Parasympatholytic
PREGNANCY RECOMMENDATION: Human Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Although the human data describing pregnancy outcomes are limited, there is no evidence of embryo or fetal harm.
FETAL RISK SUMMARY
Atropine, an anticholinergic, rapidly crosses the placenta (1–4). Atropine exposure in the 1st, 2nd, and 3rd trimesters was estimated in one study to be 11.3, 6.7, and 6.3/1000 women, respectively (5). The drug has been used to test placental function in high-risk obstetric patients by producing fetal vagal blockade and subsequent tachycardia (6).
IV atropine (0.5 mg) caused a decrease of 10%–100% in fetal breathing in 13 of 15 fetuses, an increase of 300% in 1 fetus, and no effect in another (7). The decrease in fetal breathing occurred approximately 2 minutes after administration of the drug and lasted 5–10 minutes. No fetal hypoxia was observed, nor was there an effect on fetal heart rate or beat-to-beat variability.
The Collaborative Perinatal Project monitored 50,282 mother–child pairs, 401 of whom used atropine in the 1st trimester (8, pp. 346–353). For use anytime during pregnancy, 1198 exposures were recorded (8, p. 439). In neither group was evidence found for an association with malformations. However, when the group of parasympatholytics were taken as a whole (2323 exposures), a possible association with minor malformations was found (8, pp. 346–353).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 381 newborns had been exposed to atropine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 18 (4.7%) major birth defects were observed (16 expected). Specific data were available for six defect categories, including (observed/expected) 4/4 cardiovascular defects, 0/0.5 oral clefts, 1/0 spina bifida, 2/0 polydactyly, 1/1 hypospadias, and 2/0 limb reduction defects. Only with the latter defect is there a suggestion of a possible association, but other factors such as the mother’s disease, concurrent drug use, and chance may be involved.
Atropine has been used to reduce gastric secretions before cesarean section without producing fetal or neonatal effects (9,10). In a study comparing atropine and glycopyrrolate, 10 women in labor received 0.01 mg/kg of IV atropine (11). No statistically significant changes were noted in fetal heart rate or variability nor was there any effect on uterine activity.
A single case of a female infant born at 36 weeks’ gestation with multiple defects, including Ebstein anomaly, was described in a 1989 report (12). In addition to the cardiac defect, other abnormalities noted were hypertelorism, epicanthal folds, low-set posteriorly rotated ears, a cleft uvula, medially rotated hands, deafness, and blindness. The mother had taken Lomotil (diphenoxylate and atropine) for diarrhea during the 10th week of gestation. Because exposure was beyond the susceptible stages of development for these defects, the drug combination was not considered causative. However, a possible viremia in the mother as a cause of the diarrhea could not be excluded as playing a role in the infant’s anomalies.
BREASTFEEDING SUMMARY
The passage of atropine into breast milk is controversial (13). It has not been adequately documented whether measurable amounts are excreted or, if excretion does occur, whether it may affect the nursing infant. Although neonates are particularly sensitive to anticholinergic agents, no adverse effects have been reported in nursing infants whose mothers were taking atropine. The American Academy of Pediatrics classifies the agent as compatible with breastfeeding (14).
References
1.Nishimura H, Tanimura T. Clinical Aspects of The Teratogenicity of Drugs. New York, NY: American Elsevier, 1976:63.
2.Kivalo I, Saarikoski S. Placental transmission of atropine at full-term pregnancy. Br J Anaesth 1977;49:1017–21.
3.Kanto J, Virtanen R, Iisalo E, Maenpaa K, Liukko P. Placental transfer and pharmacokinetics of atropine after a single maternal intravenous and intramuscular administration. Acta Anaesth Scand 1981;25:85–8.
4.Onnen I, Barrier G, d’Athis PH, Sureau C, Olive G. Placental transfer of atropine at the end of pregnancy. Eur J Clin Pharmacol 1979;15:443–6.
5.Piper JM, Baum C, Kennedy DL, Price P. Maternal use of prescribed drugs associated with recognized fetal adverse drug reactions. Am J Obstet Gynecol 1988;159:1173–7.
6.Hellman LM, Fillisti LP. Analysis of the atropine test for placental transfer in gravidas with toxemia and diabetes. Am J Obstet Gynecol 1965;91:797–805.
7.Roodenburg PJ, Wladimiroff JW, Van Weering HK. Effect of maternal intravenous administration of atropine (0.5 mg) on fetal breathing and heart pattern. Contrib Gynecol Obstet 1979;6:92–7.
8.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
9.Diaz DM, Diaz SF, Marx GF. Cardiovascular effects of glycopyrrolate and belladonna derivatives in obstetric patients. Bull NY Acad Med 1980;56:245–8.
10.Roper RE, Salem MG. Effects of glycopyrrolate and atropine combined with antacid on gastric acidity. Br J Anaesth 1981;53:1277–80.
11.Abboud T, Raya J, Sadri S, Grobler N, Stine L, Miller F. Fetal and maternal cardiovascular effects of atropine and glycopyrrolate. Anesth Analg 1983;62:426–30.
12.Siebert JR, Barr M Jr, Jackson JG, Benjamin DR. Ebstein’s anomaly and extracardiac defects. Am J Dis Child 1989;143:570–2.
13.Stewart JJ. Gastrointestinal drugs. In: Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia: ADIS Press, 1981:65–71.
14.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.