I respectfully submit this letter to strongly encourage continued dialogue in relation to newborn Congenital Adrenal Hyperplasia (CAH) screening standards in Wisconsin. I commend your newborn screening laboratory and colaborators' identification and analysis of different 17hydroxyprogesterone (17OH-p) levels in girls and boys as presented in Varness et. al.'s Newborn screening for congenital adrenal hyperplasia has reduced sensitivity in girls. However, Wisconsin's current higher-than-average 17OH-p thresholds and single-screening test policy are leaving the state's babies at risk of unnecessary death or serious physical consequences and potentially causing numerous families undue financial and emotional cost.
CARES Foundation, Inc. is a non-profit organization that provides support to individuals affected by Congenital Adrenal Hyperplasia (CAH) and their families, and I serve as its Executive Director. I am also the parent of a child with a form of CAH. I have seen the devastation that can occur when states set their 17OH-p threshold levels too high and fail to conduct second screens. I have spoken with numerous families of CAH-affected children and have listened to their stories of the trauma they and their babies have endured due to false-negative newborn screening results.
National Newborn Screening and Genetics Resource Center records as of November 2005 include 17OH-p threshold tiers for 27 states. For normal-birth-weight babies 21 of 27 states have set their cut-off at 50ng/mL or less. The average threshold for low-birth-weight babies in these states is 129ng/mL. Wisconsin is at 55ng/mL and 135ng/mL respectively.
Of these states, 11 require a second screen if the first sample was collected within 24 hours of birth, one within 36 and three within 48. Only three states (Delaware, New Mexico and Texas) require two screens no matter what. Seven "recommend" a second screen, including Wisconsin, and two do them by request only.
From this paper, it would appear Wisconsin's arguments against lowering thresholds and requiring a second screen are:
- "...[L]owering the threshold level for abnormal 17- OHP levels...would yield only marginal gains in sensitivity, with a substantial increase in the number of false-positive test results, which would increase the economic and psychological costs of evaluating infants with false-negative results."
- Wisconsin is achieving its stated goal "to prevent a life-threatening salt-wasting crisis in infants with CAH and to avoid male assignment to female infants with CAH" as evidenced by "none of the infants [in this study] with false-negative results died, had a salt-wasting crisis, or was initially assigned the wrong sex."
- Second screens are "less cost-effective" and tend to identify "primarily infants with simple virilizing CAH."
I would like to address each of these beginning with the cost of false-positive results. While it can be frustrating and confusing for a family to be mislead by a false-positive result and costly to retest an infant only to find they are unaffected by CAH, the financial, physical and emotional savings of reduced false-negative results far outweigh these costs. If detected early enough, children affected by CAH merely need simple and inexpensive medications to live a normal life. If undetected, they and their families face the possibility of severe financial, physical, and psychological costs.
It is difficult to understand how one can conclude Wisconsin has not missed any babies affected by CAH unless there is a 100% autopsy rate for infant deaths. Due to the sudden on-set of adrenal crisis generally within the first two weeks of life and various obstacles to obtaining a rapid diagnosis, undetected CAH-affected children who die often are classified as SIDS. Even this study notes that several of the false-negatives appeared "serendipitously."
Finally, CARES believes the goal of any newborn screening program should be to detect as many Classical CAH-affected infants as possible. As you know, CAH is a family of inherited disorders affecting the adrenal gland. The most common type is 21-hydroxylase deficiency. The severe form of this adrenal insufficiency, called Classical CAH, occurs in both salt-wasting and simple virilizing forms. Undetected children affected by salt-wasting CAH (SWCAH) - the focus of Wisconsin's newborn screening program - die within weeks of birth if left undiagnosed and permitted to suffer a salt-wasting crisis. Simple virilizing CAH (SVCAH) - largely ignored by this program - is not life-threatening; however, due to enzymatic impariment, both boys and girls affected by SVCAH can experience premature puberty, excessive masculinization, short stature and a variety of fertility problems. There is no reason why SVCAH-affected children should be systematically excluded from the benefits of an effective newborn screening program.
There is nothing you can do to change the lives of children already established as CAH-affected or those who never were diagnosed and died. However, there is something you can do to greatly reduce the number of Wisconsin families receiving false-negative CAH newborn screening results. On behalf of present and future CAH families of Wisconsin, I ask that you aggressively persue expanding screening for CAH to include lower 17OH-p threshold levels and a required second screen.
