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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The Congenital Adrenal Hyperplasias &#40;CAHs&#41; comprise a group of autosomal recessive disorders due to defects in adrenal steroidogenesis&#46; The most common is 21-hydroxylase deficiency due to mutations in the 21-hydroxylase &#40;<span class="elsevierStyleItalic">CYP21A2</span>&#41; gene&#46; The clinical spectrum ranges from life-threatening adrenal insufficiency to minimal symptoms depending on the specific <span class="elsevierStyleItalic">CYP21A2</span> mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> The clinical phenotype generally reflects the functional activity of the mildest mutation&#46; The prevalence of the classical forms&#44; salt-losing and simple virilizing&#44; differs among populations ranging from approximately 1 in 6000 in India to 1 in 19&#44;000 in Japan&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> The prevalence of non-classic or mild CAH is higher and was reported to be 1 in 2000 among Caucasians in the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">One goal of pediatrics is prevention of disease as exemplified by vaccine development&#46; Another area for prevention is the development of programs to screen and detect newborn infants for whom early intervention is beneficial&#46; For the pediatric endocrinologist&#44; Newborn Screening &#40;NBS&#41; programs for congenital hypothyroidism provide a model in which early intervention prevents poor outcomes&#46; For CAH&#44; the high risk for morbidity and mortality in the classical forms led to the development of a microfilter paper 17-OHP assay in 1977&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> Subsequently&#44; NBS protocols for CAH based on 17-OHP assays were established in over 40 countries&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Considerations prior to the establishment of a screening program include burden of the disorder&#44; knowledge of disease prevalence&#44; sensitivity and specificity of the screening test&#44; and ethical considerations regarding privacy and informed consent&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a> NBS programs are obligated to develop reliable methods to collect filter paper blood spot specimens from all newborn infants&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> The specimens need to be collected and processed within a specific timeframe&#46; The intra-assay and inter-assay coefficients of variation for the laboratory test need to be low&#46; And&#44; finally&#44; a system to locate and inform the parents and appropriate physician&#40;s&#41; is essential to an effective NBS program&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">For CAH&#44; the goal has been to identify infants with salt-losing and simple virilizing forms to prevent the morbidity and mortality due to acute adrenal insufficiency and to recognize affected females&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> NBS for CAH may also identify individuals with non-classic CAH&#46; These individuals may have minimal symptoms and never need hormone replacement therapy&#46; For the families&#44; knowledge of a genetic diagnosis may generate years of anxiety due to the uncertainty regarding development of symptoms&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Hence&#44; a challenge for CAH screening is to assure maximum sensitivity &#40;proportion of positive tests among all individuals with the condition&#41;&#44; maximum positive predictive value &#40;proportion of true positive tests among all tests&#41;&#44; and maximum specificity &#40;proportion of negative tests among all unaffected individuals&#41;&#46; Why is this such an obstacle for NBS for CAH&#63; To achieve nearly 100&#37; sensitivity&#44; the cut-point for 17-hydroxyprogesterone &#40;17-OHP&#41; recall is set such that approximately 1&#37; of all tests are reported as positive&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> At birth&#44; 17-OHP concentrations are high and decline over the first 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h of life&#46; Early specimen collection can thus lead to a false positive result&#46; False positive results &#40;elevated 17-OHP values&#41; can occur in preterm&#44; heterozygous&#44; and stressed infants&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> Some 17-OHP immunoassays cross-react with other steroids such as 17-hydroxypregnenolone sulfate and 15&#946;-hydroxylated compounds leading to false positive results&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> Most 17-OHP assays are performed with commercial kits that may vary due to seasonal temperature fluctuations and unforeseen manufacturer kit changes&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a> False positive results generate anxiety and costs inherent in follow-up evaluation to exclude the diagnosis of CAH&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> False negative results can occur&#44; generally more commonly in girls than in boys&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> Maternal treatment with glucocorticoids can also lead to false negative results&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">These challenges have led to development of strategies designed to improve the positive predictive value&#46; In the cross-sectional study by Kopacek et al&#46;&#44; their goals were to describe the results of a CAH newborn screening embedded in a public health program in Southern Brazil to assess the clinical features of infants identified through this program&#44; and to ascertain the usefulness of <span class="elsevierStyleItalic">CYP21A2</span> genetic testing in the NBS protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> During the two years of this study&#44; a total of 217&#44;965 samples were obtained from 3rd to 40th postnatal days&#46; A time-resolved immunofluorescence assay was used to measure 17-OHP concentrations in dried blood spots&#46; To minimize the false positive results&#44; Kopacek et al&#46; chose to utilize cut-points for four birth-weight tiers stratified by both Brazilian and international experience&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">14&#44;15</span></a> Repeat samples were obtained generally by 3 weeks of age for infants with elevated 17-OHP values or when mothers had used a corticosteroid late in pregnancy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">To assess the value of a second-tier molecular test&#44; the authors performed 17-OHP determinations and <span class="elsevierStyleItalic">CYP21A2</span> genetic testing on the second sample&#46; They utilized a SNaPshot assay to detect 12 common <span class="elsevierStyleItalic">CYP21A2</span> mutations and Multiplex Ligation-dependent Probe Amplification &#40;MLPA&#41; assay to detect rearrangements&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> Elevated 17-OHP values for birth weight cut points were detected in 147 infants&#46; Of these 147 infants&#44; 15 cases were confirmed to have classical CAH&#46; As would be anticipated&#44; infants found to have classical CAH had the highest 17-OHP concentrations at both timepoints&#46; Of the 15 patients found to have classical CAH&#44; all were identified by NBS prior to clinical diagnosis&#44; thus confirming the benefits of the NBS program&#46; Of the remaining 132 positive 17-OHP screening results&#44; the second-tier genetic testing revealed that 7 infants had non-classical CAH&#44; 14 were heterozygotic carriers&#44; and 96 had false positive results&#46; In this situation&#44; knowledge of the specific diagnosis was able to direct appropriate management&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">K&#246;sel et al&#46; also tested a two-tiered approach using <span class="elsevierStyleItalic">CYP21A2</span> molecular testing for samples with elevated 17-OHP values and concluded that despite the slightly higher cost&#44; this testing paradigm could reduce the need for second samples and prevent parental anxiety&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> However&#44; molecular genetic analysis can be complicated because <span class="elsevierStyleItalic">CYP21A2</span> is located in a complex genetic locus in close physical proximity to a highly homologous nonfunctional pseudogene &#40;<span class="elsevierStyleItalic">CYP21A1P</span>&#41;&#46; Most <span class="elsevierStyleItalic">CYP21A2</span> mutations associated with CAH comprise normal <span class="elsevierStyleItalic">CYP21A1P</span> sequence and represent recombination &#40;gene conversion&#41; events between <span class="elsevierStyleItalic">CYP21A2</span> and <span class="elsevierStyleItalic">CYP21A1P</span>&#46; Three neighboring genes&#44; serine&#47;threonine kinase &#40;RP&#41;&#44; complement C4&#44; and Tenascin &#40;TNX&#41;&#44; map to this locus&#46; These four genes form a unit known as the RCCX module&#44; which can be deleted or duplicated&#46; In addition to this copy number variation&#44; the high sequence homology between the functional <span class="elsevierStyleItalic">CYP21A2</span> gene and its nonfunctional pseudogene <span class="elsevierStyleItalic">CYP21A1P</span> complicates the genetic testing&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a> Discriminating deleterious mutations from Variants of Unknown Significance &#40;VUS&#41; discovered by whole genome and exome sequencing may be problematic&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> In some instances&#44; multiple laboratory methods and parental genotyping are necessary to accurately determine a child&#39;s genotype&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Collection of a second blood sample is being used to improve NBS performance parameters&#46; Currently&#44; approximately 22&#37; of American infants are routinely screened a second time&#59; this has improved detection of infants with simple virilizing and NCAH&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> Other paradigms involve use of cut-points based on gestational age&#44; collecting a second sample for 17-OHP immunoassay&#44; liquid chromatography followed by tandem mass spectrometry &#40;LC-MS&#47;MS&#41;&#44; determination of 21-deoxycortisol concentrations&#44; or hormone ratios such as 17-OHP&#47;11-deoxycortisol ratio&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">8&#44;22&#44;23</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Reflection on the details of this study can provide insight and additional perspectives&#46; Two aspects of this study warrant additional comments&#58; &#40;1&#41; maternal use of glucocorticoids and &#40;2&#41; characterization of the IVS2-13A&#47;C&#62;T variant&#46; Some mothers were taking glucocorticoids &#40;GC&#41; prior to delivery&#46; The indications for GC use and type of GC were not described&#46; Did mothers take GC for prenatal treatment to prevent genital virilization for presumably affected infants&#44; for threatened preterm labor&#44; or for another reason&#63;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The authors reported a novel variant&#44; IVS2-13A&#47;C&#62;T&#44; in two individuals&#46; These patients were labeled as being heterozygous carriers&#46; The <span class="elsevierStyleItalic">CYP21A2</span> mutation&#44; IVS2-13A&#47;C&#62;G&#44; involves the same nucleotide and was the most commonly identified mutation in this cohort&#46; The A&#47;C&#62;G mutation creates a novel upstream splice acceptor site resulting in aberrant splicing of intron 2&#44; retention of 19 intronic nucleotides&#44; and a downstream premature termination codon&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> However&#44; the possibility that the A&#47;C&#62;T variant represents a benign variant or VUS has not been addressed&#46; Functional characterization using in vitro expression studies or in silico analysis utilizing bioinformatics prediction software could be used to characterize the functional significance of this intronic variant&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Early detection&#44; confirmation of diagnosis&#44; and treatment are beneficial for individuals with salt-losing and simple virilizing forms of CAH&#46; Pediatricians&#44; family physicians&#44; pediatric endocrinologists&#44; obstetricians&#44; and neonatologists need to be knowledgeable regarding local NBS programs and understand the current limitations of screening for CAH&#46; The future holds promise as the methodology to achieve improved positive predictive values for NBS for CAH evolves&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The author declare no conflicts of interest&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Witchel SF&#46; Newborn screening for congenital adrenal hyperplasia&#58; beyond 17-hydroxyprogesterone concentrations&#46; J Pediatr &#40;Rio J&#41;&#46; 2019&#59;95&#58;257&#8211;9&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">See paper by Kopacek et al&#46; in pages 282&#8211;90&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:24 [
            0 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;F&#46; Witchel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pediatr Adolesc Gynecol"
                        "fecha" => "2017"
                        "volumen" => "30"
                        "paginaInicial" => "520"
                        "paginaFinal" => "534"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Newborn screening for congenital adrenal hyperplasia in India&#58; what do we need to watch out for&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Kishore Kumar"
