Newborn screening for congenital adrenal hyperplasia in Cuba: Six years of experience
Highlights
► We demonstrated the validity of SUMA technology for the newborn screening of CAH. ► In Cuba, the newborn screening program has allowed the early detection of CAH. ► A screening algorithm that adjusts COV for BW improves the efficiency of the program.
Introduction
Congenital adrenal hyperplasia (CAH) represents a family of autosomal recessive endocrine disorders caused by different enzyme deficiencies affecting the adrenal steroid biosynthesis of cortisol and aldosterone, and increasing secretion of 17-hydroxyprogesterone (17OHP) and androgens. The most common form of CAH, which accounts for > 90% of classical forms, is the 21-hydroxylase deficiency [1]. The estimated worldwide incidence of classic CAH is around 1:15,000 [2].
Over the past 30 years, newborn screening programs for CAH have been established in many countries [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. The benefits of newborn screening programs for CAH include reductions in adrenal crises, life-threatening complications, and incorrect sex assignments.
In the 1980s, a technology that allowed the study of a great number of samples with the lowest possible cost was developed in Cuba. Starting from these initial efforts, the Ultra Micro Analytic System (SUMA) and the ultramicro-ELISA (UMELISA) techniques were developed. UMELISAs combine the high sensitivity of the current microELISA tests with the use of ultramicro-volumes of samples and reagents [13]. Since January 1st, 2005, a Cuban national screening program for CAH using the 17OHP Neonatal UMELISA was initiated [14]. This work shows the major results of the first 6 years of Cuban newborn CAH screening program.
Section snippets
Screening strategy
Newborn screening program for CAH is managed by the Ministry of Public Health of Cuba through its Program for Comprehensive Care for Women and Children (PAMI, Spanish acronyms) and the National Institute of Endocrinology; which coordinate the actions of the health institutions in charged for the diagnosis, confirmation, control of the cases, treatment, follow-up of patients and attention to families.
Newborn screening tests are conducted by a national laboratory network made initially up by 32
Screening program results
From January 2005 to December 2010 a total of 621,303 newborn samples were studied for CAH with a screening coverage of > 98% of total births and continued increasing progressively. Average age of sampling was 6 days with results available at 11 days of life. Thirty-nine patients with CAH were detected within the first 2 weeks of life and were classified by type and sex. Thirty-one neonates classical CAH forms (79%) were detected, 15 patients were diagnosed as simple virilizing and 16 as
Discussion
A neonatal screening program for CAH based on the detection of 17OHP on DBS allows the early diagnosis of newborns affected leading to prompt therapeutic intervention, thereby preventing morbidity and mortality. In Cuba, neonatal mass screening for CAH has been performed since 2005 when an extended Cuban National Screening Program for 5 different diseases (congenital hypothyroidism, CAH, phenylketonuria, biotinidase deficiency and galactosemia) using SUMA technology was implemented. The current
List of abbreviations
- BW
Birth-weight
- CAH
Congenital adrenal hyperplasia
- COV
Cut off value
- DBS
Dried blood on filter paper
- GA
Gestational age
- 17OHP
17-hydroxyprogesterone
- IQR
Interquartile range
- RR
Recall rate
- SUMA
Ultra Micro Analytic System
- UMELISA
Ultramicro enzyme-linked immunosorbent assay
Acknowledgment
We thank Lic. José Luis Fernandez Sierra for his help in the final language revision of the manuscript.
References (35)
- et al.
Congenital adrenal hyperplasia
Lancet
(2005) - et al.
An enzyme immunoassay for determining 17α-hydroxyprogesterone in dried blood spots on filter paper using an ultramicroanalytical system
Clin Chim Acta
(2008) - et al.
Improving the efficacy of newborn screening for congenital adrenal hyperplasia by adjusting the cut-off level of 17α-hydroxyprogesterone to gestational age
Screening
(1994) - et al.
Newborn screening for congenital adrenal hyperplasia in New Zealand
J Pediatr
(1995) - et al.
Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels
J Pediatr
(1997) - et al.
Newborn screening for congenital adrenal hyperplasia has reduced sensitivity in girls
J Pediatr
(2005) - et al.
Clinical and environmental influences on metabolic biomarkers collected for newborn screening
Clin Biochem
(2013) - et al.
Male gender predisposes to prolongation of pregnancy
Am J Obstet Gynecol
(2002) Adrenocortical function and dysfunction in the fetus and neonate
Semin Neonatol
(2004)- et al.
Congenital adrenal hyperplasia
N Engl J Med
(2003)
Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Pediatrics
Effect of gender, birth weight and gestational age on serum 17 hydroxy progesterone concentration and distribution among neonates in Saudi Arabia
Indian J Pediatr
Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia
Pediatrics
Evaluation of neonatal screening for congenital adrenal hyperplasia
Horm Res
Newborn screening in North America
J Inherit Metab Dis
Neonatal screening in Europe; the situation in 2004
J Inherit Metab Dis
Newborn screening in Latin America at the beginning of the 21st century
J Inherit Metab Dis
Cited by (15)
Newborn screening for congenital adrenal hyperplasia in New York State
2016, Molecular Genetics and Metabolism ReportsCitation Excerpt :In 2010 due to the kit antibody change and the change in cut-off levels, the referral numbers were reduced but the number of borderline cases increased. Our results indicate sex differences in mean 17-OHP concentrations as has previously been reported in Saudi Arabia, Cuba, Wisconsin and Iowa with mean levels higher in males than females [16–19]. In contrast, in Colorado female infants were reported to have higher 17-OHP values which was explained by their lower birth weights [20].
Screening threshold for congenital adrenal hyperplasia in preterm and full-term infants by an indirect method
2024, Chinese Journal of Applied Clinical PediatricsEthnic and National Differences in Congenital Adrenal Hyperplasia Incidence: A Systematic Review and Meta-Analysis
2023, Hormone Research in PaediatricsMolecular Analysis of 21-Hydroxylase Deficiency Reveals Two Novel Severe Genotypes in Affected Newborns
2021, Molecular Diagnosis and Therapy