Triprolidine

Pregnant women often ask their family physicians questions about the safety of medications and the risks that may be associated with their daily activities. Family physicians--both those who practice obstetrics and those who do not--should be prepared to answer these common pregnancy-related questions.

With the exception of the use of over-the-counter medications, many of the issues that are of concern to pregnant women have not been perceived as medical problems. Consequently, physicians may find that they have very little objective knowledge to convey to their patients.

This article provides information family physicians can use in answering some of the questions that are most commonly asked early in pregnancy. More detailed sources of information are listed at the end of the article.

Medical and Dental Exposures During Pregnancy

OVER-THE-COUNTER MEDICATIONS

Cough and cold medications are among the drugs most commonly used during pregnancy. Antihistamines such as chlorpheniramine and triprolidine have a long history of use and are not associated with an increased risk to the the mother or the fetus.[1-3] Earlier studies reported an increased incidence of birth defects associated with maternal use of brompheniramine, but more recent studies have not confirmed this finding.[1-3]

A small increase in birth defects (none serious) has been noted in the infants of women who used decongestants during pregnancy.[2,3] If a decongestant is indicated, pseudoephedrine has the best safety record during pregnancy and is preferred over other decongestants.[3]

Preparations containing guaifenesin and/or dextromethorphan are recommended for the treatment of cough in pregnant women.[2-4] lodine-saturated cough medications should be avoided because of the potential for thyroid toxicity in the newborn.[3]

In addition to cough and cold preparations, analgesics are often used in pregnancy Acetaminophen is considered the nonnarcotic analgesic of choice because of its well-established safety record in all trimesters.[2,4,5]

Acetylsalicylic acid (aspirin), ibuprofen and naproxen should be used cautiously during pregnancy because of the association of nonsteroidal anti-inflammatory agents (NSAIDs) with adverse effects on fetal renal function[6] and transient narrowing of the ductus arteriosus.[7] Furthermore, aspirin has been noted to increase maternal and neonatal blood loss following delivery, even when the medication is discontinued up to three weeks before delivery.[8]

While low-dose aspirin therapy is being used more frequently to prevent pre-eclampsia and low birth weight, acetaminophen is the analgesic that poses the least risk to the mother and the fetus. Only when acetaminophen is contraindicated should aspirin and NSAIDs be used for pain relief.

Fiber laxatives and over-the-counter antacids are other types of medications frequently used during pregnancy. Because fiber laxatives are not systemically absorbed, they do not increase risks during pregnancy. Antacids also pose little risk to the developing fetus, but these agents may bind iron in the gastrointestinal tract. Thus, excessive use of antacids during pregnancy could contribute to iron-deficiency anemia.[9] Ideally, pregnant women should minimize their intake of antacids by avoiding foods and beverages that may exacerbate heartburn, by discontinuing smoking and by eating small, frequent meals.

IMMUNOTHERAPY AND ALLERGY TREATMENT

Allergen immunotherapy may be a valuable treatment option for pregnant women with allergies.[10,11] Women with perennial rhinitis who are intolerant of medications or who have moderate to severe asthma should continue to benefit from immunotherapy during their pregnancy. Since newer antihistamines and some antiasthmatic drugs cannot yet be recommended for use in pregnant women,[11] immunotherapy may be valuable in reducing the severity of symptoms and complications during pregnancy. Some pregnant women on maintenance doses of immunotherapy may experience an increased reaction to allergen preparations. In these cases, the maintenance dose may be reduced by approximately one-half until delivery in order to reduce the risk of anaphylaxis from allergy injections.[11]

DENTAL PROCEDURES

The major concerns of women who need dental care during pregnancy are exposure to anesthetic agents and diagnostic radiographs. Because of low systemic absorption, local anesthetics used in appropriate amounts are acceptable in pregnancy. Nitrous oxide is also acceptable for sedation, but it is less desirable than local anesthesia because it is systemically absorbed and crosses the placenta. However, nitrous oxide has not been shown to be teratogenic.[12]

Dentists often recommend that all elective dental treatment, except plaque control, be avoided during the first trimester of pregnancy However, based on the safety record of local anesthetic agents, this recommendation appears to be overly cautious.

