Management Of Congenital Adrenal Hyperplasia Research Articles

Prenatal treatment of mothers with fetuses at risk for congenital adrenal hyperplasia: How relevant is it to Indian context?

Management of congenital adrenal hyperplasia (CAH) from embryonic stage to adulthood is a critical challenge. We would like to comment on some of the practical difficulties in offering prenatal treatment for CAH-affected fetuses in Indian population. For initiating the prenatal dexamethasone (DEX) treatment, all members of the family need to be informed about the risks and benefits of the treatment to the mother and the fetus as well as about the available invasive diagnostic tests to determine the gender and genotype of the fetus. Prenatal sex disclosure is not routinely practiced in India due to high female feticide rate. The treatment has to be given to both unaffected and affected female fetuses until the determination of prenatal sex. Moreover, most of our populations reside in rural areas where the antenatal care is not adequate. Prenatal DEX treatment in India outruns the risks rather than the benefits, as evident from the literature on the safety of pregnant mothers and fetuses.

Management of congenital adrenal hyperplasia in childhood

Congenital adrenal hyperplasia (CAH) can present management challenges to the pediatric clinician. Glucocorticoid replacement remains the cornerstone of treatment; however, there are new formulations and delivery mechanisms being studied. Clinicians continue to discuss the optimal treatment of patients from the prenatal stage, through infancy to adulthood. As well, the role of genetics in the clinical care of patients with CAH, and screening for complications, remain topics of discussion. This review will highlight advances made in the past year, as they pertain to the management of pediatric patients with CAH. This article covers recent studies pertaining to optimal medication regimens, including prenatal dexamethasone treatment; medication delivery; monitoring of hormonal control; and the role of genotyping and genetics in the management of children with CAH. Much remains to be learned about the optimal management of children with CAH, including fludrocortisone replacement in simple-virilizing patients, frequency of specific monitoring strategies (e.g., electrolytes, bone age), catecholamine status, stress-dosing in nonclassical adrenal hyperplasia, and early screening for complications or metabolic sequelae. Further randomized and prospective studies are needed to address these issues.

Management of CAH during pregnancy

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. In the past, pregnancy was considered to be unlikely for women with CAH, particularly the classical forms. The purpose of this review is to provide current information regarding the pathophysiology of CAH, factors relevant for female and male fertility, and recommendations for management during pregnancy. Individuals with CAH, both female and male, have reduced fertility. For women, chronic anovulation, elevated progestin levels, and aberrant endometrial implantation have been identified as reasons for the subfertility. Testicular adrenal rest tumors, oligospermia, and hypogonadotropic hypogonadism are frequently associated with subfertility in men with all forms of CAH. Adequate suppression of progesterone appears to be an essential aspect of preconception management for women. Most importantly, treatment needs to be individualized. Awareness of these factors and appropriate therapeutic interventions can lead to successful outcome defined as a healthy live born infant.

Clinical outcomes in the management of congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of disorders affecting adrenal steroid synthesis. The most common form, 21-hydroxylase deficiency, leads to decreased production of cortisol and aldosterone with increased androgen secretion. In classic CAH glucocorticoid treatment can be life-saving, and provides symptom control, but must be given in an unphysiological manner with the risk of negative long-term outcomes. A late diagnosis or a severe phenotype or genotype has also a negative impact. These factors can result in impaired quality of life (QoL), increased cardiometabolic risk, short stature, osteoporosis and fractures, benign tumors, decreased fertility, and vocal problems. The prognosis has improved during the last decades, thanks to better clinical management and nowadays the most affected patients seem to have a good QoL. Very few patients above the age of 60 years have, however, been studied. Classifying patients according to genotype may give additional useful clinical information. The introduction of neonatal CAH screening may enhance long-term results. Monitoring of different risk factors and negative consequences should be done regularly in an attempt to improve clinical outcomes further.

