Teratogenic drugs, fetal effects

Fetal Alcohol Syndrome

• pre and post-natal growth deficiency

• developmental delay/mental retardation

• hyperactivity/poor attention span

• microcephaly

• eye abnormalities (short palpebral fissures, epicanthal folds, microphthalmia, ptosis)

• midface hypoplasia (low nasal bridge, long flat philtrum, thin vermilion border)

• cardiac lesions (ASD, VSD)

• bone and joint abnormalities

Cocaine

• Effects on pregnancy: prematurity, abruptio placenta, spontaneous abortion, intrauterine growth retardation, microcephaly

• Teratogenic effects (secondary to fetal vascular disruption): urinary tract abnormalities, limb reduction defects, CNS defects, intestinal atresias

• Neurobehavioral effects:

  • neonatal abstinence syndrome: lethargy, poor responsiveness, hypertonicity, tremulousness, disorganized sleep and feeding patterns - EEG abnormalities

  • increased SIDS risk

Heroin

• withdrawal symptoms often begin shortly after birth; peak at 3-4 days; persist for 2-3 weeks; subacute form for 4-6 months.

• symptoms

  • CNS: jitteriness, high-pitched cry, sleep disturbances, hypertonia, seizures

  • metabolic: sweating, fever, sneezing, changes in respiration

  • GI: disturbances of sucking and feeding, vomiting, diarrhea

Marijuana: neonatal abstinence, fetal growth retardation

Tobacco: growth retardation; increased incidence of placenta previa and abruptio placenta

Phenytoin:

• fetal hydantoin syndrome features include growth deficiency, mental deficiency, nail hypoplasia, and craniofacial abnormalities (wide anterior fontanelle, ocular hypertelorism, broad/depressed nasal bridge)

• neonatal hemorrhage which can involve skin, liver, GI tract, brain

Carbamazepine: similar to fetal hydantoin syndrome

Valproic acid: craniofacial abnormalities, spina bifida, congenital heart disease

ACE inhibitors (captopril and enalapril, especially during 2nd and 3rd trimesters): growth retardation, rare skull ossification defects, neonatal acute renal failure

Warfarin:

• fetal warfarin syndrome features include midface hypoplasia, ear and skull abnormalities, CNS malformation, and mental retardation

• neonatal hemorrhage

• may have stippling of uncalcified epiphyses which disappears after first year of life

Magnesium Sulfate: respiratory and neuromuscular depression

Diethylstilbesterol: clear cell adenocarcinoma of the vagina in the offspring of women treated with this agent
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References: Behrman RE, Kliegman RM, Jenson HB. Nelson Textbook of Pediatrics 16th ed. WB Saunders, Philadeplphia 2000.