Screening for CAH Will Save Girls' Lives, Too

February 27, 2013

A new study indicates that routine screening of newborns for congenital adrenal hyperplasia (CAH) — the most common adrenal disorder in children — does improve detection of the most lethal form of this condition among both sexes, something that had not previously been appreciated.

Recognition of severe CAH is usually possible in girls just by looking at them, because they present with virilized genitalia, lead author Sebastian Gidlöf, MD, from Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News. But boys with CAH often appear normal, with no genital malformations; they are discharged home, where they subsequently develop a salt crisis that can result in severe neurological damage or death.

Dr. Gidlöf and colleagues were surprised to find, however, that "contrary to current belief," girls with CAH were missed clinically and that screening improved detection of females with CAH as well as boys, thereby saving more lives than previously thought. They report their findings online February 26 in Lancet Diabetes & Endocrinology.

The results are important, he said, because although most developed countries and, increasingly, a number of developing nations already screen for CAH, there are some notable exceptions, including the United Kingdom and Australia.

In an accompanying comment, Bridget Wilcken, MD, from Sydney Children's Hospitals Network and University of Sydney, Australia, says: "Evidently, both male and female babies die undiagnosed, and not, as previously thought, only male babies. There is little doubt that screening for this disorder fulfills the essential criteria for screening — it is, after all, a potentially lethal disorder."

Rich Data Set Provided by 100 Years of Swedish Stats

CAH is a group of disorders, the most common type being 21-hydroxylase deficiency, associated with low cortisol and aldosterone production and a concurrent increase in androgen production. It affects around 1 in 10,000 to 15,000 live births, and clinical presentation includes potentially fatal salt-wasting crises, female genital virilization, and premature pubarche.

Dr. Gidlöf explained why some countries have taken the decision not to screen: "It is more difficult to screen for CAH than other diseases because there is an enormous rate of false positives, primarily among premature infants and those with other diseases, such as infections, who can be wrongly flagged as having the disorder."

But this new research should change that opinion, he said, because it shows that lives can be lost by not screening. He also pointed out that screening programs can be modified to make some allowances for the false-positive rate, half of which occurs among extremely premature babies.

For example, in Sweden, they do not immediately flag a premature child as having CAH, even if he or she tests positive, he explained. Since that child is usually being kept in the neonatal ward anyway, further investigations can be performed to confirm or refute the diagnosis.

In their study, he and his colleagues retrospectively analyzed all known cases of CAH in Sweden over 100 years, between 1910 and 2011, and examined the impact of medical developments over time.

They identified 606 patients with the disorder born between 1915 and 2011, with the genotype known for 81% of cases.

They show an increase in diagnosed cases during the 1960s and 1970s, following the discovery of the first effective treatment for CAH in 1950. And after the introduction of newborn screening in 1986, the proportion of severe, salt-wasting CAH cases diagnosed increased significantly, and the female-to-male ratio in these patients was close to 1.

Around 16% of diagnosed patients born after the start of the screening program were not identified by screening, but most of these (38/43 cases) were late-onset nonclassical cases, a milder form of the disease.

In her comment, Dr. Wilcken says this Swedish study "underlines what can be learned from long-term follow-up, good record keeping, and registers. This type of activity should not only be encouraged but also funded if we are to make best use of our accumulated experience." However, she also notes that publication of more detailed data from existing screening programs "would be welcome."

Lancet Diabetes Endocrinol. Published online February 26, 2013.