A 32-year-old G2P0A1 woman presents at 36 weeks of gestation for the first time during her pregnancy. The patient has no complaints, currently. However, her past medical history reveals seizure disorder, which is under control with valproic acid and lithium. She has not seen her neurologist during the past 2 years, in the absence of any complaints. She also reports a previous history of elective abortion. The physical examination is insignificant. Her blood pressure is 130/75 mm Hg and pulse is 80/min. The patient is scheduled to undergo regular laboratory tests and abdominal ultrasound. Given her past medical history, which of the following conditions is her fetus most likely going to develop?

Intrauterine growth restriction

A 3-day-old female newborn delivered vaginally at 36 weeks to a 27-year-old woman has generalized convulsions lasting 3 minutes. Prior to the event, she was lethargic and had difficulty feeding. The infant has two healthy older siblings and the mother's immunizations are up-to-date. The infant appears icteric. The infant's weight and length are at the 5th percentile, and her head circumference is at the 99th percentile for gestational age. There are several purpura of the skin. Ocular examination shows posterior uveitis. Cranial ultrasonography shows ventricular dilatation, as well as hyperechoic foci within the cortex, basal ganglia, and periventricular region. Which of the following is the most likely diagnosis?

Congenital Toxoplasma gondii infection

Congenital parvovirus infection

Congenital Treponema pallidum infection

Congenital cytomegalovirus infection

A 26-year-old woman comes to the physician for evaluation of nausea and fatigue. Her last menstrual period was 8 weeks ago. She has a history of bipolar disorder controlled by a drug known to sometimes cause hypothyroidism and nephrogenic diabetes insipidus. She does not smoke cigarettes or drink alcohol. A urine pregnancy test is positive. An ultrasound of the pelvis shows a viable intrauterine pregnancy. The fetus is most likely at increased risk for which of the following anomalies?

Atrialization of the right ventricle

A 26-year-old G1P0 mother is in the delivery room in labor. Her unborn fetus is known to have a patent urachus. Which of the following abnormalities would you expect to observe in the infant?

Meconium discharge from umbilicus

A 24-year-old woman comes to the physician for preconceptional advice. She has been married for 2 years and would like to conceive within the next year. Menses occur at regular 30-day intervals and last 4 days with normal flow. She does not smoke or drink alcohol and follows a balanced diet. She takes no medications. She is 160 cm (5 ft 3 in) tall and weighs 55 kg (121 lb); BMI is 21.5 kg/m2. Physical examination, including pelvic examination, shows no abnormalities. She has adequate knowledge of the fertile days of her menstrual cycle. Which of the following is most appropriate recommendation for this patient at this time?

Begin high-dose vitamin A supplementation

Begin vitamin B12 supplementation

Teratogenic exposures — USMLE Lesson

Principles of Teratology - Toxic Timelines

Teratogen: Any agent causing fetal structural or functional abnormalities. Key principles include:
- Timing: Critical periods of susceptibility.
- Dose: Dose-response relationship.
- Genotype: Maternal & fetal genes modify risk.
- Specificity: Predictable pattern of anomalies.

⭐ The period of organogenesis (weeks 3-8) is the most critical, where exposure can cause major congenital malformations.

Pharmacological Phantoms - Pills & Problems

Teratogenic Exposure Outcomes by Gestational Stage

Drug Class	Specific Drug(s)	Key Congenital Defects
Immunomodulator	Thalidomide	Phocomelia (limb reduction defects), Amelia
Antiepileptics	Valproate	Neural tube defects (spina bifida), hypospadias
	Phenytoin	Fetal Hydantoin Syndrome: craniofacial anomalies, hypoplastic nails/phalanges
	Carbamazepine	Neural tube defects, craniofacial defects
Retinoids	Isotretinoin	CNS, craniofacial (microtia), cardiovascular defects
Antihypertensives	ACE Inhibitors/ARBs	Renal dysplasia, oligohydramnios, skull ossification defects
Anticoagulant	Warfarin	Fetal Warfarin Syndrome: Nasal hypoplasia, stippled epiphyses
Mood Stabilizer	Lithium	Ebstein's anomaly (atrialization of right ventricle)
Antimetabolite	Methotrexate	CNS (anencephaly, hydrocephalus) & limb abnormalities

Infections & Maternal Illness - Invading Pathogens

TORCH Infections
- Toxoplasmosis: Classic Tetrad → Chorioretinitis, Hydrocephalus, Intracranial calcifications, Convulsions.
- Other:
  - Syphilis: Hutchinson's triad (interstitial keratitis, notched incisors, 8th nerve deafness).
  - VZV: Limb hypoplasia, skin scars.
  - Parvovirus B19: Hydrops fetalis.
- Rubella: Classic Triad → PDA (or PPS), Cataracts, Sensorineural deafness.
- Cytomegalovirus (CMV): Periventricular calcifications, microcephaly, sensorineural hearing loss.
- Herpes Simplex (HSV-2): Skin vesicles, keratoconjunctivitis, meningoencephalitis.
Maternal Illness
- Diabetes (uncontrolled): Caudal regression syndrome, macrosomia, transposition of great arteries.
- Alcohol (Fetal Alcohol Syndrome): Smooth philtrum, thin vermilion border, small palpebral fissures.

⭐ CMV is the most common congenital viral infection worldwide.

Congenital Syphilis: Palmar/Solar Rash in Newborn

Radiation & Physical Agents - Environmental Exposures

Ionizing Radiation (>5-10 rads)
- <2 weeks: "All-or-none" effect (embryonic death or normal development).
- 3-8 weeks: Peak sensitivity. Leads to severe congenital anomalies, especially CNS.
- >8 weeks: Results in microcephaly, intellectual disability, and growth restriction.
Hyperthermia
- Maternal fever, hot tubs/saunas.
- Associated with ↑ risk of neural tube defects (NTDs) and cardiac defects.

⭐ The threshold for teratogenic effects from acute ionizing radiation exposure is generally considered to be >5 rads. Most diagnostic procedures deliver doses well below this level.

Fetal Radiation Exposure Effects by Gestational Age

ACE inhibitors are associated with renal dysplasia, oligohydramnios, and skull defects.

Valproate carries the highest teratogenic risk among antiepileptics, causing neural tube defects.

Lithium exposure is classically linked to Ebstein's anomaly of the tricuspid valve.

Warfarin use during pregnancy can lead to nasal hypoplasia and stippled epiphyses.

Isotretinoin (Vitamin A) is a potent teratogen causing severe craniofacial, cardiac, and CNS anomalies.

Fetal Alcohol Syndrome features include a smooth philtrum, thin upper lip, and short palpebral fissures.

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