Transcript No Slide Title

The effect of maternal drug use on
the neonate
N. Ambalavanan MD, FAAP
Neonatologist
Purpose of this presentation
To
help you understand the prevalence and
risks of drug use in pregnancy
To help you identify the infants at higher
risk of drug exposure in fetal and neonatal
life
To understand the basis of management of
drug exposed infants
Exposure of the fetus to drugs
 Concepts:
The uterus is NOT a fully protected environment for the
fetus, either physically or chemically. Almost every
substance used by the mother passes to the fetus.
 The fetus is the highest animal in the food chain.
 Disorder of organ or structure formation can occur only
in the first few weeks of pregnancy (<12 weeks) when
organs are forming, while changes in size or destruction
of structures are possible in the subsequent months.
 Drugs can also cause intellectual or functional disorders.

Drugs in pregnancy
 Classification:
Substances not generally considered drugs: alcohol,
cigarettes, coffee, solvents, various chemicals etc.
 Non-prescription drugs: E.g. aspirin, ibuprofen
(Advil/Motrin), vitamins, products from health food
stores etc.
 Prescription drugs: E.g. antibiotics, anti-epileptic drugs
etc.
 Drugs of abuse / Illegal drugs: E.g. cocaine, heroin,
amphetamines, marihuana etc.

The use of drugs in pregnancy
Although the use of illegal drugs attracts considerable
attention, the use of legal drugs and of alcohol or cigarettes
is far more widespread.
 Pregnancy is a symptom-producing event, and pregnant
women usually consume more drugs (and food).
 A World Health Organization Survey (1991) of 14,778
women from 22 countries showed that 79% received an
average of 3.3 drugs (not including OTC drugs or
alcohol/tobacco).

The use of drugs in breast-feeding
mothers
 Breast

feeding is resurgent:
1930’s :80% breast-fed --> 1950’s: 50% -->
1970’s: 20% -->1990’s: 50%
 Breast
feeding superior to formula feeds
(nutritional, immunologic, and psychological
properties), but also carries maternal drugs to baby.
Substances not generally considered drugs:
 Alcohol
Alcohol
is teratogenic --> Fetal Alcohol Syndrome (FAS)
 Incidence:
 1/300-1/2000 (depending on population): Avg. 1/500
 30-40% of neonates of alcoholic mothers affected.
 Most common recognizable cause of mental retardation
 Incidence of alcohol abuse in pregnancy may be increasing
in recent years (0.7-->1.4%). 20% of alcoholics are women.
 Even 1-2 drinks daily (30 cc of absolute alcohol) in early
pregnancy may lead to FAS, but 4-5 drinks (60-75 cc) are
usually required to cause FAS. No safe limit established.
Fetal Alcohol Syndrome
At least one feature from each of three categories:
1. Prenatal and postnatal retardation - with small-for-age
weight, length, and/or head circumference.
2. CNS disorders with signs of abnormal brain functioning, delays in
behavioral development, and/or intellectual impairment.
3. At least two of the following:
abnormal craniofacial features - small head, small eyes or
short eye openings, or a poorly developed philtrum (the grove above
the upper lip), thin upper lip, short nose, or flattened mid facial area.
Fetal Alcohol Effects
Alcohol exposed babies that do not meet all these criteria for FAS.
Alabama: General population
Alcohol and Alabama (1997)
%
of mothers who drank before pregnancy: 39%
(42% white, 33% black)
 % of mothers who drank during pregnancy: 3.6%
(4% white, 2.7% black)
This 90% reduction suggestive of awareness of danger
 % low birth weight: 7.4% if drinking before
pregnancy, 9.6% (30% increase) if drinking during
pregnancy
Alcohol and breast feeding
 Alcohol
passes freely into breast milk, but acute effects on
infant are rare. Chronic effects are uncertain.
 American Academy of Pediatrics : Alcohol is usually
compatible with breastfeeding. Breastfeeding infants of
mothers who regularly use alcohol should be closely
monitored.
 Infants prenatally exposed to alcohol may have weaker
sucking responses
 Heavy drinking by the mother can decrease her milk
supply, as well as inhibit the milk-ejection reflex.
Tobacco
 More
than 1 in 8 women (13.6%) smoke during
pregnancy. 1 in 6 (17.2%) pregnant teens smoke.
 Heavy smokers are unlikely to stop during
pregnancy
 Nicotine (decreases blood flow to placenta and
causes fetal hypoxia), carbon monoxide, cyanide etc
are among the 4000+ constituents of cigarette
smoke that may be hazardous.
Effects of smoking in pregnancy
Increase in low birth weight (proportional to number of
cigarettes) (LBW in Alabama FY 1997: 10.7% in smokers vs.
5.3% in non-smokers (White), and 15.3% vs. 12.8% (Black).)
 40% higher perinatal death (4800 deaths/yr in the US)
 Spontaneous abortion: 1.2x /10 cigarettes (141,000/yr)
 Active and passive smoking is a risk factor for PPHN.
 Significant decrease in IQ (even at 6 yrs age) in multiple
studies.
 Smoking linked to 2700 SIDS deaths/yr in the US alone.

