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First Trimester Prenatal Treatment and Molecular Genetic Diagnosis of Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)^*

PHYLLIS W. SPEISER, NICOLA LAFORGIA, KOJI KATO, JUDITH PAREIRA, RAFIYA KHAN, SOO YOUNG YANG, CHRISTOPHER WHORWOOD, PERRIN C. WHITE, SHERMAN ELIAS, ELIZABETH SCHRIOCK, ELDON SCHRIOCK, JOE LEIGH SIMPSON, MARK TASLIMI, JENNIFER NAJJAR, STEVEN MAY, GARY MILLS, CHRISTOPHER CRAWFORD and MARIA I. NEW

Department of Pediatrics, The New York Hospital-Cornell Medical Center (P.W.S., N.L., J.P., C.W., P.C.W., C.C., M.I.N.), and the Department of Immunology, Memorial Sloan-Kettering Cancer Center (K.K., R.K., S.Y.Y) New York, New York 10021
the Departments of Obstetrics/Gynecology and Pediatrics, University of Tennessee (S.E., E.S., E.S., J.L.S.) Memphis, Tennessee 38103
the Department of Obstetrics/Gynecology, University of Tennessee (M.T.) Chattanooga, Tennessee 37403
the Department of Pediatrics, Vanderbilt University (J.N.) Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Phyllis W. Speiser, M.D., Department of Pediatrics, Room N236, New York Hospital-Cornell Medical Center, 525 East 68th Street, New York, New York 10021.

Prenatal treatment of pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency was carried out in conjunction with chorionic villus sampling (CVS) in the first trimester for analysis of restriction fragment length polymorphisms. Fourteen families of a total of 49 families at risk for this disease elected to undergo both prenatal treatment and diagnosis via CVS. Dexamethasone administration to the pregnant woman was initiated at a mean gestational age of 7 weeks (range, 4–10 weeks) before testing to determine whether the fetus was affected with 21-hydroxylase deficiency, and CVS was performed at a gestational age of 8–10 weeks. Two affected female fetuses were identified by molecular genetic techniques among this group; neonatal physical examination demonstrated amelioration of the degree of genital ambiguity compared with both nonprenatally treated older sisters with 21-hydroxylase deficiency. The duration of unnecessary prenatal dexamethasone treatment for unaffected or male fetuses was substantially reduced in the CVS group compared with that in a cohort of 8 prenatally treated pregnancies in which amniocentesis was performed in the early second trimester. There were no major morbidities observed in the treated pregnancies. Postnatal confirmation of CVS diagnosis was obtained in all cases in which DNA from an affected sibling was available for comparative analysis with the DNA from chorionic villus tissue. We conclude based on these data that the benefit/risk ratio is favorable for prenatal administration of dexamethasone in pregnancies at risk for 21-hydroxylase deficiency. Treatment should be initiated during the first trimester in conjunction with diagnosis by CVS/molecular genetic techniques. Long term postnatal surveillance is recommended for all offspring of dexamethasone-treated pregnancies.

^* This work was supported by USPHS NIH Grants HD-00072, RR-47, AM-97029, and DK-37867, the Horace Goldsmith Foundation, and the Harold and Juliet Kalikow Foundation.

Present address: Highland Pediatric Clinic, 4843 C Hixson Pike, Hixson, Tennessee 37343.

Present address: 5211 Highway 153, Hixson, Tennessee 37343.

Received July 17, 1989.

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