fetal life in both sexes. Synthesis of aldosterone is also dependent on 21-hydroxylase activity. Although fetal production is impaired, it causes no prenatal effects, as the placental connection allows maternal blood to "dialyze" the fetus and maintain both electrolyte balance and blood volume. Diagnosis Since CAH is an autosomal recessive disease, most children with CAH are born to parents unaware of the risk and with no family history. Each child will have a 25% chance of being born with the disease. Classification The condition can be classified into "salt-wasting", "simple virilizing", and "nonclassical" forms. The salt-wasting and simple virilizing types are sometimes grouped together as "classical". Newborn screening Conditions justifying newborn screening for any disorder include (1) a simple test with an acceptable sensitivity and specificity, (2) a dire consequence if not diagnosed early, (3) an effective treatment if diagnosed, and (4) a frequency in the population high enough to justify the expense. In the last decade more states and countries are adopting newborn screening for salt-wasting CAH due to 21-hydroxylase deficiency, which leads to death in the first month of life if not recognized. The salt-wasting form of CAH has an incidence of 1 in 15,000 births and is potentially fatal within a month if untreated. Steroid replacement is a simple, effective treatment. However, the screening test itself is less than perfect. While the 17α-hydroxyprogesterone level is easy to measure and sensitive (rarely missing real cases), the test has a poorer specificity. Screening programs in the United States have reported that 99% of positive screens turn out to be false positives upon investigation of the infant. This is a higher rate of false positives than the screening tests for many other congenital metabolic diseases. Measurement of 17α-hydroxyprogesterone (17α-OHP) by LC-MS/MS reduces false positive rate in newborn screening in comparison to measurement by immunoassays. 17α-OHP steroid precursors and their sulphated conjugates which are present in the first two days after birth in healthy infants and longer in pre-term neonates, cross-react in immunoassays with 17α-OHP, giving falsely high 17α-OHP levels. When a positive result is detected, the infant must be referred to a pediatric endocrinologist to confirm or disprove the diagnosis. Since most infants with salt-wasting CAH become critically ill by 2 weeks of age, the evaluation must be done rapidly despite the high false positive rate. Levels of 17α-hydroxyprogesterone, androstenedione, and cortisol may play a role in screening. Additional markers