medwireNews: The Swedish neonatal screening programme for congenital adrenal hyperplasia (CAH), based on blood spot determination of 17-hydroxy progesterone (17-OHP), successfully detected all clinically classified salt-wasting cases of the condition during a 26-year period, researchers report.

The findings, which include data on 99.8% of infants born in Sweden between 1986 and 2011, contradict fears that screening for CAH misses cases and results in a high recall rate. The recall rate (all infants recalled due to an above-threshold result) was just 0.03% in full-term infants and 0.57% in preterm infants.

The recall rate changed during the study, because of changes made to the 17-OHP assay methodology that altered sensitivity and therefore the recall rate. Thresholds for a positive result were adjusted to account for this.

Of 2,737,932 Swedish infants, 274 had CAH, of whom 231 had a positive screening test, giving a sensitivity of 84.3% for all forms of CAH, with no difference between girls and boys.

The researchers, led by Sebastian Gidlöf (Karolinska Institutet, Stockholm, Sweden), note that this sensitivity is markedly lower than that in previous studies with shorter follow-up periods. This is to be expected, they say, “because the true sensitivity of milder forms of CAH can only be evaluated when enough time has passed to allow diagnosis of late-onset cases.”

However, they stress that the primary aim of the screening programme is to reduce mortality arising from salt loss in infancy, and in this respect, it was highly effective, as none of the 43 missed cases experienced salt loss.

All of these missed cases were genetically verified to have CAH. Three had genotypes usually associated with salt wasting. Two of these cases were boys born in the second year of the screening programme, and both had 17-OHP levels that would have been classified as positive in subsequent years. The other case was a girl who had levels below the cutoff and was identified at the age of 8 years because of other, milder symptoms.

Two infants with confirmed CAH died of known causes, and a further 39 infants with above-threshold 17-OHP levels died before recall, of causes unknown to the researchers; 19 of these infants were born before 28 weeks’ gestation.

In an editorial accompanying the study in JAMA Pediatrics, Beth Tarini (University of Michigan, Ann Arbor, USA) highlights the importance of time in revealing the benefits of screening, saying the findings challenge the idea that screening for CAH is a “lost cause”, and also demonstrate the value of genotyping to reduce false-negative results.

However, she cautions: “While DNA may help identify missed cases, it cannot reliably predict disease severity in CAH.”

By Eleanor McDermid, Senior medwireNews Reporter

JAMA Pediatr 2014; 6: 515–516, 567–574

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