Bilateral simultaneous laparoscopic adrenalectomy for congenital adrenal hyperplasia: Initial experience

Objective Congenital adrenal hyperplasia (CAH) is an uncommon syndrome which represents a therapeutic challenge. We analyzed the role of bilateral simultaneous laparoscopic adrenalectomy in the management of CAH. Material and methods: Between October 2004 and September 2006, three female patients underwent bilateral simultaneous laparoscopic adrenalectomy for CAH. Data were retrospectively collected. Variables analyzed were persistence of CAH clinical signs, variations in 17 OH progesterone level and corticoid medication, operative time, median blood loss, postoperative pain, hospital stay, and body image perception after surgery. Results Median age was 16.3 years. Complete regression of virilization signs, acne and hyperpigmentation was achieved in one case. The other two cases showed partial regression of signs. Levels of 17 OH progesterone reached normal parameters in all cases. Steroids doses were lowered and given only for replacement purposes. Mean operative time was 125, 65 and 60 min for whole, right and left procedure, respectively. Median blood loss remained under 50 ml in all cases and there were no complications. Median postoperative pain level was 5 according to visual analog pain scale. Median hospital stay was 4 days. Conclusion Bilateral simultaneous laparoscopic adrenalectomy shows all the advantages of minimally invasive surgery, and appears a viable alternative to medical management, which is not exempt from complications.

Alternative Strategies for the Treatment of Classical Congenital Adrenal Hyperplasia: Pitfalls and Promises

Despite decades of different treatment algorithms, the management of congenital adrenal hyperplasia (CAH) remains clinically challenging. This is due to the inherent difficulty of suppressing adrenal androgen production using near physiological dosing of glucocorticoids (GC). As a result, alternating cycles of androgen versus GC excess can occur and may lead to short stature, obesity, virilization, and alterations in puberty. Novel therapeutic alternatives, including new and more physiological means of GC delivery, inhibitors at the level of CRH or ACTH secretion and/or action, as well as “rescue strategies”, such as GnRH analogs, anti-androgens, aromatase inhibitors, and estrogen receptor blockers, are available; many of these agents, however, still require active investigation in CAH. Bilateral adrenalectomy is effective but it is also still an experimental approach. Gene therapy and stem cells, to provide functional adrenal cortical tissue, are at preclinical stage but provide exciting avenues for a potential cure for CAH.

Congenital Adrenal Hyperplasia: The Challenges of Management in a Developing Country

Objective: The management of congenital adrenal hyperplasia (CAH) is challenging, particularly in developing countries. The objective of this study is to report the challenges and outcome of management of this pathology at an institution in Nigeria. Patients and Methods: All the children that were diagnosed with CAH at the University of Benin Teaching Hospital, Benin City, Nigeria, between January 2002 and December 2007 were included in this retrospective study. The parameters studied were: age, sex, mode of presentation, family history of similar lesions, fi ndings on examinations and investigations, treatment given, challenges and outcome. The available parents/caregivers were interviewed in order to document their socioeconomic status, place of residence, level of education and level of awareness about CAH. The data obtained were analyzed using SPSS and presented as count, frequency and percentage, while continuous data were expressed as mean ± standard deviation. Results: In total, 27 children aged between 2 and 15 (mean 8 ± 2.4) years were treated. Twentyfour of them were females and 3 males with a male-to-female ratio of 1:8. Delayed presentation, which was infl uenced by cultural beliefs and lack of awareness, was very common and none of the cases was diagnosed under 2 years of age. Genital manifestation was the reason for seeking medical consultation in 23 (85%) patients, while the 3 males (11%) and one female (4%) presented due to precocious puberty. All the females were mistakenly raised as males despite obvious deformity of the phallus. Establishing an accurate diagnosis was a major challenge due to the lack of facilities and manpower required, and a combination of clinical, radiological and biochemical laboratory investigations plus/minus mini-laparotomy was used. Although surgical and steroid replacement therapy was satisfactory, gender re-assignment was very challenging and required a multidisciplinary approach, counseling and relocation of the affected families. Conclusion: Management was diffi cult mainly due to late presentation, and there is an obvious need for a public information campaign in our country in order to increase the awareness of CAH in order to avoid wrong gender assignment in neonates. Keywords : Congenital adrenal hyperplasia, management, gender African Journal Of Urology Vol.14 (3) 2007: pp. 138-142

