Teratogens

A substance, organism, physical agents or

deficiency state capable of inducing abnormal
structure or function such as:
Gross structural abnormalities
Functional deficiencies
Intrauterine growth restriction
Behavioral aberrations

Drug Transfer to the Fetus

Placental transfer may occur by:

Passive diffusion
Facilitated diffusion

Active transport
Placental surface area
Placental metabolism

Drug Passage into Breast Milk

Diffusion from maternal plasma into milk
Higher maternal plasma levels mean higher
breast milk concentrations

Equilibrium will be established with most

drugs between milk and plasma

Drug Transfer
Across Placenta
Molecular weight

Into Breast Milk

Molecular weight

Lipid solubility

Lipid solubility

Ionization

Ionization

Protein binding

Protein binding

Chemical Structure

Drug concentration

Drug equilibrium

STADIUM EMBRIOGENESIS
Week II- late week VIII
Most sensitive stadium

Organ development

STADIUM FETOGENESIS
Late week VIII
Growth and development stadium
Histogenesis CNS

DRUGS GIVEN AFTER THE

FIRST TRIMESTER
1. Heparin
- Vertebral compression fractures
- Osteoporosis
2. Warfarin
- Bleeding into the fetal brain
3. Anticonvulsants
- Neonatal coagulation defect
- Sedation

Cloramphenical
- Gray baby syndrome
- Cardiovascular collapse
5. Tetracycline
- Tooth discoloration
- Enamel hypoplasia
- Bone dysplasia
6. Aminoglycosides
- Fetal ototoxicity
4.

7. Sulfonamide
- Neonatal jaundice
- Hemolytic anemia
8. Ciprofloxacin
- Fetal cartilage damage
9. -Blockers
- Intrauterine growth retardation,
hypoglycemia, hypotension,
bradycardia, death

PHARMACOKINETICS
1. Molecular Size

- 250-500 can cross easily

- 500-1000 cross with more
difficulty
- Greater than 1000 cross very
poorly

2. Lipid solubility
- Lipophilic drugs readily cross placenta
(thiopental)

3. Ionization
- Highly ionized cross the placenta
slowly (succinylcholine,tubocurarrine)
- anionized is highly lipid soluble

4. Protein binding
Only unbound drug is capable of
crossing the placenta
Drugs with low protein binding reach
higher concentrations in the fetus than
mom
Ex: Ampicillin, digoxin

PHARMACODYNAMIC
1.

Maternal drugs action

- The effect of drugs on the reproductive tissues
(breast, uterus) are changed by pregnancy.
- The effect on the maternal tissues (heart, lungs,
kidneys, CNS) are not changed by pregnancy

2. Therapeutic drugs actions in the fetus

- Corticosteroid
lung maturation
- Phenobarbital
Jaundice is lower
3. Predictable toxic drugs action in the fetus
- Chronic use of opioids
- ACE-inhibitor
- Diethylstilbestrol
4. Teratogenic drugs actions

DRUGS IN THE FIRST

TRIMESTER
Anticonvulsants
Poor growth, nail hypoplasia, microcephaly,
cleft lip or palate
2. Phenytoin
- Craniofacial
- Limb
- Growth deficiencies
1.

3. Sodium valproate
- CNS
4. Carbamazepine
- Craniofacial
- Fingernail
5. Sex hormone
- Cardiac defects
- Multiple anomalies

6. Lithium
- Cardiac defects
7. Warfarin
- Condrodysplasia punctata
- Microcephaly, spontaneous abortions
- Facial anomalies
- Several anomalies of CNS
8. Retinoic acids
- Craniofacial, cardiac, CNS

Drug classification for pregnancy

Category A
Controlled studies in pregnant women fail to

demonstrate a risk to the fetus in the first trimester

with no evidence of risk in later trimester.
EX: Paracetamol

Category B
Presumed safety based on animal studies, with no

controlled studies in pregnant, or animal studies have

shown an adverse effect that was not confirmed in
controlled studies in women in the first trimester and
there is no evidence of a risk in later trimesters
EX: Penicilline

Category C
Studies in women and animals are not available or

studies in animals have revealed adverse effects on the

fetus and there are no controlled studies in women.
Drugs should be given only if the potential benefits
justify the potential risk of the fetus
EX: Corticosteroid, Vitamin D, Vitamin B12

Category D
There is positive evidence of human fetal risk (unsafe),
however in some cases such as a life-threatening illness
the potential risk may be justified if there are no other
alternatives
EX: Warfarin, Fenitoin, Sodium Valproat, Diazepam,
obat kanker

Category X
Highly unsafe, risk of use outweighs any potential
benefits. Drugs in this category are contraindicated in
women who are or may become pregnant
Alkohol, Isotretionin, Estrogen, Androgen, and life
vaccine

Penicillins
Category B in pregnancy

the placenta easily and rapidly

Concentrations equal maternal levels
Cross

Lactation
Crosses in low concentrations
Compatible with breastfeeding

Antivirals
(acyclovir, famciclovir, valacyclovir)
Pregnancy Category B
Acyclovir and valacyclovir readily cross the
placenta
Can be used for HSV treatment and suppression

Lactation
Acyclovir and valacyclovir are compatible
Famciclovir should be avoided

Aminoglycosides
(amikacin, gentamicin, tobramycin)
Pregnancy Category C
Rapidly cross placenta
Enter amniotic fluid through fetal circulation

Lactation
Compatible with breastfeeding
Not absorbed through GI tract

Sulfonamides
Pregnancy Category C
Readily cross the placenta
Concerns of use at term

Lactation
Excreted into breastmilk in low levels
Use should be avoided in premature infants

Antifungals/Echinocandins
(anidulofungin, caspofungin, micafungin)
Pregnancy Category C
No data with anidulofungin
No human data with caspofungin, single case at

UVA, animal data suggests risk

Lactation
No human data, but probably compatible

Tetracyclines
(doxycycline, minocycline, tetracycline)
Pregnancy Category D
Can cause problems with teeth and bone and
other defects/effects
Have been linked to maternal liver toxicity

Lactation
Compatible with breastfeeding
Serum levels in infants undetectable