EXTENSIVE PERSONAL EXPERIENCE: Prenatal Diagnosis for Congenital Adrenal Hyperplasia in 532 Pregnancies

Abstract

Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.

Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia: does dexamethasone cause behavioural problems?

“…Girls with CAH are treated until term. Treatment safety has been reported to be acceptable, at least in the short-term perspective, based on findings of normal pre-and postnatal growth (1,(4)(5)(6), and the side effects that have been reported do not appear to follow a particular pattern (4,(6)(7)(8). Thus, the current short-term follow-up studies on humans suggest that DEX treatment does not have major teratogenic effects.…”

“…The newborn girl with virilising CAH (SVor SW) can, in the most severe cases, be mistaken for a boy due to a persistent urogenital sinus, labioscrotal fusion and clitoromegaly, leading to a traumatising experience for the family. There is a general agreement that these malformations can be reduced or prevented by prenatal treatment with the synthetic glucocorticoid (GC) dexamethasone (DEX) and, consequently, reconstructive surgery can be avoided (1)(2)(3). To be fully effective the DEX treatment has to be started in the sixth to seventh postmenstrual week and continued until the results of the prenatal diagnosis by means of a chorionic villous biopsy are available.…”

Identificación de mutaciones puntuales del gen de la 21-hidroxilasa en pacientes afectados con hiperplasia suprarrenal congénita.

“…Esta observación y su relación con formas específicas de hiperplasia suprarrenal congénita ha sido también descrito en otras poblaciones y representa un conocimiento relevante en la aplicación de predicción de fenotipo en los estudios de diagnóstico prenatal (31). El 75% de los pacientes fueron heterocigotos compuestos y el 25%, homocigotos, resultado que es comparable con lo reportado en otros estudios (14).…”

Non-classic congenital adrenal hyperplasia

“…a female infant) consideration may be given to using high dose dexamethasone suppression in early gestation, before 10 weeks gestational age [97,98], until definitive diagnosis and chromosomal sex can be obtained using chorionic villi sampling or early amniocentesis (by 10-13 weeks gestational age). However, this experimental therapy is associated with significant risk of Cushingoid features and glucose intolerance in the mother [99].…”