Outcome of bilateral adrenalectomy in congenital adrenal hyperplasia: one unit’s experience

The use of bilateral adrenalectomy in the management of congenital adrenal hyperplasia (CAH) is controversial. We set out to review the outcome of 5 cases of CAH who have undergone adrenalectomy in our unit. A retrospective case note review and subject interview of the experience of adrenalectomy in the setting of a tertiary adult CAH clinic. Subjects who had undergone adrenalectomy were reviewed at a routine clinic visit with particular reference to clinical and biochemical outcomes after adrenalectomy. Two subjects underwent surgery for the sole indication of desire for fertility with successful outcome and without subsequent adrenal crises. Three women suffered from the common clinical management problem of unsuppressible hyperandrogenism and worsening obesity. Whilst the outcome of improved appearance and weight loss was achieved in these subjects, all three experienced significant complications including pigmentation and acute episodes of adrenal insufficiency. We present a mean follow-up of 4.2 patient years and conclude that this procedure may be suitable for selected women with CAH. Outcomes for those pursuing fertility were positive; however, complications were noted in those women for whom the procedure was performed for symptom control. Accepting that the number of subjects is small, it is clear that more data are required before widely recommending this procedure.

Diagnosis and management of congenital adrenal hyperplasia

Congenital adrenal hyperplasia is the name applied to a class of autosomal recessive disorders resulting from deficiency of one of five enzymes necessary for cortisol synthesis by the adrenal cortex. Congenital adrenal hyperplasia is most often attributable to steroid 21-hydroxylase deficiency, accounting for more than 90% of cases. This discussion will be limited to the most common form of the disease, highlighting methods of diagnostic screening and challenges in disease management.

Congenital adrenal hyperplasia in adults: a review of medical, surgical and psychological issues

Our knowledge of the experience of adults with congenital adrenal hyperplasia (CAH) as they pass through life is only now emerging. In this review we gather medical, surgical and psychological literature pertaining to adults with CAH and consider this alongside practical experience gained from a dedicated adult CAH clinic. There is increasing awareness for the need for multidisciplinary teams who have knowledge of CAH particularly with respect to gynaecological surgery and clinical psychology for women and testicular function in men. Routine management of CAH comprises adjustment of glucocorticoid and mineralocorticoid treatment according to individual needs balancing biochemical markers, compliance and long term risks. Bone density is one such long term concern and is not greatly reduced in most individuals with CAH. More recently, attention has turned to cardiovascular risk factors and catecholamine deficiency in adults with CAH. Women with CAH require access to an experienced gynaecologist, specialised pregnancy care and psychosexual support. The very low fertility rates for women with CAH previously reported appear to be improving with time. Men with CAH are often lost to follow up and therefore miss out on surveillance for hypogonadism either through the effect of adrenal rests of from suppression of gonadotrophins resulting in a high prevalence of oligospermia.

Timing and Type of Glucocorticoid Replacement in Adult Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is one of the commonest inherited diseases. Treatment during childhood is directed towards obtaining normal growth. There is an extensive literature on management of CAH during childhood but little published on how patients should be treated as adults. CAH results in increased adrenocorticotropic hormone levels driving the adrenal to produce cortisol and thereby excessive cortisol precursors which are predominantly androgenic. In normal individuals there is a marked circadian rhythm in cortisol release with the lowest levels occurring shortly after midnight and rising between 02.00 and 03.00 h to peak at around 06.00–08.00 h after waking. The treatment of choice for children with CAH is hydrocortisone three times daily. There is no consensus on treating adults. A recent survey by the UK Society for Endocrinology showed that hydrocortisone was the most popular steroid, followed by dexamethasone and then prednisolone. Sixty percent of respondents used a reverse circadian pattern of glucocorticoid treatment and only 16% used a dose based on weight or surface area. In a recent study we demonstrated that the most important variable determining hydrocortisone bioavailability is weight and we advocated a weight-related dosing regimen monitored using a nomogram for serum cortisol.

