STREPTOMYCIN IN PREGNANCY: EFFECT ON THE FOETAL EAR.

Abstract

The treatment of active tuberculosis during pregnancy is complicated by the problem of the safety of the drugs employed. In order to prevent the emergence of drug-resistant organisms it is customary during the initial stages to give streptomycin as well as isoniazid and p-aminosalicylic acid, and, while the mother is of course subject to the risk of ototoxic damage due to streptomycin, it is not entirely clear how far this risk extends to the foetus. Certainly streptomycin does cross the placenta : this was established in 1945 by Woltz and Wiley and indepen dently by Heilman et al. (1945). Subsequent work (Bernhard et al, 1950 ; Riskaer et al., 1952 ; Charles, 1954) confirmed that, although the effectiveness of the placental barrier varies, streptomycin and dihydrostreptomycin (Jacobsen, 1953) are present in foetal blood in up to 50% of maternal concentrations. The effect of these drugs on the foetus was studied experiment ally by Riskser et al., using guinea-pigs ; no disturbance of auditory or vestibular function was apparent. Watson and Stow (1948) were the first to examine this ques tion clinically ; they found no obvious abnormality in two children born after high maternal doses of streptomycin during pregnancy. Later reports agreed, and Kreibich (1954) was able to collect from the literature 35 cases in which children at risk seemed to be unaffected. Since 1950, however, several case reports have appeared of deaf children born to mothers treated with streptomycin for tuberculosis. Leroux (1950) described the case of a child aged 2 with deafness (and normal caloric responses) whose mother had received 30 g. of streptomycin in the last month of pregnancy. Bolletti and Croatto (1958) reported the case of a girl of 5 with severe deafness and impaired vestibular function, the maternal dose of streptomycin having been 1 g. daily for 85 days prior to delivery. Kern (1962) described the case of a 6-year-old girl with severe deafness in the left ear and total deafness in the right. A caloric test evoked very little response. In this case the mother had been treated with 20 g. of dihydrostreptomycin in the first four months of pregnancy. Finally, in a study of the causes of deafness in 300 children, Robinson and Cambon (1964) dis covered two further children with severe deafness and absent caloric responses. The first mother fiad been given 1 g. of streptomycin twice weekly for eight weeks in the first trimester, and the second a similar dosage for the last four months of pregnancy. Apart from these isolated cases there have been three papers describing the otological findings in small groups of children at risk. Rebattu et al. (1960) found two cases of high tone loss among six children they examined, and in one the caloric tests were abnormal. Lenzi and Ancona (1962) studied 10 children aged 7-10 years and their mothers. Audiograms showed that three of the children were deaf ; all the mothers were normal. Grande and Vespa (1963) examined nine mothers and their 14 children, then aged 7-11 years. In this instance all the mothers had received dihydrostreptomycin, the dose ranging from 5 to 80 g. Four mothers and three children had perceptive deaf ness ; five more children had mixed deafness. Vestibular function was studied with galvanic and caloric tests, of which no details were given ; all the children were stated to be normal. These three series suggest a relatively high incidence of deaf ness (possibly related in the last one to the use of dihydro streptomycin, which is more apt than streptomycin itself to damage cochlear function), and it is therefore surprising that so few children with deafness caused in this way have been reported. The present investigation was undertaken in an attempt to reassess the incidence of deafness in children at risk. Furthermore, in theory one would expect labyrinthine rather than cQchlear damage to be the commoner finding after the use of streptomycin, and accordingly vestibular function was examined in detail.