TERATOLOGY

&
CHRONIC POISONING
Prepared by:

Dr. Gehanath Baral

MBBS,DGO,MD
Senior Consultant Gynecologist & Obstetrician: Government of Nepal
Visiting Professor: CTGU
30th April, 2007

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Acute Poisoning in Pregnancy

• Priority to be given to mature adult than to the

unborn fetus:
• Conventional line of t/t irrespective of her
gestation
• Do not compromise the line of t/t of poisoning

• If no chance of survival of mother : CS delivery

of live fetus if decided by technical/consumer
team

2
 Chronic poisoning

1. Patient taking t/t for chronic illness

becomes pregnant

2. A course of drug taken for an acute

illness during the critical period

3. Abortifacient taken

4. Exposure to teratogens without

notice

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 Issues & Dilemma
1. Definite teratogenicity can not be predicted, i.e. All or none
phenomena does not apply during embryonic phase.

2. Anomaly scanning is not sensitive enough: both subjective &

objective errors occur

3. Non availability of adequate diagnostic/screening facilities.

4. Fetal protection from dying mother due to poisoning:

• Informed consent
• Medico legal factor
• Common consensus within technical team
• Feasibility

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 TERATOGENESIS

Defn. - Dysgenesis of fetal organs either in terms of

structural integrity or functional .

Teratogenic effect occurs :

1. During the period of organogenesis

2. Later alteration in structure or function of organ
system
3. IUGR / fetal death /carcinogenesis

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 TERATOGEN

• Is an infectious agent , drugs, chemical, or

irradiation that alters the morphology and
function of the fetus during a critical stage
of development .

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PHASES OF HUMAN DEVELOPMENT

1. RESISTENT PERIOD - Day 0 - 17 – all or

none phenomenon .

2. MAXIMUM SUSCEPTIBILITY PERIOD - 3 to 8

weeks – organogenesis .

3. LOWERED SUSCEPTIBILITY PERIOD - 9 –

38 Weeks – only functional derangement .

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ANOMALY AND TIME OF EXPOSURE

1. Anencephaly  Day 24

2. Limb reduction defect  Day 12 – 40

3. Transposition of great
vessels  Day 34

4. Cleft lip  Day 36

5. VSD  Day 42

6. Syndactyly  Day 42

7. Hypospadias  Day 84

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 Prescribing principles
1. All woman of reproductive age are at risk of pregnancy

2. Clear indication / benefit >risk

3. Avoid in 1st trimester if possible

4. Smallest effective dose / for the shortest period of time

5. Widely used drugs with good safety records than newer ones

6. Mol.wt.<1500D cross placenta but very few are teratogenic

7. Avoid polypharmacy / Encourage preconception counseling

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Until the thalidomide
disaster in the 1960's,
many people believed
that the placenta
formed a barrier
against potential
harmful drugs.

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 Food and Drug Administration (FDA)

Five categories :

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 trimesters.

B. Animal reproduction studies have shown confirmed

effect in controlled studies in women in the first trimester
and there is no evidence of a risk in later trimesters.

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C. Either studies in animals have revealed adverse effects
on the fetus and there are no controlled studies in
women, OR studies in women and animals are not
available.

D. There is positive evidence of human fetal risk, but the

benefits from use in pregnant women may be acceptable
despite the risk.

X. Studies in animals or human beings have demonstrated

fetal abnormalities.

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 Causative Agents

1. VIRAL INFECTIONS

2. NON VIRAL INFECTIONS

3. DRUGS:
– Medicinal
– Recreational

4. CHEMICAL AGENTS

5. IONIZING RADIATION

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1. VIRAL INFECTIONS

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RUBELLA (GERMAN MEASLES)

• Maternal infection during pregnancy may result in:

Triad of fetal cardiac defects :

1. Patent ductus arteriosus

2. Pulmonary artery stenosis
3. Atrioventricular ( AV ) septal defects

• Also causes - cataract, deafness,

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CYTOMEGALOVIRUS (CMV)

1. Microcephaly, chorioretinitis

2. Hepatosplenomegaly

3. Intracranial calcification

4. Mental retardation

5. Heart block

6. Petechiae

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HERPES VIRUS 2 ( HSV-2)

1. Transmission to fetus is uncommon

( <1 in 7500 cases )