Management of 21-hydroxylase deficiency congenital adrenal hyperplasia: A survey of Canadian paediatric endocrinologists

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Many issues in the management of CAH in children still remain unresolved. To assess how children with CAH are treated in Canada. Fifty-nine paediatric endocrinologists and postgraduate trainees from across Canada took part in a survey that evaluated four areas of CAH management: type and dose of glucocorticoid therapy, current use of alternative therapies, monitoring of care, and approach/attitude to prenatal diagnosis and treatment of CAH. The present survey demonstrated that there is general agreement among paediatric endocrinologists in Canada regarding the management of patients with CAH, which includes very little use of newer antiandrogen therapies. The goal remains to be the optimization of currently available therapy to ensure normal growth and sexual maturation without any evidence of glucocorticoid excess or deficiency. Prenatal diagnosis and management is widely, but infrequently, used.

Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Congenital adrenal hyperplasias (CAH) are inherited defects of cortisol biosynthesis. More than 90% of CAH are caused by 21-hydroxylase deficiency (21-OHD), found in 1:10 000 to 1:15 000 live births. Females with 'classical' 21-OHD, being exposed to excess androgens prenatally, are born with virilized external genitalia. Potentially lethal adrenal insufficiency is characteristic of two-thirds to three-quarters of patients with the classical salt wasting (SW) form of 21-OHD. Non-SW 21-OHD may be diagnosed on genital ambiguity in affected females, and/or later on the occurrence of androgen excess in both sexes. Non-classical 21-OHD, detected in > or =1:100 of certain populations, may present as precocious pubarche in children or polycystic ovarian syndrome in young women. 21-OHD is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombination between CYP21 and the closely linked CYP21P pseudogene. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disorder. This close association between genotype and phenotype makes it possible to predict clinical outcome in affected subjects. The risk of SW and prenatal virilization can be estimated, and overtreatment can be avoided in mildly affected cases. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment, but additional therapies are being developed. A first trimester prenatal diagnosis should be proposed in families in whom molecular studies have been performed previously. The state of heterozygotism can be predicted by hormonal testing and confirmed by molecular studies. Prenatal diagnosis by direct mutation detection in previously genotyped families permits prenatal treatment of affected females in order to avoid or minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before SW crises develop, reducing mortality in this disorder.

Congenital adrenal hyperplasia: transitional care

Congenital adrenal hyperplasia (CAH) is a life-long disorder which poses management problems that are age- and sex-specific. The condition merits an organised, multi-disciplinary transitional care format similar to the kind that is now well established for Turner's syndrome in many centres. In the eyes of the paediatrician, achieving optimal growth is the primary target of CAH management during infancy and childhood. Fixation on this objective can be to the detriment of the patient because it may result in failure to appreciate the significance of metabolic disturbances that occur in later childhood, particularly in females, and which may be the progenitor of chronic problems with obesity, insulin resistance and infertility in adult life. Similarly, the care of the adult patient with CAH comprises more than just prescribing steroid replacement for primary adrenal insufficiency. The transition period between childhood and adulthood is an opportune time for review of the various management options and to assess the efficacy of steroid replacement, to consider alternative novel treatment modalities and to apply a checklist to the multi-faceted aspects of the medical, surgical and psychological needs of the patient.

