gynecology and obstetrics
Drug Safety in Pregnancy
Drug Transfer and Metabolism During Pregnancy
During pregnancy, medications are often required to treat certain disorders. In general, when potential benefit outweighs known risks, medications may be considered for treatment of disorders during pregnancy. Not all medications or other substances in the maternal circulation cross the placenta (transfer) to the fetus. Some drugs that cross the placenta may have a direct toxic effect or a teratogenic effect. Drugs that do not cross the placenta may still harm the fetus by Constricting placental vessels and thus impairing gas and nutrient exchange Producing severe uterine hypertonia that results in anoxic injury Altering maternal physiology (eg, causing hypotension) For a list of some medications with adverse effects during pregnancy, see table. Drugs diffuse across the placenta similarly to the way they cross other epithelial barriers (see Drug Absorption ). Whether and how quickly a drug crosses the placenta depend on the drug’s molecular weight, extent of its binding to another substance (eg, carrier protein), area available for exchange across the placental villi, and amount of drug metabolized by the placenta. Most drugs with a molecular weight of A drug’s effect on the fetus is determined largely by fetal age at exposure, placental permeability, maternal factors, drug potency, and drug dosage. Fetal age affects the type of drug effect: Before the 20th day after fertilization:Drugs given at this time typically have an all-or-nothing effect, killing the embryo or not affecting it at all. Teratogenesis is unlikely during this stage. Teratogenesis is most likely at this stage. Drugs reaching the embryo during this stage may result in Spontaneous Abortion , a sublethal gross anatomic defect (true teratogenic effect), covert embryopathy (a permanent subtle metabolic or functional defect that may manifest later in life), or an increased risk of After organogenesis (in the second and third trimesters):Teratogenesis is unlikely, but drugs may alter growth and function of normally formed fetal organs and tissues. As placental metabolism increases, doses must be higher for adverse fetal effects to occur. Maternal factors include those that affect drug Drug Absorption , The overall rate of major structural birth defects in the United States is approximately 3% ( References ); most malformations result from genetic, environmental, multifactorial, or unknown causes. It is difficult to determine the overall rate of congenital malformations caused by therapeutic drugs. As an example, in one study of 5504 cases of birth defects, only 20% had a definite cause and < 1% of cases with known causes were due to medications ( 