In their article entitled “Fetal Cosmetology” the authors mischaracterize the anatomical ramifications of severe virilization of females with congenital adrenal hyperplasia (CAH) as requiring only “cosmetic surgeries in childhood.” In fact, in addition to clitoromegaly, the more severely virilized children have joining of the urethra and vagina into a single, common channel – the urogenital sinus. Even without doing surgery on the enlarged clitoris, surgical reconstruction to separate the urinary and reproductive tracts in childhood is necessary to prevent urinary incontinence and infections leading to renal damage as well as to allow normal urination and future sexual function.
This is not merely cosmetic surgery. And Walter Miller’s claim that this problem can be corrected in one stage when a child is six months old understates the complexity, surgical challenge, and anesthetic risk (all potentially avoidable) to a child with CAH.
Ethical issues and potential side effects to mother and fetus notwithstanding, a number of studies (two can be found here and here) have established the effectiveness of prenatal treatment for CAH using dexamethasone. In some treated neonates with CAH there is no evidence of virilization, suggesting totally successful therapy. In others there is milder masculinization than that noted in an affected sibling. (For a more detailed discussion of CAH and its treatments see Diamond DA, “Sexual Differentiation: Normal and Abnormal” in Campbell’s-Walsh Urology, Ninth Edition.) Although the population receiving prenatal dexamethasone is small, there has been sufficient use to show that it does not have the severely destructive teratogenic effects that would warrant comparison to thalidomide.
The absence of comprehensive data with which to counsel women reflects in part the real-world challenges of conducting research during pregnancy.While we agree there is insufficient scientific evidence about the risks of harm to fetuses and mothers, we also think there is insufficient scientific evidence to warrant banning its use completely. There are many drugs taken by pregnant women for which we have limited long-term data about the possible harmful effects on fetuses – antidepressants, asthma medications, and anti-epileptics, for example.
Rather than banning the use of prenatal dexamethasone, we support informing parents with a fetus at risk for CAH about the potential anatomical ramifications of the disorder, the potential benefits and risks of harm of treatment – including the likelihood of treating an unaffected fetus and data about possible neurotoxic effects – and the potential risks of no treatment, and letting pregnant women themselves weigh the benefits and risks of these alternatives for themselves and their children.
Because the number of neonates at risk for CAH at any specific hospital, clinic, or obstetrical office is very small and because we believe available data argues for a benefit to treatment in some children, we feel an appropriate model for collecting further needed data is to establish a national registry, which would enable every parent at risk of having a fetus with CAH to voluntarily enroll and researchers to track long-term outcomes of children whose mothers decided for or against treatment with prenatal dexamethasone. Such a research registry should be reviewed and monitored by institutional review boards at appropriate coordinating centers.
Clearly, new or improved prenatal technology is needed to identify affected fetuses as early as five to six weeks post conception (seven to eight weeks after a pregnant woman’s last menstrual period), when genito-urinary development begins, since standard use of prenatal tests – chorionic villus sampling at 8 to 11 weeks post conception and amniocentesis at more than 13 weeks post-conception – is too late to be of use in avoiding the unnecessary treatment of at-risk, unaffected fetuses.
David A Diamond, MD, is a professor in surgery (urology), at Harvard Medical School and a senior associate in urology at Children’s Hospital Boston. Jeffrey Ecker, MD, is an associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School and an attending perinatologist at Massachusetts General Hospital. Ingrid Holm, MD, MPH, is an assistant professor of pediatrics at Harvard Medical School and in the department of medicine and the divisions of genetics and endocrinology at Children’s Hospital Boston. Susan Kornetsky, MPH, is director of clinical research compliance at Children’s Hospital Boston. Christine Mitchell, RN, MS, MTS, is director of the Office of Ethics at Children’s Hospital Boston and associate director of clinical bioethics in the Division of Medical Ethics at Harvard Medical School. Norman Spack, MD, is an assistant professor of pediatrics at Harvard Medical School and an associate in endocrinology at Children’s Hospital Boston.