                            1 => "H&#46; Das"
                            2 => "P&#46; Kini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s13224-015-0712-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Obstet Gynaecol India"
                        "fecha" => "2016"
                        "volumen" => "66"
                        "paginaInicial" => "415"
                        "paginaFinal" => "419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27821980"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Revisiting the prevalence of nonclassic congenital adrenal hyperplasia in US Ashkenazi Jews and Caucasians"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Hannah-Shmouni"
                            1 => "R&#46; Morissette"
                            2 => "N&#46; Sinaii"
                            3 => "M&#46; Elman"
                            4 => "T&#46;R&#46; Prezant"
                            5 => "W&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2017"
                        "volumen" => "19"
                        "paginaInicial" => "1276"
                        "paginaFinal" => "1279"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microfilter paper method for 17 alpha-hydroxyprogesterone radioimmunoassay&#58; its application for rapid screening for congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Pang"
                            1 => "J&#46; Hotchkiss"
                            2 => "A&#46;L&#46; Drash"
                            3 => "L&#46;S&#46; Levine"
                            4 => "M&#46;I&#46; New"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem-45-5-1003"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "1977"
                        "volumen" => "45"
                        "paginaInicial" => "1003"
                        "paginaFinal" => "1008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/925125"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population screening for genetic disorders in the 21st century&#58; evidence&#44; economics&#44; and ethics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46;D&#46; Grosse"
                            1 => "W&#46;H&#46; Rogowski"
                            2 => "L&#46;F&#46; Ross"
                            3 => "M&#46;C&#46; Cornel"
                            4 => "W&#46;J&#46; Dondorp"
                            5 => "M&#46;J&#46; Khoury"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000226594"
                      "Revista" => array:6 [
                        "tituloSerie" => "Public Health Genomics"
                        "fecha" => "2010"
                        "volumen" => "13"
                        "paginaInicial" => "106"
                        "paginaFinal" => "115"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19556749"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Newborn screening&#58; a complex system that requires a culture of safety"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "E&#46;R&#46; McCabe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgme.2014.03.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab"
                        "fecha" => "2014"
                        "volumen" => "113"
                        "paginaInicial" => "6"
                        "paginaFinal" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24726176"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nationwide neonatal screening for congenital adrenal hyperplasia in Sweden&#58; a 26-year longitudinal prospective population-based study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Gidl&#246;f"
                            1 => "A&#46; Wedell"
                            2 => "C&#46; Guthenberg"
                            3 => "U&#46; von D&#246;beln"
                            4 => "A&#46; Nordenstr&#246;m"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamapediatrics.2013.5321"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Pediatr"
                        "fecha" => "2014"
                        "volumen" => "168"
                        "paginaInicial" => "567"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24733564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal screening for congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;C&#46; White"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrendo.2009.148"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Endocrinol"
                        "fecha" => "2009"
                        "volumen" => "5"
                        "paginaInicial" => "490"
                        "paginaFinal" => "498"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19690561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "17-Hydroxyprogesterone in premature infants as a marker of intrauterine stress"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Ersch"
                            1 => "E&#46; Beinder"
                            2 => "T&#46; Stallmach"
                            3 => "H&#46;U&#46; Bucher"
                            4 => "T&#46; Torresani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/JPM.2008.013"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Perinat Med"
                        "fecha" => "2008"
                        "volumen" => "36"
                        "paginaInicial" => "157"
                        "paginaFinal" => "160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18211251"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The influence of seasonality and manufacturer kit lot changes on 17&#945;-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Pearce"
                            1 => "E&#46; Dauerer"
                            2 => "A&#46;G&#46; DiRienzo"
                            3 => "M&#46; Caggana"
                            4 => "N&#46;P&#46; Tavakoli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Pediatr"
                        "fecha" => "2017"
                        "volumen" => "176"
                        "paginaInicial" => "121"
                        "paginaFinal" => "129"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of false-positive newborn screening results on families&#58; a qualitative study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;L&#46; Schmidt"
                            1 => "K&#46; Castellanos-Brown"
                            2 => "S&#46; Childress"
                            3 => "N&#46; Bonhomme"
                            4 => "J&#46;S&#46; Oktay"
                            5 => "S&#46;F&#46; Terry"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/gim.2011.5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2012"
                        "volumen" => "14"
                        "paginaInicial" => "76"
