Teratogens + Congenital anomalies +neonatal pharmacology Flashcards
Teratogen definition
agent that can produce a permanent alteration of structure/function in an organism after exposure during embryonic/fetal life
No absolute teratogens- display effects under certain circumstances
Almost any agent toxic to mom can damage embryo
Factors affecting teratogenicity
Nature of the agent Dose - for most agents, only in presence of maternal toxicity Route Gestational timing Concurrent exposures Genetic susceptibility
Methylene blue considerations
given orally/iv for methemoglobinemia
given by intra-amniotic injection to assess PROM and in twin amniocentesis
Near term: hemolytic anemia, jaundice in newborn after intramniotic injection
16 weeks: multiple intestinal atresia in fetus after intramniotic injection
Critical period
usually has occurred before mom knows they’re pregnant
Greatest susceptibility of 0-8 weeks embryonic age
0-2 wks: relative insusceptibility - all or none, can repair or won’t implant
CNS susceptibility continues throughout pregnancy
Chorionic villi sampling - limb reduction defects
Exposure after limb formation
Transverse terminal LRDs increased, esp distal digital defects
Risk greater and defects more severe with earlier CVS
Vascular disruption?
similar effect with misoprostil
similar effect with cocaine, other v/c agents
Maternal diabetes teratogenicity
Heart defects (2-3%)
neural tube defects (1-2%; spina bifida, anencephaly)
proximal femoral hypoplasia
holoprosenencephaly
Maternal obesity embryonic risk
neural tube defects
Maternal antibodies risk to fetus
Rh disease: hydrops, death, severe anemia
Antiplatelet antibodies: proencephaly
Autoimmune endocrinopathies
SLE –> heart block, chondrodysplasia punctata
Birth defects due to teratogens
1-2% maternal metabolic disease
~1% maternal antibodies
2-3% infections
Infectious agents that can be teratogenic
Syphilis Toxoplasmosis Rubella CMV Varicella HIV Parvo LCMV
Teratogenic physical agents
Radiation: large doses, not X-rays
radioactive iodine after 13 weeks gestation can destroy fetal thyroid gland
CVS
Early amniocentesis (
Environmental toxins (teratogenic)
limited by dose and maternal toxicity
Methyl mercury
- ingestion of toxic amounts in food
- Minamata disease: cerebral palsy, intellectual disability, blindness, microcephaly
PCBs:
- rice oil disease: fetal growth retardation, “cola-coloured” parchment-like skin
- features resolve with time
- maternal ingestion of toxic amounts in food
Drugs of abuse -teratogenic
ALCOHOL: FASD, full form from severe chronic alcoholics
Cigarettes: v/c, small babies, miscarriage
Cocaine: vascular disruption
Toluene by inhalation
Medications that can be teratogenic
Thalidomide cytotoxic agents androgenic hormones DES valproic acids phenytoin phenobarbital trimethadione carbamazepine primidone accutane lithium warfarin misoprostol fluconazole trimethoprim ACEi ATII inhibitors
Anomaly definition
any abnormal deviation from expected in structure, form, or function
does not imply a specific cause
Etiology of congenital abnoramlities
2-3% at time of birth
3-5% at one year of life (+ internal anomalies not obvious at birth, like congenital heart defects)
Etiologic heterogeneity
cause cannot be determined by appearance alone
Important to determine whether isolated/part of a more generalized pattern
- isolated: often multifactorial
- generalized: usually not multifactorial
Minor anomalies
14% newborns
includes ear tag/pit, single palmar crease, D5 clinodactyly
usually of no functional significance
may be characteristics of certain patterns of anomalies e.g. Down syndrome
more likely to have major congenital anomaly if there are multiple minor ones
Types of congenital anomalies
malformation
disruption
deformation
Malformation anomalies
primary error of normal development/morphogenesis of an organ or tissue
may have a variety of causes
abnormal development from early in embryogenesis
Malformation examples
syndactyly
most spina bifida
most cleft palate
most congenital heart lesions
Disruption anomalies
morphologic defects resulting from a breakdown, or interference with, an originally normal developmental process
sometimes called secondary malformation
may result from extrinsic factor, like infection or trauma
not usually caused by single gene or chromosomal abnormality
may occur at any time during gestation
Examples of disruptions
amniotic band disruption
Porencephaly
Amniotic band disruption
amnion ruptured –> filmy strands may constrict arm –> amputation
usually sporadic
Porencephaly
due to infection/bleed?
disruption of previously normal brain tissue
large cyst in brain
