Melissa
17.10.2007, 15:01
PRENATAL THERAPY — Prenatal diagnosis of CYP21A2 deficiency was originally undertaken to provide parents with information regarding the disease status of the fetus. Prenatal diagnosis also has been performed to decide whether to initiate prenatal therapy. However, because prenatal therapy may have adverse effects, the decision to treat should be made in consultation with a highly experienced team, and preferably in a research setting. (See "Overview of classic congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency", section on Prenatal diagnosis).
The rationale for prenatal therapy is that suppression of fetal pituitary ACTH secretion by exogenous glucocorticoid would prevent or reduce virilization of the external genitalia of affected females. Very early diagnosis is required because virilization of affected female fetuses begins as early as four weeks. Rapid genotyping of fetal cells obtained by chorionic villus sampling at 8 to 10 weeks of gestation appears to be the best approach, but therapy must be started at the time of the first missed menstrual period, well before the molecular diagnosis is available.
Prenatal treatment consists of maternal administration of dexamethasone, which is not degraded by the placenta and crosses into the fetal circulation. This treatment is most effective in preventing abnormal genital development in affected female fetuses when it is initiated as soon as pregnancy is recognized [4-8]. If treatment cannot be begun by nine weeks of gestation, it should not be given at all [9,10]. Approximately 85 percent of prenatally treated female infants are born with normal or slightly virilized genitalia [11]. Treatment failures have been attributed to early cessation of therapy, late start of therapy, nonadherence, suboptimum dosing, or differences in dexamethasone metabolism. Treatment is discontinued if genetic testing reveals a male fetus or an unaffected female. Since the risk of having an affected female fetus is one in eight when both parents are known carriers, seven in eight fetuses will receive treatment unnecessarily. Adverse effects for the mother include increased appetite, early and excessive weight gain, edema, striae, and signs and symptoms of Cushing's syndrome [10,12,13].
UpToDate Online
The rationale for prenatal therapy is that suppression of fetal pituitary ACTH secretion by exogenous glucocorticoid would prevent or reduce virilization of the external genitalia of affected females. Very early diagnosis is required because virilization of affected female fetuses begins as early as four weeks. Rapid genotyping of fetal cells obtained by chorionic villus sampling at 8 to 10 weeks of gestation appears to be the best approach, but therapy must be started at the time of the first missed menstrual period, well before the molecular diagnosis is available.
Prenatal treatment consists of maternal administration of dexamethasone, which is not degraded by the placenta and crosses into the fetal circulation. This treatment is most effective in preventing abnormal genital development in affected female fetuses when it is initiated as soon as pregnancy is recognized [4-8]. If treatment cannot be begun by nine weeks of gestation, it should not be given at all [9,10]. Approximately 85 percent of prenatally treated female infants are born with normal or slightly virilized genitalia [11]. Treatment failures have been attributed to early cessation of therapy, late start of therapy, nonadherence, suboptimum dosing, or differences in dexamethasone metabolism. Treatment is discontinued if genetic testing reveals a male fetus or an unaffected female. Since the risk of having an affected female fetus is one in eight when both parents are known carriers, seven in eight fetuses will receive treatment unnecessarily. Adverse effects for the mother include increased appetite, early and excessive weight gain, edema, striae, and signs and symptoms of Cushing's syndrome [10,12,13].
UpToDate Online