OBST 7010 Week 8 Review (Swan)

Chemicals, Drugs and Toxins in Pregnancy

General Considerations
 Effect of drug/chemical on fetal tissue depends on:
o Time of administration / gestational age
o Duration of exposure
o Dosage
o Type of chemical agent
o Genetic makeup: mother, fetus
o Coexistence of other chemicals & interaction with chemicals in question

Periods of Vulnerability
 1st 13 days gestation is “all-or-none” – Conceptus either killed or not affected
 Organogenesis occurs 13-56 days from conception (or days 31-71 since LMP)
o Chemical insult may produce congenital anomaly (or teratogen)
o Fetus vulnerable during remainder of pregnancy to drugs, infections, or toxins
o May damage intellectual or behavioral capacities as well
 Birth process – Neurological damage often occurs prior, during the immediate neonatal period, or in the first few weeks
 Complexity of absorption, distribution, or excretion between the mother and fetus
o Maternal physiological changes in pregnancy:
 Increased blood volume
 Dilutional hypoalbuminemia
 Changes in regional blood flow
o Fetus is in compartment once removed from maternal system
o Due to fetal circulation, drug distribution may vary in different situations
 Hypoxia:
o DEC peripheral & hepatic circulation
o INC concentrations in fetal brain or heart
o DEC binding of drug by fetal plasma proteins than adult, resulting in more free drug available to fetus
o Effect of body water content (94% 4 months; 76% term)
o Fetal fat: None in early pregnancy (15% body wt. at term)
 Routes of fetal elimination
o Placenta is the primary organ of excretion fetal wastes
o Fetal kidney
o Fetal skin
o Fetal lungs
o Passage of chemicals via fetal urine, skin or lungs may allow them to be recirculated, added to, or preferentially
partitioned in fetus or amniotic fluid
 Anomalies may not be detected until later in life
o 2-3% congenital anomalies
o 7.5% at 1 year

Identification of Chemical Abuse

 May be difficult: Role of denial in addictions
 Depression/ nervousness during visits
 For example, depression/anxiety/irritability--amphetamines
 Bruises, possible domestic violence (usually denied)
 Needle tracks
 Pain intolerance
 History of chronic pains requiring narcotics (in a ”flare-up,” wants meds)
 Alcohol, smoking, insomnia
 History of past and present abuse
 Family and social relations
 Father may be a user or supplier
OBST 7010 – Drugs in Pregnancy (Swan) | 1
  Problems with law enforcement, neighbors, family
 Fetal/prenatal child abuse
o Deliberate use of fetotoxic drugs/chemicals by the mother
o Criminal prosecution cases

Commonly Used Drugs: Alcohol, narcotics, tranquilizers, phencyclidine HCL (PCP or “angel dust”), tetrahydrocannabinol (THC)

Addiction – The use of something outside of oneself substance/ chemical/ person/ relationship/ activity) as a way to mood-alter to
avoid feelings/ pain

Alcoholism
 2% of women abuse alcohol in pregnancy
 4+ drinks/day
 Fetal alcohol syndrome – Occurs in 30-40% alcoholic mothers
o Noted in 40% infants where 6 drinks (6 OZ.)/day 1st trimester
o Craniofacial abnprmalities: low forehead, small upturned nose, sunken nasal bridge, broad upper lip, short palpebral
fissures, lowset ears, receding chin
o Cardiac, brain, spine abnormalities
o IUGR, mental retardation
o 17% perinatal mortality

Smoking
 Decrease in birth wt. (about 200 gm) with as few as 10 cigs/day
 DEC head circumference/body length >15 cigs
 Time of greatest influence = last 4 months
o DEC oxygenation of fetus – formation of carboxyhemoglobin
o DEC uterine blood flow (secondary to nicotine effect on ut. vascul.)
 Correlated to serum cotinine (a major nicotine metabolite) & LBW
 High cadmium, INC placental Zn, DEC fetal RBC Zn (trapped)
 Fetus experiences DEC oxygen, spinning, dizziness (regression)
 INC spont. abortion and perinatal mortality
 Nicotine/cotinine in cervical mucus – INC risk cervical CA

Marijuana
 Prevalent in younger population
 Dose of delta-9-THC varies 0.5-2.0%
 No current pregnancy associated risk?
 Fetus can get stoned

Amphetamines
 CNS stimulation, anorectic, prevent sleepiness
 No evidence of teratogenicity
 Symmetrical IUGR in one study

Caffeine
 Additive effect of >300 mg/day in smoking >15 cigs/day

Cocaine (Crack)
 Incidence 8-9.8% +
 Norepi causes vasoconstriction – INC BP, tachycardia
 Dopamine: euphoria, addictive effects
 Metabolites can be detected in maternal urine
 Crosses placenta by simple diffusion
o Can detect in neonate’s urine to 4 days if used <72 hrs delivery
 Assoc. w/ poor obstetric outcomes, high parity, lack of PN care
 Numerous effects on infant:
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 o 25% risk preterm delivery in addicted mothers
o 20% SGA
o Asymmetrical fetal growth retardation (DEC head circumference)
o PROM, meconium staining
o Behavioral problems (esp. irritability), low threshold for hyperstimulation
o Kidney malformations; intestinal atresia
 ACOG recommendations:
o Question all preg. patients on initial PN visit as to drug use/abuse
o Counsel users about effects & offer support to abstain
o Periodic urine testing throughout preg. to check abstinence
o Urine testing for hypertensive pts, placental abruption, IUGR

Benzodiazepines
 Valium: no teratogenicity
 Given to mother near time of delivery, but causes fetal hypothermia

LSD – Causes no teratogenicity

PCP (Angel Dust) – 40% growth retardation

Narcotic Drug Addiction

 Increased incidence over past 15 yrs.
 Risk factors due to:
o Minimal PN care
o History of using more than 1 drug
o Poor nutritional status
o Anemia, poor wt. gain, 30-50% IUGR
o Use of drugs of variable potency
o Unknown effects from adulterants mixed w/drugs
 Hepatitis/HIV where needles shared
 Infections at needle sites & other organs due to DEC host defense
 Increased incidence STD’s
 Withdrawal symptoms:
o Early: twitching, tremulousness
o Later: sweating, yawning, lacrimation, rhinorrhea, restlessness, dilated pupils, myalgia, muscle twitching, fever,
tachycardia, tachpnea, anorexia, nausea
o Eventually: extreme restlessness, abdominal pain, vomiting, hypertension, diarrhea
o Signing out “AMA” after delivery to get drugs
o Pregnant narcotic addict must continue to use heroin or methadone
 If she stops, fetus may undergo withdrawal and die in utero
 Complications
o Meconium staining of amnionic fluid -due to fetal hypoxia & episodes of withdrawal
o PROM, prematurity, LBW
o Toxemia, fetal malposition, placental abruption
o Stillbirth, puerperal morbidity
 Treatment goals:
o Avoid withdrawal
o Methadone maintenance program
o Close monitoring of neonate for signs of withdrawal

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