Effect of CSE on PASMC proliferation
(*p<0.05 vs. control, ANOVA and Dunnett's test)
150
*
*
100
*
*
CSE 1:5
CSE
CSE 1:50
0
CSE 1:500
50
Control
Cell counts at 72 hrs
(% control at 0 hrs)
200
Caffeine: Coffee, Tea, Cola
 One
of the most popular “drugs” in the world.
 One cup coffee =70-100 mg, tea 40-50 mg, cola 3040 mg caffeine
 Fetal levels are similar to maternal levels, and may
alter fetal sleep patterns
 Moderate consumption (1-2 cups coffee/day) are
probably safe. High doses (>5-6 cups/day) may
cause spontaneous abortion, difficulty in becoming
pregnant, and possibly lower birth weight.
Non-prescription drugs
 Aspirin:
The most commonly ingested drug in pregnancy. In 8
surveys of >50,000 patients, aspirin was consumed in
>30,000 (61%).
 Can cause bleeding, prolonged labor, prolonged gestation
in mom. Low dose maternal aspirin (<150 mg/day) may
be safe to baby. Higher doses may cause PPHN and
bleeding in neonates and should be avoided in pregnancy.
 To be used with caution during lactation (small amount in
breast milk)

Non-prescription drugs (contd.)
 Ibuprofen
(Advil/Motrin): May lead to PPHN,
prolongation of pregnancy. To be avoided in pregnancy, esp
3rd trimester. Safe during breast feeding.
 Acetaminophen
(Tylenol): Safe for short-term use in
regular doses. Toxic at high doses to mom and baby.
Compatible with breast feeding.
 Anti-histamines
e.g. Diphenhydramine (Benadryl):
Possibly safe (some reports of malformations). C/I during
lactation (babies are sensitive to antihistamines)
Non-prescription drugs
 Avoid
anti-diarrheal agents, laxatives. Anti-acid
agents e.g Ranitidine (Zantac), Famotidine (Pepcid)
are generally safe.
 Diabetics and asthmatics need special attention.
Some drugs cause more problems.
 Avoid vaccines unless they are essential.
 Avoid cough medicines, diuretics.
 Avoid hormones esp. steroids and their derivatives
(health food stuff like DHEA), radiation
Non-prescription drugs (contd.)
 Vitamins:
Folic Acid: Essential vitamin - prevents NTDs.
Necessary to take if considering pregnancy!
 Vitamin A: High doses cause malformations. Acne
medications (isotretinoin) are very dangerous. Vitamin A
is essential, but not more than 8,000 IU/day.
 Vitamin D: High intakes may be associated with
supravalvular aortic stenosis.
Use of multivitamins up to RDA is recommended. Megadoses may cause problems and should be avoided.

Prescription drugs
 Risk
varies with drug ingested, dose, stage of
pregnancy, interactions with other drugs, individual
variation etc.
 Risk of not taking the drug versus risk of taking the
drug needs to be considered.
 Many drugs have not been studied in adequate detail
in pregnant humans (extrapolation from animal
studies useful only to a point), so current knowledge
is unreliable. (Catch-22 situation)
Prescription drugs
 Antibiotics:
Most penicillins/cephalosporins are
usually safe. Quinolones (e.g. Ciproflox),
aminoglycosides (e.g. Streptomycin, Gentamycin)
are to be avoided.
 Anti-hypertensives: ACE inhibitors (Captopril,
Enalapril) are usually avoided.
 Anticonvulsants: Valproate, Phenytoin etc can cause
malformations.
Illegal drugs (drug abuse): National
More than 5 million American women of childbearing age
use illicit drugs (1 million use cocaine, 3.8 million
marijuana)
 7.5% of women in labor (+) for at least one drug (Rhode Island

Dept of Public Health)
15% of pregnant women in Florida (+) for alcohol or drug
use
 Prevalence of drug use similar in different areas of the
country, regardless of hospital or size of population

Illegal drugs (drug abuse) in Alabama
Positive screen in 12.9% of women (11% in pregnant,
15.6% in those not pregnant)
 No difference urban (12.8%) vs. rural (13.1%)
 No difference “high-risk” vs. “low-risk” obstetric groups
 + marijuana > in whites (16%) and non-pregnant (14%)
vs. black (7.1%) and pregnant (9.3%) women
 + cocaine screen > in non-white (1.9%) and single (1.8%)
vs. white (0.9%) women
 No difference in + cocaine screen between trimesters

(Am J Obstet Gynecol 1991; 165:924-7. n=5010, of which 2970 pregnant)
Identification of substance abuse
It is a misconception that substance abuse occurs only in
lower socio-economic groups
 Many pregnant women are unaware of adverse effects that
may occur, and may not volunteer a history of illicit drug
use if they fear that their baby and other children may be
taken away from them
 It is the responsibility of the health care team to identify,
educate, counsel, and manage pregnant women and their
neonates with substance abuse problems

