The defect must be completely characterized The agent

기형유발물질의 확인 ① The defect must be completely characterized. ② The agent must cross the placenta. ③ Exposure must occur during a critical developmental period. ④ There must be a biologically plausible association. ⑤ Epidemiological findings must be consistent. ⑥ The suspected teratogen causes a defect in an animal.

Criteria for proof of human teratogenicity ① Careful delineation of clinical cases ② Rare environmental exposure associated with rare defect, with at least three reported cases—easiest if defect is severe ③ Proof that the agent acts on the embryo or fetus, directly or indirectly ④ Proven exposure to agent at critical time(s) in prenatal development ⑤ The association must be biologically plausible ⑥ Consistent findings by two or more epidemiological studies of high quality: (a) Control of confounding factors (b) Sufficient numbers (c) Exclusion of positive and negative bias factors (d) Prospective studies, if possible (e) Relative risk of three or more ⑦ Teratogenicity in experimental animals, especially primates

Exposure during a critical developmental period. ① Preimplantation period Fertilization ~ 2 weeks “all or none period” ② Embryonic period. GA 4 ~ 10 weeks, organogenesis “critical developmental period” ③ Fetal period. GA 10 weeks ~ ex, brain

Table 14 -3. Food and Drug Administration Categories for Drugs and Medications Category A: Studies in pregnant women have not shown an increased risk for fetal abnormalities if administered during the first (second, third, or all) trimester(s) of pregnancy, and the possibility of fetal harm appears remote. Fewer than 1 percent of all medications are in this category. Examples include levothyroxine, potassium supplementation, and prenatal vitamins, when taken at recommended doses. Category B: Animal reproduction studies have been performed and have revealed no evidence of impaired fertility or harm to the fetus. Prescribing information should specify kind of animal and how dose compares with human dose. or Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus during the first trimester of pregnancy, and there is no evidence of a risk in later trimesters. Examples include many antibiotics, such as penicillins, macrolides, and most cephalosporins. Category C: Animal reproduction studies have shown that this medication is teratogenic (or embryocidal or has other adverse effect), and there are no adequate and well-controlled studies in pregnant women. Prescribing information should specify kind of animal and how dose compares with human dose. or There are no animal reproduction studies and no adequate and well-controlled studies in humans. Approximately two thirds of all medications are in this category. It contains medications commonly used to treat potentially life-threatening medical conditions, such as albuterol for asthma, zidovudine and lamivudine for human immunodeficiency viral infection, and many antihypertensives, including -blockers and calcium-channel blockers. Category D: This medication cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy or if a woman becomes pregnant while taking this medication, she should be apprised of the potential hazard to the fetus. This category also contains medications used to treat potentially life-threatening medical conditions, for example: systemic corticosteroids, azathioprine, phenytoin, carbamazepine, valproic acid, and lithium. Category X: This medication is contraindicated in women who are or may become pregnant. It may cause fetal harm. If this drug is used during pregnancy or if a woman becomes pregnant while taking this medication, she should be apprised of the potential hazard to the fetus. There a few medications in this category that have never been shown to cause fetal harm but should be avoided nonetheless such as the rubella vaccine.

Selected Drugs or Substances Suspected or Proven to Be Human Teratogens Alcohol Methyl mercury Angiotensin-converting enzyme inhibitors and Methotrexate angiotensin-receptor blockers Misoprostol Aminopterin Mycophenolate Androgens Paroxetine Bexarotene Penicillamine Bosentan Phenobarbital Carbamazepine Phenytoin Chloramphenicol Radioactive iodine Chlorbiphenyls Ribavirin Cocaine Streptomycin Corticosteroids Tamoxifen Cyclophosphamide Tetracycline Danazol Thalidomide Diethylstilbestrol (DES) Tobacco Efavirenz Toluene Etretinate Tretinoin Isotretinoin Valproate Leflunomide Warfarin Lithium Methimazole

Counseling for teratogen exposure women given negative information —such as a 1 - to 3 percent chance of having a malformed newborn—are more likely to perceive an exaggerated risk than women given positive information, that is, the 97 - to 99 -percent chance of having a child without a malformation. With a few notable exceptions, most commonly prescribed drugs and medications can be used with relative safety during pregnancy. For the few drugs believed to be teratogenic, counseling should emphasize relative risk. The concept of risk versus benefit also should be introduced.

약물과 태아기형 Alcohol-fetal alcohol syndrome

Fetal Alcohol Syndrome and Alcohol-Related Birth Defects Fetal Alcohol Syndrome Diagnostic Criteria—all required I. Dysmorphic facial features a. Small palpebral fissures b. Thin vermilion border c. Smooth philtrum II. Prenatal and/or postnatal growth impairment III. Central nervous system abnormalities a. Structural: Head size < 10 th percentile, significant brain abnormality on imaging b. Neurological c. Functional: Global cognitive or intellectual deficits, functional deficits in at least three domains Alcohol-Related Birth Defects I. Cardiac: atrial or ventricular septal defect, aberrant great vessels, conotruncal heart defects II. Skeletal: radioulnar synostosis, vertebral segmentation defects, joint contractures, scoliosis III. Renal: aplastic or hypoplastic kidneys, dysplastic kidneys, horseshoe kidney, ureteral duplication IV. Eyes: strabismus, ptosis, retinal vascular abnormalities, optic nerve hypoplasia V. Ears: conductive or neurosensory hearing loss VI. Minor: hypoplastic nails, clinodactyly, pectus carinatum or excavatum, camptodactyly, "hockey stick" palmar creases, refractive errors, "railroad track" ears

