose by 10-20% per day over 2-4 week after symptoms stable for 3-5 days.

Neonatal Opium Dilution 0.4% solution (contains 0.4 mg morphine equivalent per ml) guidelines:

• 0.8 ml/kg/day for NAS 8-10• 1.2 ml/kg/day for NAS 11-13• 1.6 ml/kg/day for NAS 14-16• 2.0 ml/kg/day for NAS >16• Doses given orally every 3-4 h

with feeds ( not prn)

Phenobarbital• 15-20 mg/kg/day loading dose

to achieve level of 20-40 mg/ml. Maintenance dose =2-8 mg/kg/day.

• Taper dose by 10-20% per day after symptoms stable for 3-5 days.

Diazepam• 0.3-0.5 mg/kg q 8 h; initial dose

i.m then p.o• Allows rapid suppression of

symptoms, decreased suck, avoid in jaundice or premature infants.

Pharmacologic Therapies in Neonatal Abstinence Syndrome

Methadone• 0.1-0.5 mg/kg/day divided q

4 to 12 h• Increase by 0.05mg/kg/dose

until symptoms are well controlled

• Taper dose by 10-20% per day over 1 mo

• Treatment usually longer (5 days-4 mo)

• Long half-life (26 h )

Chlorpromazine• 0.5-0.7 mg/kg/dose loading

then 2-2.8 mg/kg/day in divided doses q 6 h

• Decrease dose over 2-3 wk

Clonidine• 0.5-1 ug/kg single dose

then 3-5 ug/kg/day divided dose q 4-6 h

• Increase by 0.5 ug/kg over 1-2 days until maintenance dose is achieved

Weaning Guidelines

Once NAS are consistently 6-8, maintain the same therapeutic dose 48 hours before weaning. Wean by 10% of maximum dose every 1-2 days. If symptoms increase, return to effective dose. Therapeutic agents should be gradually decreased over a 2-6 week

period. Neonatal opium solution should be weaned first, then Phenobarbital.