Normal preventive and restorative procedures are not contraindicated at any time during pregnancy. In fact, existing evidence suggests that the bacterial overgrowth from dental caries could increase the risk of transmission of infection to the newborn.[13]

The risk of fetal malformation from diagnostic dental radiographs in an appropriately shielded patient is extremely low.[14] However, dental radiographs should be obtained only when necessary, and leaded aprons should always be used for shielding. Women and dentists can be reassured that treatment during early pregnancy poses little or no risk and should be provided when necessary.

Other Common Exposures

CAFFEINE

Although caffeine does not appear to have a teratogenic effect,[15-19] some studies have suggested that caffeine is a risk factor for low birth weight.20-25 However, other more recent studies that controlled for potential confounding factors, such as smoking, have not shown an association between moderate caffeine consumption and low birth weight.[26,27]

Heavy caffeine consumption during pregnancy may cause caffeine withdrawal in newborns. Infants with caffeine withdrawal have feeding difficulties, vomiting, excessive crying, irritability and poor sleep patterns. Because neonates metabolize caffeine poorly, the half-life of caffeine in the neonate is about four days.[28], This prolonged half-life may cause withdrawal symptoms to persist for days to weeks.29 Women who consume large amounts of caffeine products should be advised to curtail their caffeine intake late in pregnancy to reduce the risk of neonatal caffeine withdrawal.

Thus, low to moderate caffeine consumption is not associated with significant risks during pregnancy. However, consumption of large amounts of caffeine has been associated with increased fetal loss.[30] Because of this association and the potential links between heavy caffeine use and both low birth weight and caffeine withdrawal in the neonate, women should be advised to moderate their consumption of caffeine while they are pregnant. Furthermore, pregnant patients should be informed about sources of caffeine other than coffee, including tea, colas, chocolate and over-the-counter drugs.

ASPARTAME

Pregnant women often ask whether they should curtail their consumption of beverages and foods sweetened with aspartame (NutraSweet). There have been no reported studies of adverse fetal or maternal effects from aspartame, either in laboratory animals or humans.[31-33]

Studies have found that patients with phenylketonuria can consume large doses of aspartame (34 to 100 mg per kg) without a significant increase in baseline phenylalanine levels.[34,35] Nevertheless, patients with phenylketonuria should avoid phenylalanine consumption, and warnings directed at these patients appear on all aspartame-containing products.

HAIR CARE PRODUCTS AND COSMETICS

Many pregnant women question whether specific hair care products, such as dyes, straighteners (relaxers) and permanent wave solutions, can harm the developing fetus. Studies in animals and humans have failed to identify any specific risks for pregnant women from these products.[2] Therefore, exposure to these agents should pose no significant increase in risk to the fetus.

No data are available to determine whether an association exists between hair spray or shampoos and adverse outcomes of pregnancy. Therefore, no firm statement can be made concerning the risks of using these products during pregnancy.

Little information is available regarding the risks to the fetus from cosmetics (including facial make-up and nail polish), perfumes, soaps, lotions and antiperspirants or deodorants. Considering the widespread use of these products during pregnancy, an association with one particular product would be difficult to find. Without specific evidence that cosmetics and other personal care products affect pregnancy outcomes, most physicians advise patients that these agents pose no increased risk to the fetus.

VIDEO DISPLAY TERMINALS

Many pregnant women are employed in clerical, sales or administrative positions that require the use of video display terminals. Reports of clusters of birth defects and early miscarriages in workers who spent considerable portions of their time using computer video display terminals have raised concerns about the potential risks to pregnant women who use these instruments.