Management of Congenital Adrenal Hyperplasia: Results of the ESPE Questionnaire

The management of children and adolescents with congenital adrenal hyperplasia (CAH) remains difficult. To assess the current European practice in diagnosis and management of CAH, an ESPE (European Society for Paediatric Endocrinology) survey was circulated in 2000/2001. The questionnaire was answered by 34% of ESPE members, representing 125 institutions which cared for 6,553 CAH patients. Paediatric endocrinologists, surgeons, gynaecologists, geneticists, and psychologists are involved in the immediate care of the CAH neonate and his family. 44% of centres take part in neonatal screening programmes. In families at risk, prenatal dexamethasone therapy is started at a median gestational age of 6 weeks in a median dose of 20 µg/kg/day. 53% reported maternal adverse events, 8% observed adverse fetal events. Regarding feminizing surgery, 33% reported simultaneous clitoric reduction and vaginoplasty during infancy. However, clitoridectomy is still reported by 13% of centres, and vaginal dilatations have been performed by 27%. Although 71% of female CAH patients with psychosexual problems, only 17% undertake routine psychodiagnostics and counselling. Hydrocortisone is the substance used for the treatment of CAH during growth in 84%; the median dose (mg/m²/day) is 17.5 in infants, 15 in children and adolescents, and 13.75 in adults. The glucocorticoid dose is increased two- to sixfold during intercurrent stress. Mineralocorticoid is administered in cases of clinically manifest salt wasting and of elevated plasma renin activity, to decrease high glucocorticoid doses, or according to genotype. All participating ESPE members feel the need for further improvement in prenatal diagnosis and treatment, compliance during puberty, screening programmes, psychological aspects, and corrective surgery.

Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle European countries.

Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders, some patients are not identified, or may even die, in an acute salt-losing crisis. In a retrospective study covering the last 30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5 Middle European countries, and the mortality rate in diagnosed patients and their siblings during childhood; we also attempted to estimate how many patients are not diagnosed clinically each year. Basic and follow-up clinical data and the family histories of 484 patients with classical forms of CAH diagnosed between 1969 and 1998 were collected and recorded in 5 Middle European countries. The sex-ratio, time elapsing before diagnosis, and mortality among siblings and patients were calculated, and the number of undiagnosed patients was estimated. We found significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic CAH patients, and the percentage of diagnosed boys did not increase with time; 64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple virilizing (SV) form, of the disease. The diagnosis of CAH was established significantly later in males than in females in both forms [SW: 26 vs. 13 days (median), P < 0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the general population was significantly lower than in either siblings (1.8% vs. 7.0%; P < 0.0001) or in SW (2.29% vs. 11.3%; P < 0.0001). According to our calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to 5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries investigated. Both clinical detection and treatment of CAH patients, at least in males, were insufficient in the five Middle European countries examined during the last 30 yr. Neonatal mass screening and/or greater awareness of the medical community are discussed as ways of improving the efficacy of CAH management. Our experience may be applicable to other countries with similar health care systems.

Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

The management of congenital adrenal hyperplasia due to 21-hydroxylase (CYP21) deficiency requires glucocorticoid substitution with oral hydrocortisone given twice or thrice daily. In paediatric practice little is known of the bioavailability of oral hydrocortisone tablets used in these patients. The aim of this study was to assess the bioavailability of oral hydrocortisone and to evaluate current replacement therapy in the light of cortisol pharmacokinetic properties. We determined the bioavailability of hydrocortisone following oral and intravenous administration in sixteen (median age: 10.9 years, range: 6.0-18.4 years) adequately controlled CYP21 deficient patients. Serum total cortisol concentrations were measured at 20-min intervals for 24 h while patients were on oral substitution therapy, and at 10-min intervals for 6 h following an intravenous bolus of hydrocortisone in a dose of 15 mg/m(2) body surface area. The area under the serum total cortisol concentration versus time curve (AUC) following oral and intravenous administration of hydrocortisone was calculated using the trapezoid method. The bioavailability was estimated by dividing the corrected for dose AUC after oral hydrocortisone administration by the corrected for dose AUC after the intravenous hydrocortisone administration and was exemplified as a percentage. After oral administration of hydrocortisone in the morning, median serum total cortisol concentrations reached a peak of 729.5 nmol/l (range: 492-2520 nmol/l) at 1.2 h (range: 0.3-3.3 h) and declined monoexponentially thereafter to reach undetectable concentrations 7 h (range: 5-12 h) after administration. Following administration of the evening hydrocortisone dose, median peak cortisol concentration of 499 nmol/l (range: 333-736 nmol/l) was attained also at 1.2 h (range: 0.3-3.0 h) and subsequently declined gradually, reaching undetectable concentrations at 9 h (5-12 h) after administration of the oral dose. After the intravenous hydrocortisone bolus a median peak serum total cortisol concentration of 1930 nmol/l (range: 1124-2700 nmol/l) was observed at 10 min (range: 10-20 min). Serum cortisol concentrations fell rapidly and reached undetectable levels 6 h after the hydrocortisone bolus. The absolute bioavailability of oral hydrocortisone in the morning was 94.2% (90% confidence interval (CI): 82.8-105.5%) whereas the apparent bioavailability in the evening was estimated to be 128.0% (90% CI: 119.0-138.0%). We conclude that the bioavailability of oral hydrocortisone is high and may result in supraphysiological cortisol concentrations within 1-2 h after administration of high doses. The even higher bioavailability in the evening, estimated using as reference the data derived from the intravenous administration of hydrocortisone bolus in the morning, is likely to reflect a decrease in the hydrocortisone clearance in the evening. Decisions on the schedule and frequency of administration in patients with congenital adrenal hyperplasia should be based on the knowledge of the bioavailability and other pharmacokinetic parameters of the hydrocortisone formulations currently available.

