Hirvikoski T, Nordenstrom A, Wedell A, Ritzen M, Lajic S. J Clin Endocrinol Metab. 2012 Mar 30

DOI: 10.3410/f.717747955.793302809

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Summary 

The practice of prescribing dexamethasone (DEX) to pregnant women at risk for carrying a female fetus affected with 21-hydroxylase deficiency has, in recent years, become very controversial {1}. The treatment is prescribed to reduce or eliminate the masculinization of the genitalia of XX-affected fetuses. The authors of this commentary, Swedish clinicians and investigators of the Karolinska Institute and University Hospital, summarize the evidence suggesting a risk to somatic health and neurocognitive development of prenatally exposed offspring.

Clinical practice guidelines view prenatal therapy as experimental and, if pursued, treatment protocols must be evaluated by institutional review boards, and then only when there exists a network of collaborating sites sufficient to yield a sufficiently large number of patients to allow for valid statements regarding the risk and benefits to mothers and patients {2,3}. Yet leaders in the pediatric endocrine community have labeled the treatment ‘safe’ and have promoted its use {4}.

Women with at-risk pregnancies and treated with DEX have been recruited from several European countries into a prospective, nonrandomized, multicenter trial; long-term follow-up data for both treated mothers and their offspring were collected. These authors, representing Sweden’s participation in the clinical trial, state that their findings of possible adverse effects on health (including the experiences of the mothers during pregnancy) and on the neurocognitive and behavioral outcomes of the offspring (both congenital adrenal hyperplasia (CAH)-affected and unaffected) have led them to suspend further recruitment of Swedish patients to the prospective study of prenatal DEX treatment. Further, they admonish the global practice of treating fetuses outside of clinical trials and without a systematic follow-up.

There are currently two practice guidelines {1,2} regarding the clinical management of congenital adrenal hyperplasia that include statements regarding the experimental status of prenatal DEX treatment. These guidelines should be scrupulously followed.

References  

1. Prenatal Treatment of Congenital Adrenal Hyperplasia-Not Standard of Care.
Witchel SF, Miller WL J Genet Couns. 2012 May 26
PMID: 22639328 DOI: 10.1007/s10897-012-9508-8

2. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline.
Speiser PW, Azziz R, Baskin LS, Ghizzoni L, …, Oberfield SE, Ritzen M, White PC, Endocrine Society J Clin Endocrinol Metab. 2010 Sep; 95(9): 4133-60
PMID: 20823466 DOI: 10.1210/jc.2009-2631