Identification of illicit drug use
 Patient-reported
history not adequate: sensitivity
6.3%, specificity 98%
 Tobacco and alcohol use pattern: sensitivity better
(16.4%) but still not adequate
 Suspected preterm labor: 17% (+) UDS (cocaine
10% )
Benefit
vs. cost and pitfalls of universal
screening?
Suggested guidelines for drug screening of
the neonate
 Urine,
meconium, or hair analysis should be
performed if:
A) Mothers have a history of any one of:
1) H/o of drug abuse in present or past pregnancy
2) Limited prenatal care (<5 visits in term infants or onset
of PNC at >18 wks GA in preterm infants)
3) H/o of Hepatitis B, HIV, Syphilis, Gonorrhea
4) H/o prostitution
5) Unexplained placental abruption / premature labor
Suggested guidelines for drug screening
of the neonate
B) Infants who exhibit any one of the following:
1) Unexplained neurological complications (e.g.
intracranial hemorrhage/infarction, seizures)
2) Evidence of possible drug withdrawal ( e.g. hypertonia,
irritability, trembling, muscle rigidity, constipation or
diarrhea)
3) Unexplained IUGR
( modified from Wagner et al: The impact of prenatal drug exposure on the neonate:
Obstet & Gynecol Clin North Am 25 (1):169-194, 1998)
How effective is screening?
 Urine

Drug Screening (UDS) most often used:
Can detect cocaine (up to 8 hrs in mom, 72 hrs in baby),
opiates (morphine and heroin up to 48 hrs),
amphetamines (48 hrs), barbiturates (short acting 48 hrs,
long acting 7 days), and benzodiazepines (variable). (Can
also be used to detect marijuana and alcohol but not usually done)
 Meconium
analysis: meconium is a reservoir for drugs
from 18 wks GA to delivery. However, more expensive
($90 vs. $20 for UDS) and technically difficult.
 Hair
analysis: Useful till 3 months age. Timing possible.
Marihuana (pot/joint/reefer)
sativa. 400 chemicals. 61 cannabinoids. D9-tetrahydrocannabinol (THC) main agent.
 Second commonest substance abused (after tobacco).
 Seriousness underestimated since it is not usually
considered a “hard” drug
 Difficult to estimate effect of Marihuana alone
(polydrug use, variation in amount smoked,
differences in strength of cigarettes, social factors)
 Cannabis
Marihuana : effects on the baby
 No
definite proof of malformations
 May be associated with growth retardation
 May be associated with abnormal neurological
development (inconsistent finding)
 May be associated with prematurity (very doubtful)
 Effects more likely to occur with heavier use
Cocaine (crack/coke)
 Alkaloid
derivative of Erythroxylon coca
 Inhibits re-uptake of sympathomimetics
(Epinephrine, NE, DA), causing rapid heart rate,
hypertension, vasoconstriction
 Cocaine easily passes into fetus through placenta
 Decreases blood flow to uterus, decreases fetal
oxygenation and intestinal blood flow.
Cocaine: effects on the baby
 Lower
birth weight, smaller head size (smaller
brain), shorter length, greater risk of IUGR, and
genito-urinary and cardiac defects
 Lower scores on neonatal and childhood
developmental exams
 Increased risk for necrotizing enterocolitis, even in
term babies
 Increased risk for SIDS
 Increased risk for cerebral stroke/hemorrhage
Amphetamines (Meth/crystal/rock)
 Stimulant
drugs which work in a manner similar to
cocaine
 Problems similar to cocaine/polydrug use: LBW,
prematurity, abruption, neonatal withdrawal. Case
series of congenital brain hemorrhage/infarction.
 Lower scores in neurodevelopment (infancy) and
aggressive behavior (at 8 yrs of age) noted.
 LSD often diluted with amphetamines. Direct effect
of LSD alone difficult to determine.
Morphine/Heroin/Methadone/Demerol
 9000
babies are born to narcotic addicts each year in
the US. In 1992, 88,000 women were using heroin
regularly.
 Withdrawal symptoms are the main risk (40-80%).
Symptoms: Abnormal sleep pattern, irritability,
seizures, fever, sweating, tachypnea, sneezing,
excessive sucking, poor feeding, loose stools,
vomiting. Symptoms may occur much later and last
longer (2-30 days) with methadone
Narcotics: effects on the baby
 Increased
incidence of low birth weight, IUGR,
prematurity.
 2-4 fold higher risk for SIDS
 Long-term developmental abnormalities (lower
scores on IQ & language tests even when placed in
foster homes)
 Associations include an increased risk for sexually
transmitted diseases, hyperbilirubinemia, and poor
social situation (true for all drugs of abuse)
Management of the drug-exposed neonate
 More
general than specific:
Decreased environmental stimulation
 Swaddling
 Darkened environment
 Small frequent feeds

 Withdrawal
symptoms: Phenobarbital often used. If
exposed to only opiates, tincture of opium/paregoric can be
used
 Social evaluation a MUST! Improvement of future social
environment the best long-term treatment.