The first trimester of pregnancy is considered a sensitive period for the teratogenic effects of drugs. The fertilized egg 3 8 weeks is the embryonic stage, from the 4th week, the organs of the embryo begin to develop, and rapidly develop to the 3rd month. This period is the most active period of organ development, and it is also the period when drugs are most likely to interfere with the normal differentiation of embryonic tissue cells, which may lead to fetal miscarriage, malformation or organ function defects, and no drugs are used in this period as much as possible.
Classification criteria for harm to the fetus: In 1979, the U.S. Drug and Food Administration divided drugs into five categories: A, B, C, D, and X, based on animal experiments and clinical practice experience and adverse effects on the fetus. Class A is the safest;Class X is the most dangerous and contraindicated for pregnant women. Grade B is safe, grade C does not exclude risk, and grade D has evidence of risk, but the benefits of medication may outweigh the harms.
Category A: Animal experiments and clinical observations have not shown any damage to the fetus, and it is the safest category, such as penicillin sodium.
Category B: Animal experiments have shown that it is harmful to fetuses, but clinical studies have not confirmed it, or animal experiments have not found teratogenic effects, but there is no clinical verification data. A variety of commonly used clinical drugs belong to this category, such as erythromycin, sulfonamides, digoxin, chlorpheniramine, etc.
Category C: It has only been confirmed in animal experiments to have teratogenic or embryocidal effects on fetuses, but there is a lack of research data in humans. Such as gentamicin sulfate, chloramphenicol, promethazine hydrochloride, etc.
Category D: There is certain clinical data indicating that it is harmful to the fetus, but the efficacy of the disease of pregnant women is certain, and there is no alternative drug, and its benefits obviously exceed its harm, and then consider the application, such as anticonvulsant phenytoin, and streptomycin.
Class X: Drugs that are proven to be harmful to the fetus and are contraindicated during pregnancy.
The drugs that have been proven to have teratogenic effects in clinical practice are briefly described as follows:
Ethanol in the first trimester of pregnancy with a daily dosage of more than 2 g kg increases the incidence of congenital malformations by 2-3 times.
Anti-tumor drugs such as busulfan, chlorambucil, carmangis, chlorametha, cyclophosphamide, etc.;Methotrexate, fluorouracil, thiopurine, carcinolytic, etc.
Antibiotics penicillamine, tetracycline, chloramphenicol, etc.
Sex steroid hormones such as diethylstilbestrol, clomiphene, etc.
Others such as carbon monoxide, lithium preparations (lithium carbonate), mercury preparations (such as methylmercury, mercury sulfide);Retinoic acid, sodium valproate, trimethyldione, phenytoin, thalidomide (reaction arrest), and coumarins (e.g., warfarin).
Drugs that are harmful to the fetus.
Name of the drug, adverse effects.
Methotrexate, multiple malformations.
Cyclophosphamide, multiple malformations.
Chloramphenicol is associated with an increased risk of gray baby syndrome.
Chlorpropane, tolbutamide, neonatal hypoglycemia, and increased malformation rates.
Cortisone, the risk of cleft palate increases.
Barbiturates, diazepam, long-term drug use of neonates are dependent on drugs.
Tetracycline, impaired tooth and bone development.
Chloroquine, retinal damage.
Trimethyldione, bone deformity, microcephaly.
Lithium carbonate, cardiovascular malformations.
Ethanol can produce skull deformities, intellectual disability, and fetal alcohol syndrome.
Iodine, congenital goiter, hypothyroidism.
Long-term use of methadone, ** neonates are drug-dependent.
Methyltestosterone, virilization of the female fetus.
Anti-androgens, feminization of the male fetus.
Estryl, norethindrone, virilization of the female fetus.
Diethylstilbestrol, Müllerian duct dysplasia, adenocarcinoma, clear cell carcinoma of the cervix.
Phenytoin, cleft lip, cleft palate.
Tetracycline, tooth age, skeletal development disorders.
Propylthiouracil, congenital goiter.
Thalidomide, seal limb deformity.
Trimethyloxazoledione, congenital multiple malformations.
Dicoumarins, nasal deformities, eye damage, mental developmental disabilities, cardiac malformations, miscarriages, stillbirths, deafness.
Phencyclidine, infertility.
Isotretinoin, ear deformities, palatal deformities.
Tricyclic antidepressants, blood cell damage.
These drugs should be contraindicated in the first trimester. The information listed above is not exhaustive. Because those that are not included are not teratogenic, those that are included are not necessarily the most teratogenic. In addition, after the application of drugs with teratogenic properties, whether there is a malformation is related to the length of exposure of pregnant women to the drug, the size of the dose, and the gestational age. It is also associated with the risk of teratogenicity. In this case, valproate can cause an increase in the incidence of spina bifida and microcephaly in the fetus, but pregnant women exposed to sodium valproate still have about a 95% chance of getting a normal baby.