Following anecdotal reports of miscarriages in women who used video display terminals, larger epidemiologic studies have investigated whether an association exists between exposure to these terminals and adverse pregnancy outcomes.[36] Taken together, these studies have not demonstrated a convincing association between miscarriage, low birth weight or birth defects and the use of video display terminals.[31,36]

HOUSE PAINT

Pregnant women may have an occupational exposure to paint, or they may be exposed to paint at home. Most studies that suggest an association between paint exposure and adverse pregnancy outcomes are either case reports or retrospective studies that deal with chronic occupational exposure to fumes.[37] The data from these studies are insufficient to show a cause-and-effect relationship between paint exposure and fetal harm. However, because oil-based paints and paint thinners contain a number of aromatic organic solvents, exposure to these products should be limited or avoided, particularly during the first trimester of pregnancy.[2]

Brief exposure to water-based paints and similar compounds in a well-ventilated area should not pose a significant risk to the fetus. Pregnant women should be reminded to use all paints as directed by the manufacturer. For example, paints labeled for outdoor use should not be used indoors.

A more complete guide to chemical exposures in pregnancy is available in a number of computer databases and toxicology textbooks. A listing of some of these sources is provided at the end of this article.

INSECTICIDES

Since homeowners purchase more than 50 million lb of pesticides annually, exposure to these agents during pregnancy is not trivial. Most insecticides are very lipid-soluble, and they are readily absorbed, even with limited exposure.

Despite the quantity of pesticides used by homeowners, surprisingly little information is available about the effects of exposure during pregnancy. Many pesticides are known to be mutagens, but whether they are teratogenic is less clear.

In general, pregnant women probably should not apply pesticides in the home or the yard. In particular, they should avoid the use of fumigants. Pesticides should be applied by someone other than the pregnant woman, and only local application of a liquid, spray or dust should be done. Contact with products such as insecticide strips and flea collars should also be avoided, since these products may pose some increased risk during pregnancy.[38]

SEAT BELT USE

Maternal trauma is the leading nonobstetric cause of fetal death.[39] A study[40] of 441 pregnant women involved in motor vehicle accidents showed that maternal mortality increased sixfold and fetal mortality increased fivefold in cases in which the woman was ejected from the automobile. Consequently, the use of seat belts is recommended to decrease maternal and fetal trauma in the event of a motor vehicle accident.

Use of a conventional lap belt alone has been implicated as a causative agent of uteroplacental accidents and fetal injuries.[41,42] The best protection is provided by the diagonal shoulder strap with a lap belt (i.e., a three-point restraint).[43] The diagonal strap should pass over the shoulder and across the chest between the breasts. The lap strap should he across the upper thighs. Thus, the straps should be above and below the "bump" of pregnancy--not over it. Use of the three-point restraint distributes the energy of the impact over the chest wall and the pelvis.[44,45]

Final Comment

The range of possible problems that women may encounter in early pregnancy is broad and complex. While this review article cannot address an of the concerns in early pregnancy, the information provided may be helpful in answering some of the questions most frequently posed by pregnant women. This information is summarized in Table 1.

Family physicians who practice obstetrics should expect these questions and should be prepared to answer them. They need to tell their patients when no information is available about a particular concern. At no time should an exposure or drug be considered safe just because no data exist.

Family physicians who do not include obstetrics in their practice also should be well-informed about issues that women face early in pregnancy and should be prepared to offer appropriate advice to patients. Inappropriate advice or delays in obtaining information until obstetric care is established may cause anxiety and needless changes in work and living habits for pregnant women.

Sources of Additional Information

Overviews of drug use in pregnancy Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs in pregnancy and lactation. 3d ed. Baltimore: Williams & Wilkins, 1990.

Folb PI, Dukes MN, eds. Drug safety in pregnancy New York: Elsevier Press, 1990.

Niebyl JK, ed. Drug use in pregnancy. Philadelphia: Lea & Febiger, 1988.

Use of specific drugs or chemicals in pregnancy Shepard TH. Catalog of teratogenic agents. 7th ed. Baltimore: Johns Hopkins University Press, 1992.

Schardein JL. Chemically induced birth defects. 2d ed. New York: Dekker, 1993.

Description of computerized databases Lione A. The use of available data sets to define the safety of occupational chemical exposures during pregnancy. Semin Perinatol 1993;17:28-36.

