Drugs in Pregnancy and Lactation

Fetal Risk Summary

Saccharin is a nonnutritive sweetening agent discovered accidentally in 1879 and used in the United States since 1901 (1). The agent is approximately 300 times sweeter than sucrose (1,2). Saccharin, a derivative of naphthalene, is absorbed slowly after oral ingestion and is rapidly and completely excreted, as the unmetabolized compound, by the kidneys (1). Although a large amount of medical research has been generated concerning saccharin, very little of this information pertains to its use by pregnant women or to its effect on the fetus (1,2).
In pregnant rhesus monkeys administered IV saccharin, fetal accumulation of the sweetener occurred after rapid, but limited, transfer across the placenta (3). Saccharin appeared to be uniformly distributed to all fetal tissues except the central nervous system. Fetal levels were still present 5 hours after the end of the infusion and 2 hours after maternal concentrations were undetectable. A study, published in 1986, documented that saccharin also crosses the placenta to the human fetus (4). Six diabetic women, consuming 25–100 mg/day of saccharin by history, were delivered at 36–42 weeks. Maternal serum saccharin concentrations, measured between 0.5 hour before to 2 hours after delivery, ranged from 20 to 263 ng/mL. Cord blood samples varied from 20 to 160 ng/mL.
Saccharin is not an animal teratogen (3,5,6). No increase in the incidence of spontaneous abortions among women consuming saccharin has been found (7). Concerns for human use focus on the potential carcinogenicity of the agent. In some animal species, particularly after second-generation studies, an increased incidence of bladder tumors was observed (2). However, epidemiologic studies have failed to associate the human use of saccharin with bladder cancer (2). Similarly, no evidence was found in a study of the Danish population that in utero saccharin exposure was associated with an increased risk of bladder cancer during the first 30–35 years of life (2,8). However, at least one investigator believes that these studies must be extended much further before they are meaningful, because bladder cancer is usually diagnosed in the elderly (9).
Because of the limited information available on the risk for humans following in utero exposure to saccharin, the use of this sweetener should be avoided during pregnancy. The Calorie Control Council believes the agent can be safely used by pregnant women (10). However, others recommended avoidance of saccharin or, at least, cautious use of it in pregnancy (1,2,9).

Breast Feeding Summary

Saccharin is excreted into human milk (11). In six healthy women, saccharin, 126 mg/12 fluid ounces, contained in two commercially available soft drinks, was given every 6 hours for nine doses. After single or multiple doses, median peak concentrations of saccharin occurred at 0.75 hour in plasma and at 2.0 hours in milk. Milk concentrations ranged from <200–1056 ng/mL after one dose to 1765 ng/mL after nine doses. The ratios of the concentration-time curves for milk and plasma averaged 0.542 on day 1 and 0.715 on day 3, indicating that accumulation in the milk occurred with time (11). The amounts of saccharin a nursing infant could consume from milk were predicted to be much less than the usual intakes of children less than 2 years old (11).

References

1. London RS. Saccharin and aspartame: Are they safe to consume during pregnancy? J Reprod Med 1988;33:17–21.
2. Council on Scientific Affairs, American Medical Association. Saccharin:review of safety issues. JAMA 1985;254:2622–4.
3. Pitkin RM, Reynolds WA, Filer LJ Jr, Kling TG. Placental transmission and fetal distribution of saccharin. Am J Obstet Gynecol 1971;111:280–6.
4. Cohen-Addad N, Chatterjee M, Bekersky I, Blumenthal HP. In utero exposure to saccharin: a threat? Cancer Lett 1986;32:151–4.
5. Fritz H, Hess R. Prenatal development in the rat following administration of cyclamate, saccharin and sucrose. Experientia 1968;24:1140–1.
6. Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:566–7.
7. Kline J, Stein ZA, Susser M, Warburton D. Spontaneous abortion and the use of sugar substitutes. Am J Obstet Gynecol 1978;130:708–11.
8. Jensen OM, Kamby C. Intra-uterine exposure to saccharin and risk of bladder cancer in man. Int J Cancer 1982;15:507–9.
9. London RS. Letter to the editors. J Reprod Med 1988;33(8):102.
10. Nabors LO. Letter to the editors. J Reprod Med 1988;33(8):102.
11. Collins Egan P, Marx CM, Heyl PS, Popick A, Bekersky I. Saccharin excretion in mature human milk (abstract). Drug Intell Clin Pharm 1984;18:511.

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