                        "paginaFinal" => "80"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22237434"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Newborn screening for congenital adrenal hyperplasia in New York State"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Pearce"
                            1 => "L&#46; DeMartino"
                            2 => "R&#46; McMahon"
                            3 => "R&#46; Hamel"
                            4 => "B&#46; Maloney"
                            5 => "D&#46;M&#46; Stansfield"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgmr.2016.02.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab Rep"
                        "fecha" => "2016"
                        "volumen" => "7"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27331001"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Kopacek"
                            1 => "M&#46;J&#46; Prado"
                            2 => "C&#46;M&#46; da Silva"
                            3 => "S&#46;M&#46; de Castro"
                            4 => "L&#46;A&#46; Beltr&#227;o"
                            5 => "P&#46;R&#46; Vargas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pediatr &#40;Rio J&#41;"
                        "fecha" => "2019"
                        "volumen" => "95"
                        "paginaInicial" => "282"
                        "paginaFinal" => "290"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;Y&#46; Hayashi"
                            1 => "D&#46;F&#46; Carvalho"
                            2 => "M&#46;C&#46; de Miranda"
                            3 => "C&#46; Faure"
                            4 => "C&#46; Vallejos"
                            5 => "V&#46;N&#46; Brito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Endocrinol &#40;Oxf&#41;"
                        "fecha" => "2017"
                        "volumen" => "86"
                        "paginaInicial" => "480"
                        "paginaFinal" => "487"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Screening for congenital adrenal hyperplasia&#58; adjustment of 17-hydroxyprogesterone cut-off values to both age and birth weight markedly improves the predictive value"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
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                        "link" => array:1 [
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                    0 => array:2 [
                      "titulo" => "Rapid second-tier molecular genetic analysis for congenital adrenal hyperplasia attributable to steroid 21-hydroxylase deficiency"
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                        "volumen" => "51"
                        "paginaInicial" => "298"
                        "paginaFinal" => "304"
                        "link" => array:1 [
                          0 => array:2 [
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              "etiqueta" => "18"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Comprehensive mutation analysis of the CYP21A2 gene&#58; an efficient multistep approach to the molecular diagnosis of congenital adrenal hyperplasia"
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                          "etal" => false
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                        ]
                      ]
                    ]
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                        "link" => array:1 [
                          0 => array:2 [
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              "etiqueta" => "19"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "CYP21A2 mutation update&#58; comprehensive analysis of databases and published genetic variants"
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                            3 => "B&#46; Benavides-Mori"
                            4 => "M&#46; Delea"
                            5 => "J&#46;E&#46; Kolomenski"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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                        "paginaFinal" => "22"
                        "link" => array:1 [
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                            "web" => "Medline"
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                ]
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              "etiqueta" => "20"
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                    0 => array:2 [
                      "titulo" => "Genes&#44; pseudogenes and like genes&#58; the case of 21-hydroxylase in Italian population"
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                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
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                            "web" => "Medline"
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                      ]
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                ]
              ]
            ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Congenital adrenal hyperplasia cases identified by newborn screening in one- and two-screen states"
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                            4 => "W&#46;H&#46; Hannon"
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                      ]
                    ]
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                    0 => array:2 [
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                  ]
                ]
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              "etiqueta" => "22"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Neonatal mass screening for 21-hydroxylase deficiency"
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                          "etal" => false
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1297/cpe.25.1"
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                        "tituloSerie" => "Clin Pediatr Endocrinol"
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                        "paginaInicial" => "1"
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                        "link" => array:1 [
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                            "web" => "Medline"
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                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
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                    ]
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                    0 => array:2 [
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                        "link" => array:1 [
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                    0 => array:2 [
                      "titulo" => "Phenotypic heterogeneity associated with the splicing mutation in congenital adrenal hyperplasia due to 21-hydroxylase deficiency"
