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Complications during pregnancy and some birth defects are often the result of a patient’s age, genetics, disease, diet, and lifestyle (as well as the use of substances such as tobacco and alcohol). Unfortunately, the delivery of medical and dental treatment to a pregnant patient, including the administration of medications, may also produce complications and adverse effects for the patient and the fetus.
While there has been much research into the teratogenicity (tendency to produce birth defects) of drugs used in medicine and dentistry, there is also much misinformation and misunderstanding regarding the use of medications during pregnancy. This increases the likelihood that a pregnant patient may take a medication that should be avoided or avoid a medication that she should be taking. Major determinants of a medication’s likeliness to produce teratogenic effects include the medication dosage, the duration of pharmacologic treatment, and the trimester of pregnancy during which the medication is used.1
During pregnancy, there are profound changes in multiple organ systems, especially the cardiovascular and respiratory systems, which may influence medication administration. Due to increased hormonal activity, there is an increase in sodium and fluid retention and, thus, an increase in plasma volume. This results in an increase in cardiac output and increased heart rate. There is also an increase in fluids in the respiratory tract which, when combined with anatomical changes that elevate the diaphragm, result in decreased respiratory capacity.2
While these changes in the pregnant patient’s physiology may be problematic enough for the safe delivery of dental care, they may, unfortunately, also require increased doses of medications in order for the patient to achieve desired therapeutic effects. However, medications are transferred across the placenta to the fetus through simple diffusion via a concentration gradient. As a result, increasing the dose of medications to compensate for maternal physiologic changes may also result in an increased transfer of medication to the fetus and, thus, an increased risk of potential teratogenic effects. Although much has been written about the “placental barrier,” it is clear that almost every medication passes from the mother to the fetus to some extent.3
Therefore, when considering the use of a medication during pregnancy, the potential benefit to the pregnant patient must always be weighed against the potential risk to the fetus. However, not all women of childbearing age know that they may indeed be pregnant. Thus, the possibility that the patient is already pregnant, or may become pregnant while still taking the medication, should also always be considered. Although the placental membrane is relatively thick and somewhat resistant to medication transfer during the first trimester, many major teratogenic effects still occur as a result of medication exposure during this critical organ formation period. The period of greatest risk to the fetus for teratogenic effects of medications is from 5 to 10 weeks’ gestation.
Although most elective dental procedures can be postponed until after delivery, there are circumstances, such as severe pain or advanced infection, in which dental treatment for a pregnant patient is required. The goal of any dental treatment plan for a pregnant patient, obviously, is to avoid adverse reactions and potential teratogenic effects, while delivering safe and effective dental care. To determine the risks associated with the use of medications in pregnancy, the US Food and Drug Administration (FDA) has classified medications based on the level of risk they pose to fetuses (Table I).4
Medications commonly used in dentistry that may be of concern during pregnancy include local anesthetics with epinephrine, analgesics and anti-inflammatory agents, and antimicrobial agents.5
The local anesthetic agents lidocaine and prilocaine are considered safe to administer to a pregnant patient (both are considered Category B drugs by the FDA) since they have not demonstrated any teratogenic effects in humans, even in doses far exceeding the maximum recommended daily dose. The use of prilocaine does warrant some additional caution since it has the potential to cause methemoglobinemia in predisposed individuals. The other available amide local anesthetic agents (articaine, bupivacaine, and mepivacaine) are all considered Category C drugs. Topical anesthetic agents used in dentistry include benzocaine, lidocaine, and tetracaine. Of these, only lidocaine is considered a Category B drug; the rest are all considered Category C drugs.4
