وصف
A teratogen is an agent that can disturb the development of the embryo or Fetus. The clinical consequences of drug teratogens lead to developmental defects in humans. Defects may be due to genetic, environmental, or unknown causes. Drug use is an uncommon cause of birth defects, but certain medications can increase the risk of developing a birth defect.
Join the Case Based discussion with Dr Aruna Reddy Senior Gynecologist and Head OBG Department to have an exclusive learning on Teratology and drugs in Pregnancy.
ملخص
- Teratology is the study of developmental abnormalities in organisms. Medical genetics focuses on congenital abnormalities, dysmorphies, and developmental toxicities caused by environmental factors, including medications, radiation, and viruses. Teratogens are substances or organisms that cause birth defects, with examples including retinol, mercury, alcohol, lead, and benzodiazepines, which should be avoided during pregnancy.
- Clinical teratology studies the environmental contribution to prenatal growth abnormalities, morphological defects, and developmental issues in embryos. This field emerged after the rubella pandemic and the thalidomide effect. The susceptibility to teratogenic agents depends on genotypes of both mother and fetus, drug dosage, gestational age at exposure, and drug pharmacokinetics/pharmacodynamics. Identification methods include animal studies, epidemiological studies, and case-control surveillance.
- Understanding clinical teratology is essential because teratogen-induced birth defects are preventable by adjusting the dose-response relationship of drugs. Birth defects have a significant impact on healthcare systems and resources. FDA regulations for drug testing on animals were developed, requiring dosages high enough to cause maternal toxicity. Modern studies consider species-specific responses to drugs.
- Teratogen-induced birth defects account for 2-3% of cases, while maternal infections and chromosomal defects contribute similarly. Genetic factors contribute to about 20%, but the root cause remains unknown in 60-75% of cases. Basic principles of teratology include susceptibility depending on the conceptus genotype, variable phenotypes in exposed implants, and genetic sensitivity.
- Anti-epileptic drugs, when converted to reactive metabolites, cause DNA and protein damage, leading to alterations in cell division, migration, and transcription, ultimately resulting in teratogenesis. Susceptibility varies with developmental stage; pre-implantation exposure results in an all-or-none phenomenon, while organogenesis is a period of peak sensitivity.
- Teratogenic agents act specifically, initiating pathogenesis through reduced apoptosis, impaired morphogenetic movement, or mechanical disruption. The final manifestation can be death, malformation, growth retardation, or functional disorders, depending on the timing of exposure. Access to developing tissues depends on the agent's nature, maternal dose, and placental transfer. Manifestations are related to the agent's dosage, with regulators defining no-effect and threshold levels.
- Criteria associated with teratogenicity include clearly defined defects, the agent's ability to cross the placenta, exposure during a critical period, biologically plausible associations, and consistent epidemiological findings. High-quality epidemiological studies are crucial, and animal studies are necessary to prove the teratogenic effect before labeling a drug as such.
- The FDA classification system for drugs in pregnancy categorizes them into A, B, C, D, and X. Category A drugs have not shown increased risk in pregnant women. Category B drugs have shown no harm to the fetus in animal studies or have shown animal adverse effects but controlled studies on pregnant women have failed to show risk. Category C drugs show teratogenic effects in animal studies, but there are no adequate studies in pregnant women. Category D drugs can cause harmful effects to the pregnant woman. Category X drugs are contraindicated in pregnancy. In 2008, the FDA added fetal risk summaries and clinical considerations to replace the letter categories.
نموذج شهادة
حول المتحدثين
Dr Aruna Reddy
طبيبة أمراض النساء والتوليد ورئيسة قسم أمراض النساء والتوليد في مستشفى أومني كوكاتبالي، حيدر أباد
تعليقات
تعليقات
يجب عليك تسجيل الدخول لتتمكن من ترك تعليق.