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Editorial
Newborn screening for congenital adrenal hyperplasia: beyond 17-hydroxyprogesterone concentrations
Triagem neonatal para hiperplasia adrenal congênita: além das concentrações de 17-Hidroxiprogesterona
Selma Feldman Witchel
University of Pittsburgh, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pediatrics, Pittsburgh, United States
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              "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">17-OHP levels according to genotype &#40;mutation severity group&#44; heterozygous&#44; and wild type&#41;&#59; &#40;A&#41; 17 OHP levels in sample 1&#59; &#40;B&#41; 17 OHP levels in sample 2&#46; Genotype &#40;1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>group null&#59; 2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>group A&#59; 3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>group B&#59; 4<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>group C&#59; 5<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>heterozygous&#59; 6<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>wild type&#41;&#46; <span class="elsevierStyleSup">a</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 <span class="elsevierStyleItalic">versus</span> all other groups&#46; <span class="elsevierStyleSup">b</span><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 <span class="elsevierStyleItalic">versus</span> group 1 and 2&#46; CAH&#44; congenital adrenal hyperplasia&#59; 17-OHP&#44; 17 hydroxyprogesterone&#59; SW&#44; salt-wasting&#59; SV&#44; simple virilizing&#59; C-CAH&#44; classic congenital adrenal hyperplasia&#59; NC&#44; non-classic&#44; late onset&#59; WT&#44; wild-type&#46;</p>"
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    "titulo" => "Newborn screening for congenital adrenal hyperplasia&#58; beyond 17-hydroxyprogesterone concentrations"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The Congenital Adrenal Hyperplasias &#40;CAHs&#41; comprise a group of autosomal recessive disorders due to defects in adrenal steroidogenesis&#46; The most common is 21-hydroxylase deficiency due to mutations in the 21-hydroxylase &#40;<span class="elsevierStyleItalic">CYP21A2</span>&#41; gene&#46; The clinical spectrum ranges from life-threatening adrenal insufficiency to minimal symptoms depending on the specific <span class="elsevierStyleItalic">CYP21A2</span> mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> The clinical phenotype generally reflects the functional activity of the mildest mutation&#46; The prevalence of the classical forms&#44; salt-losing and simple virilizing&#44; differs among populations ranging from approximately 1 in 6000 in India to 1 in 19&#44;000 in Japan&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> The prevalence of non-classic or mild CAH is higher and was reported to be 1 in 2000 among Caucasians in the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">One goal of pediatrics is prevention of disease as exemplified by vaccine development&#46; Another area for prevention is the development of programs to screen and detect newborn infants for whom early intervention is beneficial&#46; For the pediatric endocrinologist&#44; Newborn Screening &#40;NBS&#41; programs for congenital hypothyroidism provide a model in which early intervention prevents poor outcomes&#46; For CAH&#44; the high risk for morbidity and mortality in the classical forms led to the development of a microfilter paper 17-OHP assay in 1977&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> Subsequently&#44; NBS protocols for CAH based on 17-OHP assays were established in over 40 countries&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Considerations prior to the establishment of a screening program include burden of the disorder&#44; knowledge of disease prevalence&#44; sensitivity and specificity of the screening test&#44; and ethical considerations regarding privacy and informed consent&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a> NBS programs are obligated to develop reliable methods to collect filter paper blood spot specimens from all newborn infants&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> The specimens need to be collected and processed within a specific timeframe&#46; The intra-assay and inter-assay coefficients of variation for the laboratory test need to be low&#46; And&#44; finally&#44; a system to locate and inform the parents and appropriate physician&#40;s&#41; is essential to an effective NBS program&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">For CAH&#44; the goal has been to identify infants with salt-losing and simple virilizing forms to prevent the morbidity and mortality due to acute adrenal insufficiency and to recognize affected females&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> NBS for CAH may also identify individuals with non-classic CAH&#46; These individuals may have minimal symptoms and never need hormone replacement therapy&#46; For the families&#44; knowledge of a genetic diagnosis may generate years of anxiety due to the uncertainty regarding development of symptoms&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Hence&#44; a challenge for CAH screening is to assure maximum sensitivity &#40;proportion of positive tests among all individuals with the condition&#41;&#44; maximum positive predictive value &#40;proportion of true positive tests among all tests&#41;&#44; and maximum specificity &#40;proportion of negative tests among all unaffected individuals&#41;&#46; Why is this such an obstacle for NBS for CAH&#63; To achieve nearly 100&#37; sensitivity&#44; the cut-point for 17-hydroxyprogesterone &#40;17-OHP&#41; recall is set such that approximately 1&#37; of all tests are reported as positive&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> At birth&#44; 17-OHP concentrations are high and decline over the first 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h of life&#46; Early specimen collection can thus lead to a false positive result&#46; False positive results &#40;elevated 17-OHP values&#41; can occur in preterm&#44; heterozygous&#44; and stressed infants&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> Some 17-OHP immunoassays cross-react with other steroids such as 17-hydroxypregnenolone sulfate and 15&#946;-hydroxylated compounds leading to false positive results&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> Most 17-OHP assays are performed with commercial kits that may vary due to seasonal temperature fluctuations and unforeseen manufacturer kit changes&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a> False positive results generate anxiety and costs inherent in follow-up evaluation to exclude the diagnosis of