Rarity of Congenital Adrenal Hyperplasia in Children Born Very Preterm: Possible Mechanism and Implication for Newborn Screening.

Abstract

Introduction: Screening for congenital adrenal hyperplasia (CAH) through the measurement of 17-hydroxyprogesterone on the neonatal blood spot aims to: (a) prevent neonatal deaths; (b) allow earlier identification and thereby decrease the severity of the initial salt-wasting episode; and (c) shorten the time during which a severely virilized genetic female newborn may be assigned the male sex. It is now practiced in the majority of high-income countries, although the positive predictive value of the test is very low in infants born preterm, who seem to be infrequently affected. In almost all low- and middle-income countries, it has not yet been implemented.

Methods: To determine if it is justified in such a country, we evaluated the prevalence of premature birth and the sex ratio in a cohort of 299 singleton Algerian infants diagnosed with CAH.

Results: Only 4% were born before 37 weeks of gestational age, less than the 14.3% observed in the general Algerian population. None was born before 34 weeks of gestation. The SW form of the disease was confirmed in 93 boys and 139 girls.

Conclusion: We speculate that the combination of a high production of 17-hydroxyprogesterone with a low production of cortisol by the fetus with CAH accounts for the rarity of very preterm birth in this population. We suggest that newborn screening for CAH is necessary in Algeria to equalize the sex ratio but that it could be restricted to neonates born after 32 weeks of gestation, thereby possibly improving the cost-effectiveness ratio of this intervention.