REFERENCES

[1.] Heinonen OP, Slone D, Shapiro S, Gaetano LF, Kaufman DW, et al, eds. Birth defects and drugs in pregnancy. Littleton, Mass.: Publishing Sciences Group, 1977. [2.] Zuber C, Hom M, Vought L, Donnenfeld AE. Common chemical exposures in pregnancy: cosmetics, paint fumes, and cold medications. Postgrad Obstet Gynecol 1992;12(1):1-6. [3.] Niebyl JR, Repke JT. Treatment of the common cold. In: Niebyl JR, ed. Drug use in pregnancy. 2d ed. Philadelphia: Lea & Febiger, 1988:235-8. [4.] Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 3d ed. Baltimore: Wilkins & Wilkins, 1990:2-5,290. [5.] Hill LM, Kleinberg E Effects of drugs and chemicals on the fetus and newborn. Mayo Clin Proc 1984;59:707-16. [6.] Restaino I, Kaplan BS, Kaplan P, Rosenberg HK, Witzleben C, Roberts N. Renal dysgenesis in a monozygotic twin: association with in utero exposure to indomethacin. Am J Med Genet 1991;39: 252-7. [7.] Moise KJ Jr, Huhta JC, Sharif DS, Ou CN, Kirshon B, Wasserstrum N, et al. Indomethacin in the treatment of premature labor. Effects on the fetal ductus arteriosus. N Engl J Med 1988;319:327-31. [8.] Stuart MJ, Gross SJ, Elrad H, Graeber JE. Effects of acetylsalicylic-acid ingestion on maternal and neonatal hemostasis. N Engl J Med 1982;307:909-12. [9.] Root B, King JC. Maternal nutrition. In: Creasy RK, Resnik R, eds. Maternal-fetal medicine: principles and practice. Philadelphia: Saunders, 1989:188. [10.] Metzger WJ. Indications for allergen immunotherapy during pregnancy. Compr Ther 1990;16(3):17-26. [11.] Metzger WJ, Turner E, Patterson R. The safety of immunotherapy during pregnancy J Allergy Clin Immunol 1978;61(4):268-72. [12.] Conover WB, Key TC. Maternal gastrointestinal and hepatic diseases. In: Creasy RK, Resnick R, eds. Maternal-fetal medicine: principles and practice. Philadelphia: Saunders, 1984:956. [13.] Mishkin DJ, Javed T. Dental diseases. In: Gleicher N, ed. Principles and practice of medical therapy in pregnancy. Norwalk, Conn.: Appleton & Lange, 1992:947-9. [14.] Danforth RA, Gibbs SJ. Diagnostic radiation: what is the risk? J Calif Dent Assoc 1980;8:28-35. [15.] Soyka LF. Caffeine ingestion during pregnancy: in utero exposure and possible effects. Semin Perinatol 1981;5:305-9. [16.] Aldridge A, Bailey J, Neims AH. The disposition of caffeine during and after pregnancy. Semin Perinatol 1981;5:310-4. [17.] Rosenberg L, Mitchell AA, Shapiro S, Slone D. Selected birth defects in relation to caffeine-containing beverages. JAMA 1982;247:1429-32. [18.] Kurppa K, Holmberg PC, Kuosma E, Saxen L. Coffee consumption during pregnancy and selected congenital malformations: a nationwide case-control study. Am J Pub Health 1983;73:1397-9. [19.] Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ryan KJ. No association between coffee consumption and adverse outcomes of pregnancy. N Engl J Med 1982;306:141-5. [20.] Furuhashi N, Sato S, Suzuki M, Hiruta M, Tanaka M, Takahashi T. Effects of caffeine ingestion during pregnancy. Gynecol Obstet Invest 1985;19:187-91. [21.] Caan BJ, Goldhaber MK. Caffeinated beverages and low birthweight: a case-control study. Am J Pub Health 1989;79:1299-300. [22.] Watkinson B, Fried PA. Maternal caffeine use before, during and after pregnancy and effects upon offspring. Neurobehav Toxicol Teratol 1985; 7:9-17. [23.] Berkowitz GS, Holford TR, Berkowitz RL. Effects of cigarette smoking, alcohol, coffee and tea consumption on preterm delivery. Early Hum Dev 1982; 7:239-50. [24.] Hogue CJ. Coffee in pregnancy [Letter]. Lancet 1981;1(8219):554. [25.] Martin TR, Bracken MB. Association between low birth weight and caffeine consumption during pregnancy. Am J Epidemiol 1987;126:813-21. [26.] Mills JL, Holmes LB, Aarons JH, Simpson JL, Brown ZA, Jovanovic-Peterson LG, et al. Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation. JAMA 1993; 269:593-7. [27.] Godel JC, Pabst HF, Hodges PE, Johnson KE, Froese GJ, Joffres MR. Smoking and caffeine and alcohol intake during pregnancy in a northern population: effect on fetal growth. Can Med Assoc J 1992:147:181-8. [28.] Aldridge A, Aranda JV, Neims AH. Caffeine metabolism in the newborn. Clin Pharmacol Ther 1979;25:447-53. [29.] Thomas DB. Neonatal abstinence syndrome [Letter]. Med J Aust 1988;148:598. [30.] Infante-Rivard C, Fernandez A, Gauthier R, David M, Rivard GE. Fetal loss associated with caffeine intake before and during pregnancy. JAMA 1993; 270:2940-3. [31.] Zuber C, Librizzi RJ, Bolognese RJ. Do aspartame and video display terminals pose pregnancy risks. Postgrad Obstet Gynecol 1989;9(26):1-5. [32.] Aspartame. Review of safety issues. Council on Scientific Affairs. JAMA 1985;254:400-2. [33.] Yost DA. Clinical safety of aspartame. Am Fam Physician 1989;39(2):201-6. [34.] Koch R, Schaeffler G, Shaw NE Results of loading doses of aspartame by two phenylketonuric (PKU) children compared with two normal children. J Toxicol Environ Health 1976;2:459- 69. [35.] Stegink LD, Filer LJ Jr, Baker GL, McDonnell JE. Effect of aspartame loading upon plasma and erythrocyte amino acid levels in phenylketonuric heterozygotes and normal adult subjects. J Nutr 1979;109:708-17. [36.] AMA Council on Scientific Affairs. Health effects of video display terminals. JAMA 1987,257:1508-12. [37.] Scialli AR. Who should paint the nursery? Reprod Toxicol 1989;3:159-64. [38.] Davis JR, Brownson RC, Garcia R. Family pesticide use in the home, garden, orchard, and yard. Arch Environ Contam Toxicol 1992;22:260-6. [39.] Hakanson EY. Trauma to the female genitalia. Lancet 1966;86(6):287-91. [40.] Crosby WM, Costiloe JP. Safety of lap-belt restraint for pregnant victims of automobile collisions. N Engl J Med 1971;284:632-6. [41.] Robovits FE. Traumatic rupture of the pregnant uterus from seat belt injury Am J Obstet Gynecol 1964;90:828-9. [42.] Crosby WM. Pathology of obstetrical injuries. In: Brinkhous KM, ed. Accident pathology: proceedings. Chapel Hill, N.C.: University of North Carolina 1970:204-17. [43.] Crosby WM, King Al, Stout LC. Fetal survival following impact: improvement with shoulder harness restraint. Am J Obstet Gynecol 1972;112:1101-6. [44.] Pearce M. Seat belts in pregnancy [Editorial]. BMJ 1992;304:586-7. [45.] Griffiths M, Usherwood MM, Reginald PW Antenatal teaching of the use of seat belts in pregnancy. BMJ 1992;304:614.

WILLIAM J. HUESTON, M.D. is assistant professor of family medicine and practice at the University of Wisconsin, Madison. He also serves on the faculty of the Eau Claire (Wis.) Family Practice Residency Program.

GAYLEEN M. EILERS, M.D. is assistant professor of family medicine and practice at the University of Wisconsin and is also on the faculty of the Eau Claire Family Practice Residency Program.

DANA E. KNG, M.D. is an assistant professor of family medicine at East Carolina University School of Medicine, Greenville, N.C.

VICTOR G. MCGLAUGHLIN, M.D. is the undergraduate coordinator for the Family Practice Residency Program at Womack Army Medical Center, Fort Bragg, N.C.

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