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- What is the rationale behind prenatal therapy in CAH?
The aims of prenatal therapy for CAH is to prevent the virilization of female fetus,
reduce the need for genital reconstruction surgery, and minimize adverse psycho-
logical distress associated with genital ambiguity. This is accomplished by admin-
istering dexamethasone to the mother as soon as the pregnancy is confi rmed.
Dexamethasone is used for prenatal therapy as it is not metabolized by placental
11 β-hydroxy steroid dehydrogenase type 2(11β-HSD2) and, hence, freely crosses
placental barrier, whereas other glucocorticoids like prednisolone and hydrocorti-
sone are readily metabolized by placental 11β-HSD2. Dexamethasone inhibits
fetal hypothalamo–pituitary–adrenocortical axis and thereby suppresses fetal
adrenal androgen production and consequently prevents fetal virilization.- When to initiate dexamethasone as prenatal therapy for CAH?
Treatment with dexamethasone should be initiated as soon as pregnancy is con-
fi rmed as exposure of female embryo to adrenal androgens between 7 and
12 weeks of intrauterine life results in virilization of the urogenital sinus and
consequent genital ambiguity. Dexamethasone is administered at a dose of 20 μg/
Kg/day in divided doses with a maximum dose of 1.5 mg/day, and the preconcep-
tional weight is used for calculation of the dose. After genetic analysis by chori-
onic villous sampling at 10–12 weeks, the need for further continuation of
dexamethasone can be reconsidered. In a male fetus and unaffected female fetus,
it is discontinued, while in an affected female fetus, dexamethasone is continued.
Maternal urinary estriol may be used to monitor adequacy of therapy (DHEA and
DHEAS are converted to estriol in fetal zone of adrenal cortex). Estimation of
17(OH)P is not useful for prenatal diagnosis or monitoring of therapy.- Why is prenatal therapy for CAH not recommended?
In a woman with a child having CAH, the probability of having another child
with CAH in the subsequent pregnancy is one in four (and that of having a
female child with CAH is one in eight) as CAH is an autosomal recessive dis-
order. Hence, to prevent genital ambiguity in one female child, seven children
need to be treated unnecessarily. The effi cacy of prenatal dexamethasone ther-
apy is only 80–85 %. In addition, prenatal dexamethasone therapy is associated
with adverse fetal and maternal outcomes. Prenatal therapy results in exposure
of fetus to very high levels of glucocorticoids (approximately 60 times greater
than levels in a normal fetus). The fetal risks associated with dexamethasone
therapy include intrauterine growth retardation, orofacial congenital malforma-
tions, impaired verbal working memory in childhood, and, possibly, future risk
of cardiovascular events. The maternal risks include weight gain, edema, and,
possibly, higher incidence of hypertension and hyperglycemia. Hence, prenatal
dexamethasone therapy is still considered as experimental.10 Congenital Adrenal Hyperplasia