The adjustment of 17-hydroxyprogesterone cut-off values for congenital adrenal hyperplasia neonatal screening by GSP according to gestational age and age at sampling

Jiang, Xunqing; Tang, Fang; Feng, Yan; Li, Bei; Jia, Xiaoting; Tang, Chengfang; Liu, Sichi; Huang, Yi‐Zhi

doi:10.1515/jpem-2019-0140

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…Measurement of a steroid ratio, often (17OHP + androstenedione [4AD])/cortisol ([17OHP + 4AD]/cor), has shown to further improve the positive predictive value (PPV) of the screening [1,14]. In addition, the use of gestational age (GA) and birth weight-adjusted cut-offs for steroid metabolites aims to improve sensitivity and the PPV of the screening [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark: 10 Years of Experience

et al. 2022

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Introduction: Early detection of salt-wasting congenital adrenal hyperplasia (SW-CAH) is important to reduce CAH related morbidity. However, neonatal screening has shown to have a low positive predictive value (PPV), especially among preterm newborns. Here, the Danish CAH screening is evaluated by comparing incidence and morbidity of SW-CAH ten years before and after introduction of screening. Furthermore, sensitivity, specificity and PPV are determined. Methods: All newborns in Denmark born during 1999-2018 and diagnosed with SW-CAH were identified in the Danish National Patient Registry and/or at the Department of Clinical Genetics, Rigshospitalet. Newborns with a positive neonatal CAH screening were identified at Statens Serum Institut. Correct diagnosis was evaluated by medical record review. Results: A total of 65 newborns with SW-CAH were identified. The incidence of SW-CAH was 5:100,000 both before and after introduction of screening. Performance of sensitivity and specificity of the screening were 97% and 100%, respectively, and the PPV was 55% for the given period. Stratified according to gestational age, the PPV was 33% and 61% for pre -and fullterm newborns, respectively. Though not significant the proportion of newborns presenting with salt-wasting crisis decreased after introduction of screening from 29% vs. 10% (p=0.07). Discussion and Conclusion: Neonatal screening for SW-CAH has not led to an increase in the incidence of newborns diagnosed with SW-CAH. The screening algorithm has effectively identified newborns with SW-CAH. After 2009, there was a tendency towards a lower proportion of newborns with salt-wasting crisis at diagnosis. Finally, the study emphasizes the benefits of using second-tier screening as well as repeated screening of premature newborns.

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Section: Introductionmentioning

confidence: 99%

Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark: 10 Years of Experience

et al. 2022

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“…As demonstrated in an early report, median blood 17OHP concentrations in healthy term infants were greater than 100 nmol/L in cord blood, decreasing to 38 nmol/L by 12-18 h, and to 23 nmol/L by 24 h of life [47]. The implication of this data is that screening cutoffs should be adjusted to the time of collection [23]. If screening laboratories do not account for collection times, results from early sample collection (collected prior to 48 h of life) may be falsely identified as positive.…”

Section: Physiological Changes In 17ohp Concentrations After Birthmentioning

confidence: 63%

“…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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“…CAH included a group of disorders involving defects in cortisol synthesis, with the prevalence of about one in 10,000 births (17). According to previous studies, 17-OHP screening for CAH is facing challenges because of a high false-positive rate and a low positive predictive value (18)(19)(20). However, the NGS procedure for CAH is also technically challenging as the highly identical pseudogene of CYP21A2 makes it difficult to assess the accuracy of sequencing.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of expanded newborn screening for 573 genes related to severe inherited disorders in China: results from 1,127 newborns

Luo

Sun

et al. 2020

Ann Transl Med

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Background: Newborn screening (NBS) in China is mainly aimed at detecting biochemical levels of metabolites in the blood, which may generate false-positive/negative results. Current biochemical NBS includes tandem mass spectrometry (MS/MS) screening for metabolites as well as phenylalanine (Phe), thyroid-stimulating hormone (TSH), 17-α-hydroxyprogesterone (17-OHP), and glucose-6-phosphate dehydrogenase (G6PD) test. This study intended to explore whether next-generation sequencing (NGS)for dried blood spots combining with biochemical screening could improve the current screening efficiency and to investigate the carrier frequencies of mutations in causative genes related to amino acid metabolism, organic acid metabolism, and fatty acid oxidation in this cohort. Methods:We designed a panel of 573 genes related to severe inherited disorders and performed NGS in 1,127 individuals who had undergone biochemical NBS. The NGS screening results of neonates were used to compare with the biochemical results.Results: NGS screening results revealed that all the four newborns with abnormal G6PD values carried hemizygous G6PD mutations, which were consistent with the decreased G6PD enzymatic activity. The NGS results revealed an individual with compound heterozygous mutations of SLC22A5, who was biochemically negative in 2016. The MS/MS screening results in 2019 showed free carnitine deficiency, which was consistent with the genetic findings. The top five genes with the highest carrier frequencies of mutations in

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The adjustment of 17-hydroxyprogesterone cut-off values for congenital adrenal hyperplasia neonatal screening by GSP according to gestational age and age at sampling

Cited by 15 publications

References 17 publications

Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark: 10 Years of Experience

Neonatal Screening for Congenital Adrenal Hyperplasia in Denmark: 10 Years of Experience

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

A pilot study of expanded newborn screening for 573 genes related to severe inherited disorders in China: results from 1,127 newborns

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