Treatment of choice in prenatal congenital adrenal hyperplasia -
Ans-B i.e., DexamethasonePrenatal treatment of congenital adrenal hyperplasia consists of maternal administration of dexamethasone which is not degraded by the placenta and crosses into the fetal circulation.The rationale for prenatal therapy is that suppression of pituitary ACTH secretion by exogenous glucocorticoid would prevent or reduce virilization of the external genitalia of affected females. Approximately 85% of prenatally treated female infants are born with normal or slightly Virilize genitalia.This treatment is most effective in preventing abnormal genital development in affected female fetuses when it is initiated as soon as pregnancy is initiated.Very early diagnosis is required because virilization of affected female, fetuses begin as early as four weeks.Rapid genotyping of fetal cells obtained by chorionic villus sampling at 8-10 weeks of gestation appears to be the best approach but therapy must be started at the time of first missed menstrual period, well before the molecular diagnosis is available. If the treatment cannot be begun by nine weeks it should not be given at all.Congenital adrenal hyperplasia is an autosomal recessive disorder causing absent or deficient cortisol production.The most common form of congenital adrenal hyperplasia arises from mutations in "CYP21A2 " gene encoding the 21 hydroxylase enzyme.Severely affected female fetuses undergo virilization.* Treating the fetus prenatally with glucocorticoid administration to the mother has been shown to decrease or even prevent this virilization.However, the current approach to prenatal treatment means that unaffected as well as affected fetuses are exposed to dexamethasone and this treatment may have a side effect, particularly on the central nervous system.Prenatal treatment of congenital adrenal hyperplasia with dexamethasone remains controversial because to prevent ambiguous genitalia in some fetus we have to risk 8 pregnancies to corticosteroid treatment.Congenital adrenal hyperplasia is an autosomal recessive disorder. If both the parents are carrier the fetus will have one in four chance of having congenital adrenal hyperplasia.Furthermore, only half of the affected fetuses will be females hence treatment is only potentially beneficial for only one in eight fetuses. (Remember, that only female fetuses need treatment for virilization. Male fetuses do not undergo virilization).To prevent female virilization treatment must be started very early in the first trimester (essentially as soon as a pregnancy test is positive) before it is possible to determine the sex and whether or not the child is affected by congenital adrenal hyperplasia.Therefore 7 of 8 pregnancies will be treated unnecessarily to prevent 1 case of ambiguous genitalia.The diagnosis of CAH can only be made after 9-12 weeks by chorionic villus biopsy:But the treatment should begin much earlier than this as the virilization starts as soon as 4-6 weeks after gestation.Therapy must be started at the time of first missed menstrual period well before the molecular diagnosis is available.This treatment should be initiated as soon as pregnancy is recognized. If treatment cannot be begun by nine weeks of gestation, it should not be given at all.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 carrier, seven in eight infants will receive unnecessary treatment.* Since glucocorticoid treatment is associated with some adverse effect there have been objections or controversies surrounding the prenatal treatment.Corticosteroids are most often used in pregnancy to promote fetal lung maturation before impending premature delivery.But in this use betamethasone is given only for few days rather than for several weeks to months as in congenital adrenal hyperplasia.Glucocorticoids are neurotoxic in fetal and animal studies and accumulating evidence is showing mildly adverse neurodevelopmental outcomes in treated human fetuses.Therefore it does not seem logical to submit 7 of 8 fetuses to any risk whatsoever when the treatment cannot benefit them, but instead potentially benefits in 8 affected. Taken together the safety of corticosteroid has not been established and the potential risk to the mother. It seems prudent to provide prenatal dexamethasone treatment in a research setting. Treatment should only be managed by an experienced team and parents should be fully informed.
Hydrocortisone
Dexamethasone
Betamethasone
Prednisolone