Tetracycline and Congenital Limb Abnormalities

Carter, M. P.; Wilson, Francis N.

doi:10.1136/bmj.2.5301.407-c

Cited by 47 publications

(4 citation statements)

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“…There appears to -be direct relationship between the stability of a tetracycline and its concentration in the foetal skeleton as demonstrated by fluorescence; this is probably related to a longer persistence in the foetal blood of more stable tetracyclines during the time of bone formation. Although it was not possible to find true malformations in our experiments with rabbits and rats, there is ample evidence in the literature on the influence of tetracyclines in delaying growth and causing malformations (Filippi & Mela, 1957;Bevelander, Goldberg & Nakahara, 1960;Bevelander, Nakahara & Rolle, 1960;Carter & Wilson, 1962;Cohlan, Bevelander & Bross, 1962;Cohlan, Bevelander & Tiamsic, 1963).…”

Section: Discussionmentioning

confidence: 76%

Possible Relationship Between Tetracycline Stability and Effect on Foetal Skeleton

Tubaro¹

1964

British Journal of Pharmacology and Chemotherapy

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A possible relationship between stability of a tetracycline and persistence in the foetal skeleton is discussed; it seems that the greater the stability of a tetracycline, the more it may interfere with bone-forming processes. Therefore, assuming that limited instability does not impair antibiotic potency in vivo, the use of a low-stability tetracycline seems to be a safer form of treatment in order to avoid undesired effects on the foetal skeleton.In recent years the occurrence of skeletal malformations in animal and human foetuses after administration of tetracycline has frequently been reported (Bevelander, Nakahara & Rolle, 1959;Bevelander & Goss, 1962;Wallman & Hilton, 1962;Hurley & Tuchmann-Duplessis, 1963.;Smith & Chapman, 1963); this occurrence is probably due to the typical avidity of tetracycline for metal cations acting as a prosthetic group in bone-forming enzymes (Eagle & Saz, 1955; Shils, 1962).All the investigations on teratogenicity or abnormal bone calcifications have until now been carried out with tetracycline itself and not with other members of this group; moreover, in the case of tetracycline, only the relationship between abnormal effect and dosage or length of treatment has been investigated. In the course of work on the monosodium salt of N-methylol-chlortetracycline (chlormethylenecycline), experiments on developing chick embryos were carried out with the object of evaluating possible variations of its chelating effect compared with the actions of other tetracyclines. METHODSChick embryos of an inbred hybrid strain were used 8 days after the onset of hatching; single 1 mg doses of demethylchlortetracycline, tetracycline, chlortetracycline and the monosodium salt of chlormethylenecycline were dissolved in 0.1 ml. and were injected under sterile conditions into the yolk sac of the embryo. Demethylchlortetracycline, tetracycline and chlortetracycline were used as the hydrochlorides. All doses refer to the bases.Eggs were sealed with sterile cellulose tape and placed in an incubator at 38 C; embryos and their sagittal sections (prepared by the same method as for rabbits; see below) were examined on the 16th day after the onset of hatching and were viewed under ultra-violet light.Groups of five female rabbits were injected intravenously from the 10th to 20th day of pregnancy with 10 mg/kg/day of the tetracyclines. The neonates were then rapidly frozen with a dry-ice mixture of solid carbon dioxide and acetone and whole-body sagittal sections were cut using a 1213 Leitz freezing microtome equipped with a 90 mm Jung type C knife.

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Section: Discussionmentioning

confidence: 76%

Possible Relationship Between Tetracycline Stability and Effect on Foetal Skeleton

Tubaro¹

1964

British Journal of Pharmacology and Chemotherapy

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“…In tissue culture studies an inhibition of osteogenesis has been observed in the presence of tetracyclines (18). Furthermore, the occurrence of congenital limb malformations due to tetracyclines has been discussed (19). Severe adverse effects, such as lethal fatty liver degeneration, were reported in pregnant women undergoing tetracycline therapy (often after a high dosage) (20,21).…”

Section: Vancomycinmentioning

confidence: 98%

Antibiotics in pregnancy: Toxicity and teratogenicity

Knothe

Dette

1985

Infection

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“…These individuals mistakenly assumed that the same rigorous methods that were necessary to identify the first effect are no longer necessary, once the agent has been identified as a reproductive toxicant. There are a number of case reports of children with LRDs or other malformations who were born to mothers exposed to tetracycline during their pregnancy [Batagol, 1980;Chow and Jewesson, 1985;Carter, 1962;Carter and Wilson, 1962;Corcoran and Castles, 1977;Filippi, 1969;Morrissey et al, 1986;Medical Letter, 1985;Pomerance and Yaffe, 1973;Schwarz, 19811. Epidemiological and animal studies have not supported this allegation, yet these reports were used as a basis for birth defect litigation.…”

mentioning

confidence: 99%

Congenital malformation case reports: The editor's and reviewer's dilemma

Brent

1993

Am. J. Med. Genet.

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Tetracycline and Congenital Limb Abnormalities

Cited by 47 publications

References 0 publications

Possible Relationship Between Tetracycline Stability and Effect on Foetal Skeleton

Possible Relationship Between Tetracycline Stability and Effect on Foetal Skeleton

Antibiotics in pregnancy: Toxicity and teratogenicity

Congenital malformation case reports: The editor's and reviewer's dilemma

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