Prenatal treatment of congenital adrenal hyperplasia

in European Journal of Endocrinology
Authors:
S LajicDepartment of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden.

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A NordenstromDepartment of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden.

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EM RitzenDepartment of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden.

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A WedellDepartment of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden.

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In foetuses at risk of virilising congenital adrenal hyperplasia (CAH), prenatal treatment can be offered by administration of dexamethasone (DEX) via the mother, in order to suppress foetal adrenal androgen oversecretion and prevent genital malformations. The first treated cases were described 20 years ago, and several hundred pregnancies have been reported since. There is a consensus that the treatment effectively prevents or reduces virilisation, but opinions regarding its safety differ. Rare adverse events have been reported in treated children, but no harmful effect has been documented that can be clearly attributed to the treatment. However, few treated foetuses have been followed until adolescence. Animal studies and epidemiological data point to various adverse effects of excess glucocorticoids on the developing foetus. In order to prevent virilisation effectively in females affected with CAH, the prenatal treatment needs to be instituted in the early first trimester, before prenatal diagnosis is possible. Thus, a majority of treated foetuses will receive DEX unnecessarily.The PREDEX study was initiated in Stockholm in 1999 as an open, controlled, non-randomised, multicentre trial. Participating centres are Stockholm, Bergen, Kuopio, Warsaw, London, Lyon and Barcelona. The study has been approved by the ethics committees in each country. The purpose of PREDEX is to evaluate prospectively the prenatal treatment regarding efficacy in preventing virilisation as well as to study its safety for both mothers and treated children. Children are followed until 18 years of age and a wide range of physiological, metabolic and developmental parameters are considered. In Sweden, treatment is not offered outside the frames of the trial.

 

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