CAH&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> False negative results can occur&#44; generally more commonly in girls than in boys&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> Maternal treatment with glucocorticoids can also lead to false negative results&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">These challenges have led to development of strategies designed to improve the positive predictive value&#46; In the cross-sectional study by Kopacek et al&#46;&#44; their goals were to describe the results of a CAH newborn screening embedded in a public health program in Southern Brazil to assess the clinical features of infants identified through this program&#44; and to ascertain the usefulness of <span class="elsevierStyleItalic">CYP21A2</span> genetic testing in the NBS protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> During the two years of this study&#44; a total of 217&#44;965 samples were obtained from 3rd to 40th postnatal days&#46; A time-resolved immunofluorescence assay was used to measure 17-OHP concentrations in dried blood spots&#46; To minimize the false positive results&#44; Kopacek et al&#46; chose to utilize cut-points for four birth-weight tiers stratified by both Brazilian and international experience&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">14&#44;15</span></a> Repeat samples were obtained generally by 3 weeks of age for infants with elevated 17-OHP values or when mothers had used a corticosteroid late in pregnancy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">To assess the value of a second-tier molecular test&#44; the authors performed 17-OHP determinations and <span class="elsevierStyleItalic">CYP21A2</span> genetic testing on the second sample&#46; They utilized a SNaPshot assay to detect 12 common <span class="elsevierStyleItalic">CYP21A2</span> mutations and Multiplex Ligation-dependent Probe Amplification &#40;MLPA&#41; assay to detect rearrangements&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> Elevated 17-OHP values for birth weight cut points were detected in 147 infants&#46; Of these 147 infants&#44; 15 cases were confirmed to have classical CAH&#46; As would be anticipated&#44; infants found to have classical CAH had the highest 17-OHP concentrations at both timepoints&#46; Of the 15 patients found to have classical CAH&#44; all were identified by NBS prior to clinical diagnosis&#44; thus confirming the benefits of the NBS program&#46; Of the remaining 132 positive 17-OHP screening results&#44; the second-tier genetic testing revealed that 7 infants had non-classical CAH&#44; 14 were heterozygotic carriers&#44; and 96 had false positive results&#46; In this situation&#44; knowledge of the specific diagnosis was able to direct appropriate management&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">K&#246;sel et al&#46; also tested a two-tiered approach using <span class="elsevierStyleItalic">CYP21A2</span> molecular testing for samples with elevated 17-OHP values and concluded that despite the slightly higher cost&#44; this testing paradigm could reduce the need for second samples and prevent parental anxiety&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> However&#44; molecular genetic analysis can be complicated because <span class="elsevierStyleItalic">CYP21A2</span> is located in a complex genetic locus in close physical proximity to a highly homologous nonfunctional pseudogene &#40;<span class="elsevierStyleItalic">CYP21A1P</span>&#41;&#46; Most <span class="elsevierStyleItalic">CYP21A2</span> mutations associated with CAH comprise normal <span class="elsevierStyleItalic">CYP21A1P</span> sequence and represent recombination &#40;gene conversion&#41; events between <span class="elsevierStyleItalic">CYP21A2</span> and <span class="elsevierStyleItalic">CYP21A1P</span>&#46; Three neighboring genes&#44; serine&#47;threonine kinase &#40;RP&#41;&#44; complement C4&#44; and Tenascin &#40;TNX&#41;&#44; map to this locus&#46; These four genes form a unit known as the RCCX module&#44; which can be deleted or duplicated&#46; In addition to this copy number variation&#44; the high sequence homology between the functional <span class="elsevierStyleItalic">CYP21A2</span> gene and its nonfunctional pseudogene <span class="elsevierStyleItalic">CYP21A1P</span> complicates the genetic testing&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a> Discriminating deleterious mutations from Variants of Unknown Significance &#40;VUS&#41; discovered by whole genome and exome sequencing may be problematic&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> In some instances&#44; multiple laboratory methods and parental genotyping are necessary to accurately determine a child&#39;s genotype&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Collection of a second blood sample is being used to improve NBS performance parameters&#46; Currently&#44; approximately 22&#37; of American infants are routinely screened a second time&#59; this has improved detection of infants with simple virilizing and NCAH&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> Other paradigms involve use of cut-points based on gestational age&#44; collecting a second sample for 17-OHP immunoassay&#44; liquid chromatography followed by tandem mass spectrometry &#40;LC-MS&#47;MS&#41;&#44; determination of 21-deoxycortisol concentrations&#44; or hormone ratios such as 17-OHP&#47;11-deoxycortisol ratio&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">8&#44;22&#44;23</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Reflection on the details of this study can provide insight and additional perspectives&#46; Two aspects of this study warrant additional comments&#58; &#40;1&#41; maternal use of glucocorticoids and &#40;2&#41; characterization of the IVS2-13A&#47;C&#62;T variant&#46; Some mothers were taking glucocorticoids &#40;GC&#41; prior to delivery&#46; The indications for GC use and type of GC were not described&#46; Did mothers take GC for prenatal treatment to prevent genital virilization for presumably affected infants&#44; for threatened preterm labor&#44; or for another reason&#63;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The authors reported a novel variant&#44; IVS2-13A&#47;C&#62;T&#44; in two individuals&#46; These patients were labeled as being heterozygous carriers&#46; The <span class="elsevierStyleItalic">CYP21A2</span> mutation&#44; IVS2-13A&#47;C&#62;G&#44; involves the same nucleotide and was the most commonly identified mutation in this cohort&#46; The A&#47;C&#62;G mutation creates a novel upstream splice acceptor site resulting in aberrant splicing of intron 2&#44; retention of 19 intronic nucleotides&#44; and a downstream premature termination codon&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> However&#44; the possibility that the A&#47;C&#62;T