Anything a pregnant woman ingests or is exposed to could potentially affect her fetus. This is problematic for health care providers who must treat a variety of conditions during pregnancy. In fact, over 60% of American women receive a prescription for at least one medication during pregnancy. This figure is about 99% for women in France, over 70% for Hungarian women, and over 46% for Finnish women. The most common conditions for which medications are prescribed include gastrointestinal, infectious, dermatologic, psychologic, or psychiatric disorders and to relieve pain.

Generally, whatever medication would be given to a nonpregnant woman is the appropriate choice in pregnancy. In order to be aware of the few exceptions or how to choose between several available options requires knowledge of teratology and alterations in drug metabolism related to pregnancy. Teratology is the study of abnormal development or the production of defects in the fetus. Birth defects affect 2% to 3% of all neonates. With longer follow-up, at least 5% of individuals are affected by a birth defect. Exogenous causes of birth defects, including drugs or chemical exposures, account for almost 10% of birth defects. Thus, at least 0.2% to 0.3% of pregnancies are affected by a birth defect due to a teratogen.

The Food and Drug Administration (FDA) introduced a drug classification system in 1979 to discourage nonessential use of medication during pregnancy. Drugs are classified as A, B, C, D, or X, with the latter being the most teratogenic. There has been growing perception that the FDA classification has led to excessive maternal anxiety and unnecessary pregnancy termination. Several years ago, the FDA began evaluating a revised labeling system for drugs and biologics to include a description of the drugs based on clinical management, summary of risk assessment, and discussion of data. This initiative, begun in the late 1990s, has so far yielded little change in the old classification system. The situation is exemplified by data published in 2002 that shows that over 90% of drug treatments approved between 1980 and 2000 still had undetermined teratogenic risk!

Many health care providers continue to use the FDA classification system but, it is probably more useful to use the myriad commercial drug databases that are frequently updated as new information becomes available. Free resources are also available on the Internet.

How much drug the fetus will be exposed to is determined by a complex interaction of many factors, including how the agent is absorbed, the volume of distribution, metabolism, and excretion. Absorption is via the gastrointestinal tract, skin, lungs, or after parenteral administration. Pregnancy alters absorption in a variety of ways, including prolongation of gastric emptying time by the increased progesterone. The volume of distribution is generally increased during pregnancy. Estrogen and progesterone alter hepatic enzyme activity with varying affects on drug metabolism and clearance depending on the precise pathway. Renal excretion is generally increased during pregnancy. Other factors affect precisely how much drug crosses the placenta, which is influenced by several factors. Lipid-soluble substances readily cross the placenta, and water-soluble substances pass less well. Those with greater molecular weight also cross the placenta less easily. The degree to which a drug is bound to plasma protein influences the amount of drug that is free to cross. Virtually all drugs cross the placenta to some degree, with the exception of large organic ions such as heparin and insulin. Active placental transfer must also be considered.

Other concepts related to teratology include specificity, timing, dose, maternal physiology, embryology, and genetics. Specificity indicates that a substance may be teratogenic in some species but not others. For example, thalidomide produces phocomelia in primates but not rodents. Often, animal data of either safety or teratogenic effect is not necessarily applicable to humans. Timing also is critical. When administered between 35 and 37 days, thalidomide
produces ear malformations, but between 41 and 44 days, it produces amelia or phocomelia. Dosage also is important. In most cases, administration of a low dose will result in no effect, while malformations occur at intermediate doses and death at higher doses. Death may cause organ-specific teratogenic action to go unnoticed. The route of administration, possibly secondary to absorption, also is important. Small doses over several days may have an effect different from the same total dose given at once. Sequential dosing as opposed to a bolus may induce an enzyme to metabolize the substance that potentially causes less damage. Constant exposure may destroy cells, which would have catabolized the drug if administered in periodic doses. As noted previously for thalidomide, timing of exposure relative to embryologic events is important. Teratogen exposure in the first 2 to 3 weeks after conception is generally thought to have no effect or result in spontaneous loss (all-or-nothing phenomenon). The period of susceptibility to teratogenic agents is during the period of organogenesis, which occurs primarily at 3 to 8 weeks postconception (35 to 70 days after the last menstrual period [LMP]) or to 10 weeks from the LMP. After this period, embryonic development is characterized primarily by increasing organ size (10 to 12 weeks). Thus, the principal effect of exposure will be growth restriction and/or effects on the nervous system and gonadal tissue. These systems continue to develop throughout pregnancy. During organogenesis, each organ system will have different critical periods of sensitivity. A teratogen can act by causing cell death, altering tissue growth (hyperplasia, hypoplasia, or asynchronous growth), or interfering with cellular differentiation or other basic morphogenic processes.

The genetic makeup of the mother and fetus can affect individual susceptibility to a drug. Fetuses with low levels of the enzyme epoxide hydrolase may be more likely to manifest the fetal hydantoin syndrome than those with normal levels of epoxide hydrolase. Combinations of agents may produce different degrees of malformation and/or growth restriction than if given individually. Fetuses whose mothers are on combination antiepileptic agents are at the highest risk for malformations, including neural tube defects and facial dysmorphic features.

Most drug therapy does not require cessation of nursing because the amount excreted into breast milk is small enough to be pharmacologically insignificant.

Antibiotics are widely used during pregnancy to treat a variety of disorders, including upper respiratory tract infections and urinary tract infections (Table 8.1). Pregnant patients are particularly susceptible to vaginal yeast infections. This is one reason that antibiotics should be used only when clearly indicated. Therapy with antifungal agents may be necessary after the course of antibiotic therapy.

The common cold is the most frequent acute illness, and most colds are self-diagnosed and treated. Medicines used to treat symptoms associated with the common cold are among the most common used drugs in pregnancy. Most patients complain of fatigue, malaise, rhinorrhea, nasal congestion, cough, and sore throat. The cold can be caused by a variety of viruses, rhinoviruses, coronaviruses, respiratory syncytial virus, adenovirus, parainfluenza and influenza virus, and others. Therefore, in the absence of a complicating superinfection with bacteria, antibiotic treatment is not appropriate.

The most common treatments are used to address the listed symptoms and include antihistamines, decongestants, and cough suppressants.

While the cold is the most common acute illness during pregnancy, asthma is the most common chronic respiratory condition. About 5% of pregnancies are complicated by asthma, which may cause increases in preterm birth, low birth weight, and other complications. Whether aggressive and active management reduces these risks to the background level is a controversial issue. Asthma is characterized by airway inflammation and hyperreactivity.

Treatment of the asthmatic should start with reduction of environmental factors that worsen disease. All patients should receive the influenza vaccination yearly. Allergens should be avoided, as should both active and passive exposures to cigarette smoke. For patients who do not respond optimally to these environmental alterations, a variety of pharmacologic treatments are available (Table 8.3).