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Genetics Principles

Teratology

5 topics

Overview

Teratology is the study of agents (drugs, infections, maternal metabolic disturbances, physical exposures) that disrupt normal embryologic development. Where the Embryology chapter covers what's supposed to happen, this chapter covers what goes wrong when an external agent intervenes during a critical window. Two ideas anchor everything: timing matters (the all-or-none period vs. organogenesis vs. fetal period each have characteristic injury patterns) and mechanism matters (folate antagonism, vascular disruption, receptor binding, and methylation each give a recognizable phenotype).

Most exposed pregnancies still produce healthy infants, even for well-established teratogens; risk is relative, not absolute. The counseling task is to translate "exposure on day X at dose Y" into an evidence-based recurrence figure and a tailored surveillance plan.

Agents

The remaining leaves group teratogens by category: medications, alcohol/FASD, infectious (TORCH+), and maternal metabolic. Recreational substances and physical agents (radiation, hyperthermia) are covered briefly inside the maternal-metabolic and principles leaves.

Fetal Alcohol Spectrum Disorder (FASD)

Infectious Teratogens (TORCH+)

Maternal Metabolic & Environmental Teratogens

Medication Teratogens

Principles

The principles leaf below covers Wilson's rules, dose-response, critical windows, and the conceptual tools that apply across every agent.

Wilson's Rules & Teratogen Principles

Counseling Principles (cross-cutting)

  • Document exposure thoroughly: agent, dose, gestational timing, duration, maternal co-factors. Use MotherToBaby (OTIS), TERIS, or ReproTox for evidence-based exposure summaries.
  • Match surveillance to mechanism. A neural-tube-affecting exposure → targeted ultrasound + amniotic-fluid AFP. A cardiac teratogen → fetal echocardiography around 18–22 weeks.
  • Reframe risk. Background birth-defect rate is ~3% in the general population. A teratogenic exposure usually adds a defined increment, not 100% risk. "Your baby will probably be fine, and here's how we'll watch for the specific things that can go wrong."
  • Preconception is the high-leverage moment, especially for chronic medications (valproate switch, isotretinoin iPLEDGE, warfarin → LMWH planning). Once the patient knows she's pregnant, the critical window for many agents is already partly closed.
  • Paternal exposures (chemo, radiation) historically considered low-risk for teratogenesis, though there's accumulating evidence for modest effects on gametogenesis (DNA damage, epigenetic). Rarely the dominant clinical concern.

Clinical Pearls (cross-cutting)

  • Organogenesis = weeks 3–8 post-conception. Most structural teratogens strike here.
  • All-or-none period (weeks 0–2): exposure causes embryonic loss or full recovery, never malformation. Reassuring for very-early exposures.
  • Alcohol has no safe amount, no safe trimester, and is the single most common preventable cause of intellectual disability.
  • Valproate is uniquely problematic: neural tube defects, facial dysmorphism, autism, IQ reduction. Switch antiepileptic preconceptionally when possible.
  • Isotretinoin embryopathy drove creation of the iPLEDGE program. Severe craniofacial, cardiac, and CNS defects.
  • Warfarin embryopathy (weeks 6–9 highest risk): nasal hypoplasia, stippled epiphyses, CNS abnormalities. LMWH is safer in pregnancy because it doesn't cross the placenta.
  • TORCH+ is a useful starting list (Toxoplasmosis, Other, Rubella, CMV, Herpes) but parvovirus B19, Zika, syphilis, and varicella deserve separate consideration.
  • Maternal diabetes (especially poorly controlled, HbA1c >7%) is a teratogen; sacral agenesis (caudal regression) is the near-pathognomonic finding; cardiac and neural tube defects are also increased.
  • Maternal PKU unrecognized in pregnancy → microcephaly, IQ reduction, congenital heart defects from elevated phenylalanine. Restart phe-restricted diet preconceptionally.
  • Ionizing radiation has a threshold (~10–20 rad / 100–200 mGy) below which clinically detectable risk is minimal; diagnostic imaging almost never reaches this dose.

Resources

← Embryology