Drugs in Breast Milk
Dr Carl Muchnick of Torrance, California writes: "In the March 1981 issue of PIR (2:279, 1981), in his discussion of drugs in breast milk, Smith indicates that, `The risk to dental enamel and bone growth from exposure to the tetracyclines is sufficient to contraindicate the use of breast milk which predictably contains 50% of the concentrations of the drug measured in maternal serum.' However, one of Smith's references (Med Lett Drugs Ther 21:21, 1979) states: `Tetracyclines, which can discolor developing teeth in infants and children, are bound by the calcium in milk and are probably not absorbed by the nursing infant.' Also, tetracyclines are not felt to be contraindicated by various authors as summarized in White and White (Vet Hum Toxicol 22 (suppl 1):31, 1980). Inasmuch as the tetracyclines are often prescribed (rightly or wrongly), many nursing mothers are potentially involved. I would suggest, therefore, that a review of this statement be made and a clarification be made in Pediatrics in Review. I would also note the fact that doxycycline is less bound by calcium in milk and can be given with food, possibly making it an exception. However, if it is less well bound by calcium in milk does that also suggest it would not cause tooth staining? Until this question is answered, it would seem prudent to use another tetracycline if this class of drug is necessary for a nursing mother."
Dr Smith replys: "I wish to thank Dr Muchnick for calling attention to conflicting statements concerning the potential risk to the developing teeth of infants exposed to tetracyclines in breast milk. Few data exist concerning serum concentrations in infants consuming breast milk in which concentrations of the drugs are known to approximate 50% to 70% of levels in maternal serum. Posner Prigot and Konicoff (Antibiotic Annual 1954-1955, p 594) were unable to demonstrate significant antibiotic activity in the sera of five neonates who were breast-fed by women receiving oral tetracycline hydrochloride.
Despite the close similarities in the structure of the tetracyclines, there are significant differences in their rate and degree of absorption, metabolism, excretion, lipid solubility, and calcium binding. Considerable data exist to show that aluminum hydroxide, milk, or a combination of first generation tetracyclines with calcium phosphate are deterrents to absorption resulting in lower plasma concentrations. After a single 250-mg dose of tetracycline in combination with calcium phosphate, serum levels at three hours (7.5 µg/ml) are one half to one fourth the levels achieved with a combination of tetracycline and citric acid in adult patients (Boger and Gavin: N Engl J Med 261:827, 1959). The mechanisms responsible for decreased absorption appear to be chelation of calcium by the drug as well as an increase in gastric pH. Major differences exist, however, in the tissue distribution of the second generation tetracyclines, doxycycline and minocycline, related largely to their lipid solubility and minimal if any interference in absorption from ingestion of food. Measurable levels of doxycycline in multiple tissues such as female reproductive organs, kidney, and gallbladder greatly exceed concentrations in serum. Levels of minocycline in bile are 30 times higher than simultaneous levels in serum; this contributes to prolonging the half-life through reabsorption. The drug concentrates well in bones, teeth, and thyroid (Cunha, Comer, and Jonas: Med Clin North Am 66:293, 1982).
After a single dose of a tetracycline, the drug can be detected for months in areas of new bone formation. Unlike deposition of the drug in bone resulting in the formation of a tetracycline-calcium-orthophosphate complex, there is no active turnover of mineral elements in teeth. The hallmark retention of tetracycline in enamel and dentin forming at the time of ingestion of the drug is permanent. The primary teeth are most vulnerable to staining in the last trimester of pregnancy and in the early weeks of infancy. The problem is more than a cosmetic one as tetracyclines inhibit the normal process of calcification and may render the tooth more susceptible to decay. The degree of effect appears to be dose related.
I suspect that the declining usage of tetracyclines by pediatricians over the past ten to 15 years has resulted in decreased awareness on the part of many residents and young physicians regarding minor staining of teeth in children. The epidemic assault on enamel and dentin in the 1950s and 1960s has perhaps elevated the bias of some of us against the use of tetracyclines in young children. As recently as 1973, Stewart (Br Med J 3:320, 1973) reported the presence of tetracyclines in 70% of primary molars extracted from 505 children aged 3 to 5 years.
In view of the paucity of data concerning the bioavailability of various drugs in the class of tetracyclines in breast milk, it would seem prudent to discourage their use in women who are nursing their infants if safer and more effective antibiotics are available. On the other hand, I would be reassuring to parents if inadvertent exposure occurred over a relatively short period of time.
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