2. Rarely causes fetal malformation

3. May cause fetal growth retardation ,

microcephaly , chorioretinitis ,
cerebral calcification

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VARICELLA ZOSTER VIRUS
( CHICKEN POX )

1. Transmitted in third
trimester in 24% of
cases .
2. Fetal skin scarring
3. Limb hypoplasia
4. Rudimentary digits
5. Club foot
6. Microcephaly
7. Mental retardation

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HUMAN IMMUNODEFECIENCY VIRUS
( HIV )

Can cause:

• Preterm deliveries.
• Low birth weight infants
• Growth retardation,
• Craniofacial abnormalities
• Microcephaly.
• Fetal infection.

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2. NON VIRAL INFECTIONS

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TOXOPLASMA GONDII

• Protozoan parasite – found in cats .

• Transplacental transmission

Causes –
1. Miscarriage
2. Perinatal death
3. Chorioretinitis
4. Microcephaly
5. Cerebral calcification

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 TREPONEMA PALLIDUM

• Spirochete causing syphilis .

• Transplacental transmission .

Causes –
1. Miscarriage
2. Perinatal death
3. Hepatosplenomegaly
4. Joint swelling
5. Skin rash , anemia , jaundice.
6. Metaphysial dystrophy , Hutchinson teeth .
• Antibiotic given to mother is adequate for the fetus also .

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3.1.1. CATEGORY X DRUGS

ABSOLUTE CONTRAINDICATION
IN
PREGNANCY

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 THALIDOMIDE

• Antinausea drug

Causes –

1. Meromelia , amelia
2. Ear and nasal abnormalities
3. Cardiac defects
4. Lung defects
5. Pyloric and duodenal stenosis
6. GIT atresia .

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AMINOPTERIN AND METHOTREXATE

• Folic acid antagonist

Causes –

1. Small stature
2. Abnormal cranial ossification
3. Ocular hypertelorism
4. Low set ears
5. Cleft palate

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Busulfan / Cyclophosphamide

• Alkylating agents

Causes –

1. Cleft palate
2. Eye defect
3. Hydronephrosis
4. Renal agenesis
5. Absence of toes
6. Growth retardation

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 PHENYTOIN

• Antiepileptic

Causes –

1. Fetal hydantoin syndrome –

growth and mental retardation
2. microcephaly
3. craniofacial defects
4. nail and digit hypoplasia .

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 TRIZOLAM

• Hypnotic drugs

Causes in first trimester –

1. Fetal cleft lip

2. Cleft palate .

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 WARFARIN

• Anticoagulant drug .

Causes –

1. Stippled epiphysis
2. Mental retardation
3. Microcephaly
4. Seizures
5. Fetal hemorrhage
6. Optic atrophy .

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 ISOTRETINION

• Retinoic acid derivative .

Causes ( Vitamin A Embryopathy ) –

1. Fetal CNS abnormalities

2. External ear abnormalities
3. Eye abnormalities
4. Facial dysmorphia

5. Cleft palate

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 CLOMIPHENE

• Nonsteroidal ovulatory stimulant .

• No established birth defects are

recorded , there have been report
of birth anomalies .

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DIETHYLSTILBESTEROL

• Synthetic estrogen

Exposure to DES in utero

causesreproductive system
disorders

1. Cervical hood
2. T-shaped uterus
3. Hypoplastic uterus
4. Ovulation disorders
5. Cervical incompetence
6. Increased risk of
adenocarcinoma of vagina.

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 ETHISTERONE ,
NORETHISTERONE,
MEGESTEROL

• Synthetic progesterone
derivative

Causes –

1. Masculinization of genitalia in
female embryo
2. Hypospadiasis in male embryo
3. Cardiovascular abnormalities .

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OVCON , LEVELEN AND NORINYL

• Oral contraceptives
Causes –
• Fetal abnormalities
• VACTERL Syndrome :
1. Vertebral
2. Anal
3. Cardiac
4. Tracheoesophageal
5. Renal
6. Limb malformation

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 NICOTINE

• Poisonous addictive alkaloid

• Delivered by cigarette smoking

Causes –

1. Intrauterine growth retardation

2. Premature delivery
3. Low birth weight
4. Fetal hypoxia

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 ALCOHOL

• Organic compound , >140gms/ week .

