Obstetrics and Gynecology/Teratology and Associated Outcomes

Introduction to Teratology

Two to three per cent of all live births are complicated by malformation. The majority of these complications are due to unknown factors. The vast majority of recognized etiologies are genetic, with only 10% being attributed to environmental etiologies such as maternal health, infection, and teratogenesis.

A teratogen is a compound which permanently deforms the function or structure of a developing fetus in utero. In general, the degree of teratogenicity depends on

• Potency of the drug as a mutagen
• The susceptibility of the fetus to teratogenesis
• The dose of the teratogen
• The duration of teratogen exposure
• The degree of transfer from maternal to fetal circulation
• The time during gestation at which teratogen exposure occurred.
  • In general, the central nervous system, ears, eyes and limbs (from earlier to later, in that order) are the most affected.

Drug Classification for Pregnant Females

A (i.e. Always use): randomized controlled studies show no, or very rare risk of teratogenicity.

B (i.e. you're Better off using it): animal studies show no risk, or they do show risk in context of no risk shown in human studies.

C (i.e. we Can't say): no studies performed, animal findings in context of no human studies.

D (i.e. Don't use unless you have to): there are studies demonstrating fetal risk, but only use if you have to.

X (NEVER USE in pregnancy): there are proven fetal risks that outweigh any benefits of drug for the mother.

=== Recognized Teratogens and Teratogenic Disorders

Tobacco Consumption

Smoking is most likely to cause growth retardation, but has also been implicated in prelabour rupture of the membranes, preterm labour, abruption of the placenta, spontaneous abortion, perinatal morbidity and mortality, sudden infant death syndrome.

Smoking likely exerts its effects through competitive binding of carbon monoxide with hemoglobin, and peripheral vasoconstriction leading to fetal hypoxia.

Fetal Alcohol Spectrum

Epidemiology

• Occurs in 1% of all births

Etiology

• Alcohol ingestion: it is not clear if there is any safe amount of alcohol consumption in pregnancy.

Clinical Presentation

• Growth <10th percentile
• Facial anomalies: flattened upper lip, thin upper lip, small palpebral fissures, epicanthal folds, flattened nasal bridge, short nose
• CNS anomalies: microcephaly, mental retardation, learning disabilities

Cocaine

Cocaine generally produces growth restriction, preterm delivery, microcephaly, spontaneous abortion, placental abruption, limb anomalies, central nervous system abnormalities.

Cocaine likely exerts its effects through peripheral vasoconstriction leading to fetal hypoxia.

Warfarin

Women with indications for warfarin therapy should either abstain from pregnancy or switch to low molecular weight heparins.

Warfarin typically produces mental retardation, growth restriction, nasal hypoplasia, and ophthalmic abnormalities.

Angiotensin Converting Enzyme Inhibitors

ACE inhibitors will cause fetal renal failure and oligohydramnios which lead to pulmonary hypoplasia and limb contracture. Fetal cranial bone abnormalities are also common.

Isotretinoin (Accutane)

Isotretinoin used to treat acne may cause cardiac, otological, thymic, and central nervous abnormalities. In one quarter of cases, it causes mental retardation alone.