variant represents a benign variant or VUS has not been addressed&#46; Functional characterization using in vitro expression studies or in silico analysis utilizing bioinformatics prediction software could be used to characterize the functional significance of this intronic variant&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Early detection&#44; confirmation of diagnosis&#44; and treatment are beneficial for individuals with salt-losing and simple virilizing forms of CAH&#46; Pediatricians&#44; family physicians&#44; pediatric endocrinologists&#44; obstetricians&#44; and neonatologists need to be knowledgeable regarding local NBS programs and understand the current limitations of screening for CAH&#46; The future holds promise as the methodology to achieve improved positive predictive values for NBS for CAH evolves&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The author declare no conflicts of interest&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Witchel SF&#46; Newborn screening for congenital adrenal hyperplasia&#58; beyond 17-hydroxyprogesterone concentrations&#46; J Pediatr &#40;Rio J&#41;&#46; 2019&#59;95&#58;257&#8211;9&#46;</p>"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                            0 => "S&#46;F&#46; Witchel"
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                        "tituloSerie" => "J Pediatr Adolesc Gynecol"
                        "fecha" => "2017"
                        "volumen" => "30"
                        "paginaInicial" => "520"
                        "paginaFinal" => "534"
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                    ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Newborn screening for congenital adrenal hyperplasia in India&#58; what do we need to watch out for&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Kishore Kumar"
                            1 => "H&#46; Das"
                            2 => "P&#46; Kini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s13224-015-0712-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Obstet Gynaecol India"
                        "fecha" => "2016"
                        "volumen" => "66"
                        "paginaInicial" => "415"
                        "paginaFinal" => "419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27821980"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Revisiting the prevalence of nonclassic congenital adrenal hyperplasia in US Ashkenazi Jews and Caucasians"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Hannah-Shmouni"
                            1 => "R&#46; Morissette"
                            2 => "N&#46; Sinaii"
                            3 => "M&#46; Elman"
                            4 => "T&#46;R&#46; Prezant"
                            5 => "W&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2017"
                        "volumen" => "19"
                        "paginaInicial" => "1276"
                        "paginaFinal" => "1279"
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0140"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microfilter paper method for 17 alpha-hydroxyprogesterone radioimmunoassay&#58; its application for rapid screening for congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Pang"
                            1 => "J&#46; Hotchkiss"
                            2 => "A&#46;L&#46; Drash"
                            3 => "L&#46;S&#46; Levine"
                            4 => "M&#46;I&#46; New"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jcem-45-5-1003"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "1977"
                        "volumen" => "45"
                        "paginaInicial" => "1003"
                        "paginaFinal" => "1008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/925125"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0145"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population screening for genetic disorders in the 21st century&#58; evidence&#44; economics&#44; and ethics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46;D&#46; Grosse"
                            1 => "W&#46;H&#46; Rogowski"
                            2 => "L&#46;F&#46; Ross"
                            3 => "M&#46;C&#46; Cornel"
                            4 => "W&#46;J&#46; Dondorp"
                            5 => "M&#46;J&#46; Khoury"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000226594"
                      "Revista" => array:6 [
                        "tituloSerie" => "Public Health Genomics"
                        "fecha" => "2010"
                        "volumen" => "13"
                        "paginaInicial" => "106"
                        "paginaFinal" => "115"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19556749"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Newborn screening&#58; a complex system that requires a culture of safety"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "E&#46;R&#46; McCabe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgme.2014.03.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab"
                        "fecha" => "2014"
                        "volumen" => "113"
                        "paginaInicial" => "6"
                        "paginaFinal" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24726176"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nationwide neonatal screening for congenital adrenal hyperplasia in Sweden&#58; a 26-year longitudinal prospective population-based study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Gidl&#246;f"
                            1 => "A&#46; Wedell"
                            2 => "C&#46; Guthenberg"
                            3 => "U&#46; von D&#246;beln"
                            4 => "A&#46; Nordenstr&#246;m"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamapediatrics.2013.5321"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA Pediatr"
                        "fecha" => "2014"
                        "volumen" => "168"
                        "paginaInicial" => "567"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24733564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal screening for congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;C&#46; White"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrendo.2009.148"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Endocrinol"
                        "fecha" => "2009"
                        "volumen" => "5"
                        "paginaInicial" => "490"
                        "paginaFinal" => "498"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19690561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "17-Hydroxyprogesterone in premature infants as a marker of intrauterine stress"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Ersch"
