Combined Gestational Age- and Birth Weight–Adjusted Cutoffs for Newborn Screening of Congenital Adrenal Hyperplasia

Pode‐Shakked, Naomi; Blau, Ayala; Pode‐Shakked, Ben; Tiosano, Dov; Weintrob, Naomi; Eyal, Ori; Zung, Amnon; Levy‐Khademi, Floris; Tenenbaum‐Rakover, Yardena; Zangen, David; Gillis, David; Pinhas‐Hamiel, Orit; Loewenthal, Neta; Vries, Liat de; Landau, Zohar; Rachmiel, Mariana; Abu-Libdeh, Abdulsalam; Eliakim, Alon; Strich, David; Koren, Ilana; German, Alina; Sack, Joseph; Almashanu, Shlomo

doi:10.1210/jc.2018-02468

Cited by 26 publications

(23 citation statements)

References 28 publications

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“…Therefore, two-tier testing may be more appropriate, particularly in populations with high birth rates and/or high rates of consanguinity. Employing LC-MS/MS as second tier test and the use of cut-off values adjusted for gestational age and birth weight are other important measures to improve PPV ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Güran¹,

Tezel²,

Çakır³

et al. 2020

Jcrpe

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Turkish Directorate of Public Health introduced the first pilot screening program for congenital adrenal hyperplasia (CAH) in four Turkish cities in 2017, and in 2018 extended the program, with a slight change in screening strategy, to fourteen cities. To evaluate the performance of the extended study and update previously reported outcomes. Methods: Retrospective, descriptive study. Neonates of ≥32 gestational weeks and ≥1500 gr birth weight from fourteen cities, born between May-December 2018, were included. Screening protocol included one sample, two-tier testing as applied in the previous pilot study. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at

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Section: Discussionmentioning

confidence: 99%

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Güran¹,

Tezel²,

Çakır³

et al. 2020

Jcrpe

View full text Add to dashboard Cite

show abstract

“…However, neonatal screening for CAH has a relatively high false positive rate, which may have delayed its general implementation [ 7 ]. Gestational age and/or birth weight related cut-off levels have been used to try to solve this problem [ 8 , 9 , 10 , 11 ]. Second tier strategies using tandem mass spectrometry measuring additional steroid metabolites and using ratios of metabolites are also used and have been shown to be useful in reducing the number of false positive cases [ 7 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Update on the Swedish Newborn Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Zetterström

Karlsson

Falhammar

et al. 2020

IJNS

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Congenital adrenal hyperplasia (CAH) was the fourth disorder added to the national Swedish neonatal screening program in 1986, and approximately 115,000 newborns are screened annually. Dried blood spot (DBS) screening with measurement of 17-hydroxyprogesterone (17OHP) is also offered to older children moving to Sweden from countries lacking a national DBS screening program. Here, we report an update on the CAH screening from January 2011 until December 2019. Results: During the study period, 1,030,409 newborns and 34,713 older children were screened. In total, 87 newborns were verified to have CAH, which gives an overall positive predictive value (PPV) of 11% and 21% for term infants. Including the five missed CAH cases identified during this period, this gives an incidence of 1:11,200 of CAH in Sweden. Among the older children, 12 of 14 recalled cases were found to be true positive for CAH. All patients were genotyped as part of the clinical follow-up and 70% of the newborns had salt wasting (SW) CAH and 92% had classic CAH (i.e., SW and simple virilizing (SV) CAH). In the group of 12 older children, none had SW CAH and two had SV CAH. Conclusion: The incidence of classic CAH is relatively high in Sweden. Early genetic confirmation with CYP21A2 genotyping has been a valuable complement to the analysis of 17OHP to predict disease severity, make treatment decisions and for the follow-up and evaluation of the screening program.

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“…17OHP is elevated in both preterm and sick newborns, and typically males have higher 17OHP concentrations than females [7,18]. These factors have lead laboratories to adjust cutoff values based upon the baby's sex, birth weight and/or gestational age [19][20][21][22][23][24], yet in general, the positive predictive value remains low (on average less than 10%) for the first-tier immunoassay performed on specimens collected within the first two days of life [25]. Lastly, there are reports of missed cases of severe SW-CAH, because measured 17OHP concentrations were below set thresholds [26], suggesting that even lower cutoffs may be needed for the first-tier assay [27].…”

Section: Newborn Screeningmentioning

confidence: 99%

Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy

Held

Bird

Heather

2020

IJNS

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Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.

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Combined Gestational Age- and Birth Weight–Adjusted Cutoffs for Newborn Screening of Congenital Adrenal Hyperplasia

Cited by 26 publications

References 28 publications

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: Outcomes of Extended Pilot Study in 241,083 Infants

Update on the Swedish Newborn Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy

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