약물과 태아기형 Anticonvulsant-fetal hydantoin syndrome

약물과 태아기형 Vitamin A –Isotretinoin embryopathy

약물과 태아기형 Warfarin embryopathy

Herb and Common Name Relevant Pharmacological Effects Perioperative Concerns Echinacea: purple coneflower root Activation of cell-mediated immunity Allergic reactions; decreased effectiveness of immunosuppressants; potential for immunosuppression with long-term use Ephedra: ma huang Tachycardia and hypertension through Hypertension, arrhythmias with myocardial direct and indirect sympathomimetic ischemia and stroke; long-term use effects depletes endogenous catecholamines; lifethreatening interaction with monoamine oxidase inhibitors Garlic: ajo Inhibition of platelet aggregation; increased fibrinolysis; equivocal antihypertensive activity Increased risk of bleeding, especially when combined with other medications that inhibit platelet aggregation Ginger COX inhibitor Increased risk of bleeding Ginseng Lowers blood glucose; inhibition of Hypoglycemia; increased risk of bleeding; platelet aggregation; increased PT and decreased anticoagulation effect of warfarin a. PTT in animals Glucosamine and chondroitin Worsening of diabetes Kava: awa, intoxicating pepper, kawa Sedation, anxiolysis Increased sedative effect of anesthetics; effects of tolerance and withdrawal unknown St. John wort: amber, goat weed, hardhay, hypericum, klamatheweed Inhibition of neurotransmitter reuptake, monoamine oxidase inhibition unlikely Induction of cytochrome P 450 affecting cyclosporine, warfarin, steroids, protease inhibitors, and possibly benzodiazepines, calcium-channel blockers, and many other drugs Valerian: all heal, garden heliotrope, vandal root Sedation Increased sedative effect of anesthetics; liver damage; benzodiazepine-like acute withdrawal; potential to increase anesthetic requirements with long-term use Yohimbe Hypertension, arrhythmias

방사선량 측정 ① Type of study ② Type and age of equipment ③ Distance of target organ from radiation source ④ Thickness of the body part penetrated ⑤ Method or technique used for the study.

Table 41 -7. Radiopharmaceuticals Used in Nuclear Medicine Studies Study Estimated Activity Administered per Examination in Millicuries (m. Ci) Weeks' Gestationa Dose to Uterus/Embryo per Pharmaceutical (m. Sv)b Brain Hepatobiliary Bone Pulmonary Perfusion 20 m. Ci 99 m. Tc DTPA 5 m. Ci 99 m. Tc sulfur colloid 5 m. Ci 99 m. Tc HIDA 20 m. Ci 99 m. Tc phosphate 3 m. Ci 99 m. Tc-macroaggregated albumin 10 m. Ci 133 Xe gas 20 m. Ci 99 m. Tc DTPA 3 m. Ci 67 Ga citrate 20 m. Ci 99 m. Tc-labeled red blood cells 3 m. Ci 210 Tl chloride 5 m. Ci 99 m. Tc. O 4 0. 3 m. Ci 123 I (whole body) 0. 1 m. Ci 131 Id Whole body Thyroid-fetal 5 m. Ci 99 m. Tc sulfur colloid (1– 3 m. Ci) <12 12 12 <12 Any 8. 8 7 c 0. 45 1. 5 4. 6 0. 45– 0. 57 <12 <12 (combined) 8. 8 7. 5 5 <12 12 24 36 <8 1. 5– 6 2– 6 7– 9 12– 13 20 11 12– 13 20 11 6. 4 5. 2 3 2. 4 0. 10 0. 15 0. 88 1. 6 3 720 1300 5900 5 Ventilation Renal Abscess or tumor Cardiovascular Thyroid Sentinel lymphoscintigram a. To convert to mrad multiply x 100. b. Exposures are generally greater prior to 12 weeks compared with increasing gestational ages. c. Some measurements account for placental transfer. d. The uptake and exposure of 131 I increases with gestational age. DPTA = diethylenetriaminepentaacetic acid; Ga = gallium; HIDA = hepatobiliary iminodiacetic acid; I = iodine; m. Ci = millicurie; m. Sv = millisievert; Tc = technetium; Tc. O 4 = pertechnetate; Tl = thallium.

임신 중 영상진단의 가이드라인 ① Women should be counseled that x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects. Specifically, exposure to less than 5 rads has not been associated with an increase in fetal anomalies or pregnancy loss. ② Concern about possible effects of high-dose ionizing radiation exposure should not prevent medically indicated diagnostic X-ray procedures from being performed on a pregnant woman. During pregnancy, other imaging procedures not associated with ionizing radiation (e. g. , ultrasonography, MRI) should be considered instead of x-rays when appropriate. ③ Ultrasonography and MRI are not associated with known adverse fetal effects. ④ Consultation with an expert in dosimetry calculation may be helpful in calculating estimated fetal dose when multiple diagnostic x-rays are performed on a pregnant patient. ⑤ The use of radioactive isotopes of iodine is contraindicated for therapeutic use during pregnancy. ⑥ Radiopaque and paramagnetic contrast agents are unlikely to cause harm and may be of diagnostic benefit, but these agents should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.