Obstetric Topic 42. Genetic counseling - Teratology

I. Teratology

Teratology: study of congenital abnormalities and agents that disturb embryonic/fetal development.
Teratogen: chemical, physical or biological factor causing structural, functional, growth or neurodevelopmental defect.
Counseling after exposure estimates risk by agent, timing and dose; fetal damage is not automatic.

Timing of exposure is the most important determinant.
Dose, duration, route, placental transfer and maternal metabolism.
Fetal genetic susceptibility and combined exposures, e.g. alcohol + smoking + poor nutrition.

Preimplantation / first ~20 days after fertilization: "all-or-none" effect → embryonic death or no permanent defect.
Organogenesis (about days 20-56 after fertilization; 5-10 gestational weeks): highest risk of major structural malformations.
2nd-3rd trimester: growth, CNS development and organ function can still be impaired.
CNS remains vulnerable throughout pregnancy.

Poor periconceptional glycemic control → ↑ congenital anomaly risk.
Typical defects: cardiac anomalies, neural tube defects, caudal regression/sacral agenesis, renal/skeletal anomalies.
Prevention: optimize HbA1c before conception; folic acid; detailed US and fetal echocardiography if indicated.

High maternal phenylalanine is teratogenic even if fetus is only a carrier.
Fetal effects: microcephaly, intellectual disability, congenital heart disease, growth restriction.
Prevention: strict low-phenylalanine diet before conception and throughout pregnancy.

Uncontrolled Graves disease: fetal/neonatal thyrotoxicosis, growth restriction, prematurity, stillbirth.
Severe hypoxia, renal disease, HT/preeclampsia and autoimmune disease mainly cause placental insufficiency/FGR.

No known safe amount or safe timing in pregnancy.
Fetal alcohol spectrum disorders: growth restriction, CNS/neurobehavioral impairment and facial dysmorphism.
Classic signs: short palpebral fissures, smooth philtrum, thin upper lip, microcephaly, intellectual disability, cardiac defects.

Nicotine + carbon monoxide → vasoconstriction and fetal hypoxia.
Risks: miscarriage, FGR/low birth weight, placenta previa, abruption, PPROM, preterm birth, stillbirth, SIDS.

Retinoids/isotretinoin: severe craniofacial, cardiac, CNS and thymic defects.
Valproate/antiepileptics: neural tube defects and neurodevelopmental risk → optimize regimen before conception.
Warfarin: embryopathy and fetal bleeding/CNS defects → LMWH preferred when anticoagulation is needed.
ACE inhibitors/ARBs: fetal renal injury, oligohydramnios, skull hypoplasia, neonatal renal failure.
Methotrexate: abortion, growth restriction, craniofacial/skeletal defects.
Tetracyclines after midpregnancy: tooth discoloration and bone effects.
Radioactive iodine: fetal thyroid destruction; ionizing radiation risk depends on dose.

TORCH and related infections: toxoplasmosis, syphilis, rubella, CMV, HSV, VZV, parvovirus B19, Zika.
Hyperthermia/high fever in early pregnancy → neural tube defect risk.
Radiation: avoid unnecessary exposure; risk depends on dose and gestational age.

Identify high-risk women/couples and review medication before pregnancy.
Replace teratogenic drugs when possible; use contraception until high-risk medication is stopped or changed.
Optimize diabetes, PKU, thyroid disease, epilepsy, HT and autoimmune disease.
Folic acid before conception/early pregnancy; vaccinate before pregnancy when needed (rubella/MMR, varicella).
Avoid alcohol, tobacco/nicotine, illicit drugs and unnecessary radiation.

Clarify exposure: substance, amount, timing, duration and maternal illness.
Offer genetic/teratology counseling, targeted ultrasound, fetal echocardiography, MRI or diagnostic testing when indicated.
Termination is discussed only after individualized risk assessment, fetal findings, legal framework and parental decision.