Antepartal Care: Teratology

• Teratogens (birth defects) any agent or non-genetic factor that produces permanent abnormal embryonic physical development of physiology.
• Historical Events:
  • 1941: Rubella (blindness, Congenital Heart defects)
  • 1950’s: Methylmercury (neurotoxicity)
  • 1960’s: Thalidomide (phocomelia)
  • 1970’s: Alcohol (fetal alcohol syndrome)
• Principles of Teratology:
  • All or none phenomenon (from conception to implantation)-prenatal death
  • Dose dependency
  • Critical periods for certain effects
  • Duration of exposure
  • Host suseptibility
  • Drug interactions
    • BEST: Single drug; lowest dose
• Critical periods during human development:
• Embryonic 3-8weeks; Gestational age 5-10weeks
• 
• Effect of teratogen by (gestational) week exposure:
  • 1-6 weeks: CNS
  • 2-7 weeks: Heart
  • 3-8 weeks: Extremities
  • 3-8 weeks: Eyes
  • 5-8 weeks: Palate
  • 6-10 weeks: External Genitalia
• Thalidomide:
  • Introduced in 1956 as a seditive & anti-nausea agent
  • Withdrawn in 1961
  • Discovered to be human teratogen causing absence of limbs or limb malformations in newborns
  • 5000-7000 infants effected
  • Resulted in new drug testing rules
• Pre-Embryonic Stage:
  • Time of fertilization & up to implantation
  • First 2 weeks of gestation
  • Exposure to teratogens in this period may lead to improper implantation & spontaneous abortion, Also called “All or None”.
• Critical Period- Embryonic Period:
  • From day 14-18 to day 54-60 post-conception (this is the critical period)
  • Period of most extensive organ differentiation (the heart-first 38days; arms/legs-first 49days; teeth-first 56days, etc.)
  • Exposure to teratogens during this period can cause structural and functionatl birth defects.
• Fetal Period:
  • From day 56 of gestation to delivery
  • Differentiation of the palate, external genitalia, and ear are examples for this period. Structural defects as well as fetal growth retardation can occur.
• Known or strongly suspected Teratogens (Drugs & Chemicals)
  • Alcohol
  • Androgens (testosterone)
  • ACE Inhibitors (hypertensive medications)
  • Antithyroid medications
  • Coumadin
  • Carbamezepine, Phenytoin, Valproic Acid (cleft palate)
  • Folic Acid Antagonist (Hyper/Hypobilrubemia
  • Cocaine
  • Lead, Mercury+
  • Lithium (Bipolar meds. -cardiac defects)
  • NSAID’s
  • Tetracycline (discolor teeth/effect bone growth)
  • Thalidomide
  • NO Sulfa-drugs
• Known or Strongly Suspected Teratogens (INFECTIONS)
  • CMV-cytomet.virus
  • Rubella
  • Syphilis (Treat w/ PCN-not for babies/PCN desensitizes preg.women) baby bleeds to death
  • Toxoplasmosis
  • Varicella
• SSRI’s and Birth Defects (To treat depression)
  • Paxil, after 20th.wk, 1st trimester
    • Persistant Pulmonary Hypertension; taken after 20th wk; respiratory problems; 6 times greater risk
    • RR of atrial and ventricular septal defects w/ 1st trimester use; fetal echocardiography to screen in women exposed
  • Prozac, third trimester use
    • preterm delivery, respiratory difficulty, admission to NICU, jitteriness
  • JAMA, May 2008: SSRI’s-late in preg-3times greater risk-respiratory prob. in newborns (including Effexor)
  • FDA Category D
• FDA Categories:
  • A: Controlled studies in humans/ but not shown an increased risk for BD’s
  • B: Animal studies show negative for BD’s/no adequate human studies OR animal/human studies not available
  • C: Animal Studies show risk/ lack in human data
  • D: Human data-show risk (benefit may outweigh)
  • X: Animal/Human data positive
• Smoking in Pregnancy
  • Associated with reduced birth weight (IUGR & LBW), pematurity, stillborn, placental abruption
• Fetal Alcohol Syndrome (FAS)
  • First described in 1970s
  • Facial abnml, growth retardation, CNS effects, reduced intelligence
  • Facial effects: microcephaly, flat face, thin lips, missing groove above lip, short nose
  • Effects 4-12 thousand infants per year
  • Fetal Alcohol effects: (FAE) milder form but still CNS involvement