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)
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.Methadone sleep disturbances REM > quite sleep hyperactive 20% in fetal O2 consumption.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 its 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 (
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.
MethadoneAbnormal thyroid function: T3,T4The 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: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 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
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 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 diagnosisMetabolic disturbances: Glu, Ca, Mg, sepsis meningitis, S.A Hemorrhage, Infectious diarrhea, intestinal obstruction. CBC, X-ray, CSF and Blood culture Mothers who took: tricyclic antidepressant and lithium during pregnancy toxicity= similar to withdrawal syndromeMothers on phenothiazine (chlorpromazine) extrapyramidal dysfunction Tremor, grimace, muscle tone.
Maternal interview: - Routine interview - Structural interview
Lab test Thin layer chromatography, immunoassay, gas chromatography,a. Urine - limitations; benefits - False negative: 32-63% in N.Bb. 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 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 irritability Feeding tolerance without vomiting or diarrhea Sleeping between feedings without sedation
Symptomatic treatment Supportive care:Alone or together with pharmacotherapy Quite environment, free from noxious stimuli Tight swaddling, holding, rocking Hand to mouth facilitor pacifier
d. Placing in a slightly darkened quiet area e. Hypercaloric formula (24 cal/30 ml) as neededf. Monitoring of temp, HR, RR, Q4hg. Check for diarrhea, vomiting Q8hh. Be aware of SIDS
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. Medications1.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 controlledCont.
Increase 2 drop/kg (0.1 ml/kg) Q 3-4 hrIf > 2.0 ml/kg/day add phenobarbital If infant score remain < 8 for 72 hrs. wean by 10% of total dose daily.If weaning score > 8 restart the last effective dose D/C NMS or NOS if the daily dose < 0.3 ml/kg/day
4.PhenobartitalIs not the drug of choice of opiod withdrawalRecommended 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 symptomsDose : 20 mg/kg 10 mg/kg Q 8-12 hr