Medication

Therapeutic drug use may be necessary during normal pregnancy. Multiple factors, including gestational age and stage of development, dose and duration of exposure, and individual susceptibility, influence the potential effects of drug exposure during pregnancy. Teratogenesis is defined as the dysgenesis of fetal organs, as evidenced either structurally or functionally. Typical manifestations include restricted growth, fetal death, carcinogenesis, and malformations. 11 The fetus is most vulnerable to teratogenic effects at 4 to 12 weeks' gestation, the period of organogenesis. Exposure early in pregnancy may lead to spontaneous abortion. Exposure later in pregnancy is a less common problem but may also be teratogenic secondary to alterations in placental blood flow as well as direct potential fetal effects. Medication use during pregnancy may also have consequences in the neonate, such as central nervous system (CNS) depression, seizure, respiratory depression, kernicterus, or premature closure of the ductus arteriosus. Manifestations depend on the specific medication. Neonatal withdrawal may occur after maternal use of opiates or benzodiazepines during pregnancy. Finally, the adverse effects of fetal exposure to some medications (e.g., tetracyclines, which produce discoloration of teeth and bone, and diethylstilbestrol, which produces female genital tract abnormalities) may not be evident until later in the life of the child.

Pharmaceutical companies do not test drugs in pregnant women to determine potential fetal effects. Much of the available information on teratogenesis is based on animal studies, inadvertent human exposure during unrecognized pregnancies, and case reports or epidemiologic studies of pregnancy outcome after therapeutic drug administration. Exposure-related risk may be difficult to distinguish from spontaneous occurrence rates. Manufacturer labeling and drug reference books therefore often contain ambiguous statements concerning use of drugs in pregnancy. The US Food and Drug Administration (FDA) currently employs a system that classifies drugs in five risk categories based on available information ( T.aMe 99il). Because of ambiguity and potential inaccuracy within this system, alternative ways of outlining estimated fetal risk for both physicians and the general population are being investigated. 11

TABLE 99-1 Food and Drug Administration Categorization of Drug Risk in Pregnancy

ANTIMICROBIAL AGENTS Antimicrobial medications are frequently used during pregnancy. All of these agents enter the fetal circulation to some extent. The potential teratogenic effects are unknown for some antimicrobials. Information on the safety of newer extended-spectrum or late-generation agents is limited. 12 Table 99-2 lists known pregnancy-related contraindications to some frequently used antibiotics.

Getting to Know Anxiety

Getting to Know Anxiety

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