ESPE Abstracts

Prenatal treatment of CAH has been employed since the mid 1980’s, but long-term evaluation of this experimental treatment is scarce. In utero replacement with dexamethasone suppresses the fetal adrenal and reduces the androgens that virilise the female CAH fetus. The CAH girls are thus born with normal external genitalia and avoid early genital surgery. There is however an ethical dilemma, since the treatment with DEX has to be initiated early in gestation before genetic testing is possible and seven out of eight fetuses are thus treated during early gestation without any benefit of the treatment per se. Accumulating evidence tells us that the hormonal and nutritional milieu in utero predisposes the child to a range of diseases later in adult life. Whether prenatal DEX therapy as used in the treatment of CAH has any adverse effects on the treated fetus has been the subject of debate during the last decade. Excess levels of glucocorticoids given to experimental animals during fetal life have shown both short- and long-term consequences.

In Sweden, prenatal treatment of CAH has been administered within the frameworks of a clinical study since 1999. The aim of the study is to evaluate treatment efficacy and to identify potential side-effects in the pregnant woman, the fetus and the growing child until adult age. Longitudinal growth, metabolic status and neuropsychological outcome in conjunction with structural and functional effects on the developing brain are evaluated. Fetal programming effects at a molecular level are also addressed. The importance of continued long-term follow-up of treated cases is emphasized by previous studies from our group indicating a negative effect on working memory in children exposed to DEX during the first trimester. These first reports has led us to halt further prenatal treatment of CAH in Sweden (since 2011) until we know more about the long-term outcome of this experimental therapy.