Congenital adrenal hyperplasia: from genetics and biochemistry to clinical practice, part 2.

Congenital adrenal hyperplasia (CAH) refers to a group of genetic disorders with defects in the synthesis of cortisol. The synthesis of other steroids such as mineralocorticoids and adrenal/ gonadal sex steroids may also be affected. The clinical presentation of the various forms of CAH depend on the following: (1) the affected enzyme, (2) the residual enzymatic activity, (3) the physiologic consequences of deficiencies of the end-products and excess of precursors. The second part of this two-part review discusses the diagnosis and the management of CAH. Although methods for the diagnosis of CAH have not changed over the past few years, new therapeutic approaches are changing the management of CAH. In particular, new drugs and new drug combinations are being tested and old dogmas are being questioned. Early diagnosis, careful discussion with family members of newborns with CAH during the early decision-making process, and close management will decrease the mortality rate and improve the long-term psychological/physical outcome of these children.

Congenital adrenal hyperplasia: epidemiology, management and practical drug treatment.

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a common disorder, and is characterised by a defect in cortisol biosynthesis with or without a defect in aldosterone synthesis and androgen excess. The classic form, also known as the severe form, occurs in 1:15,000 births worldwide, while the nonclassic or mild form occurs in approximately 1:1,000 births worldwide and is much more common (up to 1:20) in certain ethnic groups. In classic 21-hydroxylase deficiency, glucocorticoids are given in doses sufficient to suppress adrenal androgen secretion, and mineralocorticoids are given to normalise electrolytes and plasma renin activity. The management of CAH may be complicated by iatrogenic Cushing's syndrome, inadequately treated hyperandrogenism, or both. Prenatal treatment may decrease virilisation of the affected female foetus, but the efficacy and safety of treating CAH prenatally remains to be fully defined. Close clinical monitoring of growth and development is essential to optimise treatment outcome. New treatment approaches are currently under investigation in the most severely affected patients, while nonclassic CAH does not always require treatment.

DEXAMETHASONE TREATMENT OF CONGENITAL ADRENAL HYPERPLASIA IN UTERO: AN EXPERIMENTAL THERAPY OF UNPROVEN SAFETY

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common cause of genital virilization in female infants resulting from inappropriate fetal adrenal androgen secretion. Some investigators have advocated treating pregnant women who are at risk for carrying a CAH fetus with dexamethasone to suppress fetal adrenal androgen synthesis. Experience to date shows that this treatment can be effective in ameliorating the genital virilization in female fetuses. However, the doses used are supraphysiological, the mechanism of dexamethasone action in the fetus is unclear and no long-term followup studies have been done. To be effective the treatment would need to be started by week 6 of gestation but the genetic diagnosis cannot be made until week 12. If the mother has had a previous CAH child, only 1 in 4 pregnancies will be affected and only the female fetuses stand to benefit from treatment, thus, 7 of 8 fetuses will be treated needlessly. In view of these and other concerns, the prenatal treatment of CAH remains an experimental therapy and, hence, must only be done with fully informed consent in controlled prospective trials approved by human experimentation committees at centers that see enough of these patients to collect meaningful data.