However, it is important to note that all local anesthetic agents can cross the placenta and cause central nervous system and cardiovascular depression. Thus, it is essential to limit these agents to the lowest possible dose required for effective pain control. Further, it is imperative to employ proper technique (performing aspiration, injecting slowly) to minimize the risk of intravascular injection. As an endogenous substance, epinephrine is considered safe to administer to the pregnant patient. In general, the benefits of adding epinephrine—improved quality and duration of anesthesia, and reduced overall doses, plasma concentrations, and potential adverse effects—are considered to outweigh the potential risks.6
Non-opioid analgesics commonly used in dentistry include aspirin, acetaminophen, ibuprofen, and naproxen. Of these, only acetaminophen (Tylenol) is classified as a Category B drug. It is generally accepted as safe for use during pregnancy (in regular doses) for the treatment of mild to moderate pain. All the other non-opioid analgesics are considered Category C or D drugs. Since acetaminophen has minimal, if any, anti-inflammatory activity, the benefit of using non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen and naproxen, for the control of acute dental pain may outweigh the potential risk to the fetus. However, these medications should be used cautiously during pregnancy, especially during the third trimester, since they have been shown to inhibit labor, prolong gestation, and promote premature changes in circulation—all of which may be life-threatening to the fetus.6
Opioid analgesics used commonly in dentistry include codeine, hydrocodone, and oxycodone. Of these three medications, only oxycodone is considered a Category B drug while the others are considered Category C drugs. Even when combined with acetaminophen, these medications are rarely used as first-line agents in treating dental pain in pregnant patients, since they lack anti-inflammatory activity. In addition, since their use during pregnancy has been associated with fetal respiratory depression and postpartum withdrawal, these medications should be used cautiously and only when the benefit to the pregnant patient clearly outweighs the risk to the fetus.6
Antimicrobial agents commonly used in dentistry include antibacterial agents and, to a lesser extent, antifungal agents. The antibacterial agents used in dentistry include amoxicillin, azithromycin, cephalexin, clindamycin, metronidazole, and penicillin. All of these medications are considered Category B drugs and are generally thought to be safe to use during pregnancy. If an antifungal agent is necessary, such as for the treatment of oral candidiasis, nystatin suspension is generally thought to be the safest agent to use during pregnancy. Although it is considered a Category C drug, nystatin is poorly absorbed after oral administration and, thus, the risk to the fetus is greatly reduced.6
When it is apparent that dental care for a pregnant patient cannot be postponed until after delivery and therapy is urgently required, the goal of any dental treatment plan is to avoid potential teratogenic effects whenever possible. Therefore, when considering the use of a medication during pregnancy, it is imperative that the potential benefit to the pregnant patient is weighed against any potential risk to the fetus.
1. Niebyl J, Simpson J. Teratology and drugs in pregnancy. Global Library of Women’s Medicine. Available at: http://www.glowm.com/section_view/heading/Teratology%20and%20Drugs%20in%20Pregnancy/item/96#5191.
2. Madappa T, Sharma S. Pulmonary disease and pregnancy. Alterations in pulmonary physiology during pregnancy. Available at: http://emedicine.medscape.com/article/303852-overview.
3. Vähäkangas K, Myllynen P. Drug transporters in the human blood-placental barrier. Br J Pharmacol. 2009;158(3):665-678.
4. United States Food and Drug Administration. Federal Register. 1980;44:37434-37467.
5. Mendia J, Cuddy MA, Moore PA. Drug therapy for the pregnant dental patient. Compend Contin Educ Dent. 2012;33(8):568-576.
6. Jeske AH. Mosby’s Dental Drug Reference. 11th ed. St. Louis, MO: Mosby Elsevier; 2013.
About the Author
In addition to his profession of pharmacy, Thomas Viola, RPh, CCP, also serves the professions of dentistry, dental hygiene, and dental assisting as an educator, published writer, and professional speaker. He is a member of the faculty of seven dental hygiene and dental assisting programs, as well as national board exam review courses, serves as a contributor to several dental professional journals, and serves as a contributor to Mosby’s Dental Drug Reference. He has presented hundreds of continuing education courses, nationally and internationally, in the areas of dental pharmacology and local anesthesia. Visit his website at www.thomasviola.com.