First trimester

Any discussion of the use of local anesthetics both during pregnancy and the postpartum period requires a brief explanation of teratogenicity (the capability of an agent to initiate fetal malformation) and mutagenicity. The specific definition of a mutagen involves an agent that can alter genetic material and increase the incidence of mutations compared with background levels. A teratogen is an agent that initiates abnormalities of fetal development. The primary focus here is teratogenicity of local anesthetics.

Birth defects occur in about 3% of live births each year in the United States, and have been the leading cause of infant mortality. Drug and chemical exposure is believed to be responsible for about 1% of these occurrences. Birth defects account for 20% of all infant deaths and are consequently the leading cause of infant mortality in the United States. Extensive diagnoses or treatments of birth defects are required for 7% to 10% of all children, and approximately 65% of birth defects have no identifiable cause. Intrauterine vulnerability of the embryo led to the development and refinement of The Six Principles of Teratology, as found in Jim Wilson’s 1959 monograph Environment and Birth Defects. For our purposes, the principles that apply to teratogenic effects are genotype, developmental stage, agent-specific actions, and fetal absorption.

Early investigations were centered on gross deformities in animal models, but, for human studies, pregnancy registries serve as large prospective studies that record outcomes and provide information about possible risks of medications or exposures in pregnancies. Exposure to teratogens can result in a wide range of structural abnormalities such as cleft lip, cleft palate, dysmelia, anencephaly, or ventricular septal defect. In most cases, specific agents produce a specific teratogenic response. There is a long list of agents and environmental factors that has been discovered to be teratogenic, and commonly used local anesthetics have not been included. Teratogenic agents are categorized as radiation, infections, metabolic imbalances, drugs, or environmental chemicals.

By the end of the first month of development following fertilization, the fetus has a closed neural tube, hematopoesis has begun, and a primitive heart is present. The embryonic period reaches from conception to the 10th gestational week, with the embryo then becoming a fetus and the first trimester culminating at the end of the 13th week. Organogenesis has occurred, the heart is beating, there is fetal movement, limb buds are developing and the fetus can already make a fist. All major structures are formed by this point and continue to develop throughout the gestational period. Once the embryo has become a fetus, the risk of environmental damage is reduced, but still present to a degree.

During this early stage of pregnancy, it is crucial to be aware that a pregnancy may exist. Because the possibility of embryonic or fetal damage is a concern, a missed menstrual period may be the first sign; however, a urine pregnancy test may be suggested when there is doubt. Human chorionic gonadotropin (hCG), a glycoprotein secreted by the placenta shortly after implantation, is measured in urine in milli-international units (mIU). Urine tests reacting to a level of 20 mIU/mL hCG are more sensitive and can detect a pregnancy earlier (at approximately 8 days) than those requiring a higher level. Blood tests can confirm a positive urine test. Over-the-counter testing products are required to list their sensitivity level in their packaging, aiding choice in home product use. On average, a pregnant woman’s level of hCG is approximately 25 mIU/mL at 10 days after ovulation and 100 mIU/mL at about 14 days. Home pregnancy test kits used by experienced technicians are almost as accurate as professional laboratory testing (97.4%), but, when used by consumers, the accuracy can be reduced to 75%. Improper usage may cause both false negatives and false positives. If your patient is at risk for pregnancy, careful consideration must be given to the possible negative outcomes before initiating treatment. Consultation with the patient’s obstetrician is the customary practice.

Most drugs cross the placenta by simple diffusion; hence our concern for the possibility of their teratogenic effects. Although the embryo is within the predifferentiation period from 2 to 4 weeks it is resistant to teratogenic effects. The most risk occurs following this period, when organogenesis takes place, during the 4 to 10 weeks following the last menstrual period. Because of the level of sensitivity of the embryo and fetus, it is generally recommended that any dental treatment be deferred until the first trimester is complete.

If emergent care is required in the first trimester, the negative consequences of allowing an active infection to progress untreated in a pregnant patient outweigh the risks of providing care. Radiographs may be taken as necessary, with appropriate precautions being taken to protect the fetus and the patient, such as a lead apron, a tightly collimated beam, and high-speed film. In choosing the local anesthetic for care in this situation, both the maternal and fetal effects are considered. The local anesthetic with the longest record of use is lidocaine. Because lidocaine is not available in a dental cartridge without epinephrine, the effects of this second drug become an issue. The use of 1:100,000 epinephrine as the vasoconstrictor in accidental intravascular injection can deliver 10 μg/mL of epinephrine. Clinically significant intravascular doses of α-adrenergic agents are to be avoided to maintain appropriate placental perfusion and fetal viability. Normally used dental dosages of local anesthetic with vasoconstrictors, without inadvertent intravascular injection, do not expose the fetus or uterus to significant levels of epinephrine. The possibility of the formation of methemoglobinemia in the fetus with the use of prilocaine, the reduced level of fetal protein binding, as well as reduced liver metabolism, give lidocaine the least risk.