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Newborn screening for congenital adrenal hyperplasia has reduced sensitivity in girls
Todd S Varness1, David B Allen, Gary L Hoffman
1Department of Pediatrics, University of Wisconsin Children's Hospital, Madison, Wisconsin 53792-4108, USA.
Insights
Newborn screening for 21-hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH) is less sensitive in females. Female infants with false-negative results may show genital masculinization or salt-wasting.
Area of Science:
- Endocrinology
- Genetics
- Neonatal screening
Background:
- Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OH-D-CAH) is a group of genetic disorders.
- Newborn screening aims to detect 21-OH-D-CAH early to prevent salt-wasting crises and sex misassignment.
Purpose of the Study:
- To identify Wisconsin-born infants with 21-OH-D-CAH missed by newborn screening.
- To compare screening 17-hydroxyprogesterone (17-OHP) levels between male and female infants.
Main Methods:
- Analysis of false-negative newborn screening results for 21-OH-D-CAH in Wisconsin (2000-2003).
- Comparison of screening 17-OHP levels between male (n=119,842) and female (n=114,951) infants.
Main Results:
- Six of seven female infants with false-negative results had genital masculinization; four of eight had salt-wasting.
- Mean screening 17-OHP levels were significantly higher in males (17.5 ng/mL) than females (15.4 ng/mL).
- Screening sensitivity was 60% for females versus 80% for males.
Conclusions:
- Significant differences in mean 17-OHP levels exist between male and female infants.
- Female infants represent the majority of false-negative screening results for 21-OH-D-CAH.
- Newborn screening effectively prevents salt-wasting crises and sex misassignment, despite lower sensitivity in females.
Objectives:
To characterize Wisconsin-born infants with 21-hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH) who were not identified by the newborn screening for 21-OH-D-CAH, and to examine male and female screening 17-hydroxyprogesterone (17-OHP) levels.
Study Design:
Information on infants with false-negative results was gathered. Results of the Wisconsin newborn screening for 21-OH-D-CAH from January 1, 2000, to June 30, 2003, were analyzed to detect possible differences between male (n=119,842) and female (n=114,951) infants.
Results:
Six of 7 female infants with false-negative results had genital masculinization, and 4 of 8 infants with false-negative results had laboratory evidence of salt-wasting. None died, had a salt-wasting crisis, or was assigned the wrong sex. A significant difference in the mean 17-OHP levels between male (17.5 ng/mL) and female (15.4 ng/mL) infants (P <.0001) was detected. The sensitivity of newborn screening for female infants was 60%, compared with 80% for male infants.
Conclusions:
Male and female infants have significantly different mean 17-OHP levels on newborn screening, and female infants comprise most of the infants with false-negative results. Although health professionals should not assume that newborn screening for 21-OH-D-CAH is a means of identifying all affected infants, the primary goals of newborn screening for CAH (prevention of salt-wasting crises and sex misassignment) are fulfilled.