Causes –

1. Fetal alcohol syndrome :

• Mental retardation ,
• Microcephaly ,
• Hypoprosencephaly ,
• Limb deformity ,
• Craniofacial abnormalities
• Cardiovascular defects .

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3.1.2. CATEGORY D DRUGS

DEFINITE EVIDENCE
OF RISK TO FETUS

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TETRACYCLINE / DOXYCYCLINE

• Antibiotics in tetracycline family .

Causes –

1. Permanently stained teeth

2. Hypoplasia of enamel in fetus

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STREPTOMYCIN / AMIKACIN /
TOBRAMYCIN

• Antibiotics of aminoglycoside family

Causes –

1. Fetal cranial nerve VIII toxicity

2. Permanent bilateral deafness
3. Loss of vestibular function .

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PHENOBARBITOL / PENTOBARBITO L

• Barbiturates

Causes –

1. High incidence of fetal abnormality .

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DIAZEPAM / CHLODIAZEPOXIDE/
ALPRAZOLAM

• Anticonvulsant and antianxiety

Causes –

1. Cleft lip and cleft palate

especially in first trimester.

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 LITHIUM

• For manic depressive disorder .

Causes –

1. Fetal cardiac defects ( Ebstein

anomaly and malformation of
great vessels )

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CHOLROTHIAZIDE

• Diuretic and antihypertensive

Causes –

1. Fetal jaundice

2. Thrombocytopenia

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Commonly used antimicrobials

• B - Amphotericine, Azithromycine,
Cephalosporins, Didanocin,
Erythromycine, Metronidazole,
Nitrofurantoin, Nystatin, Penicillins,
Sulphonamides

• C – Acyclovir, Chloroquin, Fluconazole,

Fluoroquinolone, Gancyclovir, Imipenem,
Itraconazole, Mebendazole, Pyrantel,
Stavudin, Trimethoprim, Vancomycine,
Zacitabine, Zidovudine

• C/D - Aminoglycocides

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Commonly used CVS drugs

• B – Heparin(Low mol.wt.), Urokinase

• B/C – Local anesthetic antiarrhythmics

• C – Adenosine,Beta blockers, Bretylium,

Calcium antagonists, Digoxin,
Disopyramide, Frusemide,
Heparin(Conventional ), Methyldopa,
Quinidine, Streptokinase

• C/D – ACE inhibitors

• D – Amioderone, Coumarins, Thiazides

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Commonly used drugs in Psychiatric
disorders

• B – Fluoxetin, Bupropion, Clozapine

• C – Doxepin, Phenelzine,
Chlorpropamide, Thioridazine,
Trifluperazine, Haloperidol, Clonazepam,
Lorazepam,Oxazepam

• D – Amitryptyline, Clomipramine,
Imipramine, Nortriptyline, Alprazolam,
Diazepam, Chlordiazepoxide

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 3.2 Recreational drugs

1. Lysergic acid diethylamine ( LSD ) ,

Marijuana , Caffeine – not teratogenic .

2. Cocaine – increase risk of various

congenital anomalies , still births, Low
birth weight , placental abruption .

3. Heroin – Severe neonatal withdrawal .

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4. CHEMICAL AGENTS

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ORGANIC MERCURY

CAUSES –

1. Fetal neurologic damage

2. Seizures
3. Psychomotor retardation
4. Cerebral palsy
5. Blindness
6. Deafness .

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 LEAD

Causes –

1. Growth retardation
2. Increased perinatal mortality
3. Developmental delay

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 5. IONIZING RADIATION

1. Acute high dose radiation ( > 250 rads ) –

fetal microcephaly , mental retardation ,
leukemia .

2. Diagnostic radiation – not significant dose

to cause fetal abnormality .

3. Radioactive cocktail iodine should not be

given after 10 weeks – impaired fetal
thyroid development

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 Conclusion

1. We can talk hours and days but still lag

behind protecting fetus and maternity.

2. We speak statistical language of getting

affected in terms of ratio and percentage,
but still do not know about the particular
patient.

3. Under the shield of BENEFIT-

OUTWEIGHS THE POTENTIAL RISK
we are still practicing polypharmacy.

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 Finally Everyone Says

Pardon me god! With the best of

my knowledge I am practicing
medicine.

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Cleft palate

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