                            1 => "E&#46; Beinder"
                            2 => "T&#46; Stallmach"
                            3 => "H&#46;U&#46; Bucher"
                            4 => "T&#46; Torresani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/JPM.2008.013"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Perinat Med"
                        "fecha" => "2008"
                        "volumen" => "36"
                        "paginaInicial" => "157"
                        "paginaFinal" => "160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18211251"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The influence of seasonality and manufacturer kit lot changes on 17&#945;-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Pearce"
                            1 => "E&#46; Dauerer"
                            2 => "A&#46;G&#46; DiRienzo"
                            3 => "M&#46; Caggana"
                            4 => "N&#46;P&#46; Tavakoli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Pediatr"
                        "fecha" => "2017"
                        "volumen" => "176"
                        "paginaInicial" => "121"
                        "paginaFinal" => "129"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of false-positive newborn screening results on families&#58; a qualitative study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;L&#46; Schmidt"
                            1 => "K&#46; Castellanos-Brown"
                            2 => "S&#46; Childress"
                            3 => "N&#46; Bonhomme"
                            4 => "J&#46;S&#46; Oktay"
                            5 => "S&#46;F&#46; Terry"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/gim.2011.5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genet Med"
                        "fecha" => "2012"
                        "volumen" => "14"
                        "paginaInicial" => "76"
                        "paginaFinal" => "80"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22237434"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Newborn screening for congenital adrenal hyperplasia in New York State"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Pearce"
                            1 => "L&#46; DeMartino"
                            2 => "R&#46; McMahon"
                            3 => "R&#46; Hamel"
                            4 => "B&#46; Maloney"
                            5 => "D&#46;M&#46; Stansfield"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgmr.2016.02.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab Rep"
                        "fecha" => "2016"
                        "volumen" => "7"
                        "paginaInicial" => "1"
                        "paginaFinal" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27331001"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Kopacek"
                            1 => "M&#46;J&#46; Prado"
                            2 => "C&#46;M&#46; da Silva"
                            3 => "S&#46;M&#46; de Castro"
                            4 => "L&#46;A&#46; Beltr&#227;o"
                            5 => "P&#46;R&#46; Vargas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pediatr &#40;Rio J&#41;"
                        "fecha" => "2019"
                        "volumen" => "95"
                        "paginaInicial" => "282"
                        "paginaFinal" => "290"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;Y&#46; Hayashi"
                            1 => "D&#46;F&#46; Carvalho"
                            2 => "M&#46;C&#46; de Miranda"
                            3 => "C&#46; Faure"
                            4 => "C&#46; Vallejos"
                            5 => "V&#46;N&#46; Brito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Endocrinol &#40;Oxf&#41;"
                        "fecha" => "2017"
                        "volumen" => "86"
                        "paginaInicial" => "480"
                        "paginaFinal" => "487"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Screening for congenital adrenal hyperplasia&#58; adjustment of 17-hydroxyprogesterone cut-off values to both age and birth weight markedly improves the predictive value"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46; Olgem&#246;ller"
                            1 => "A&#46;A&#46; Roscher"
                            2 => "B&#46; Liebl"
                            3 => "R&#46; Fingerhut"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2002-021732"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2003"
                        "volumen" => "88"
                        "paginaInicial" => "5790"
                        "paginaFinal" => "5794"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14671170"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of CYP21A2 genotyping assay for the diagnosis of congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;J&#46; Prado"
                            1 => "S&#46;M&#46; de Castro"
                            2 => "C&#46; Kopacek"
                            3 => "M&#46;P&#46; de Mello"
                            4 => "T&#46; Rispoli"
                            5 => "T&#46; Grandi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40291-017-0296-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Diagn Ther"
                        "fecha" => "2017"
                        "volumen" => "21"
                        "paginaInicial" => "663"
                        "paginaFinal" => "675"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28819757"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapid second-tier molecular genetic analysis for congenital adrenal hyperplasia attributable to steroid 21-hydroxylase deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; K&#246;sel"
                            1 => "S&#46; Burggraf"
                            2 => "R&#46; Fingerhut"
                            3 => "H&#46;G&#46; D&#246;rr"
                            4 => "A&#46;A&#46; Roscher"
                            5 => "B&#46; Olgem&#246;ller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1373/clinchem.2004.042416"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem"
                        "fecha" => "2005"
                        "volumen" => "51"
                        "paginaInicial" => "298"
                        "paginaFinal" => "304"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15608154"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comprehensive mutation analysis of the CYP21A2 gene&#58; an efficient multistep approach to the molecular diagnosis of congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Z&#46; Xu"
                            1 => "W&#46; Chen"
                            2 => "D&#46;P&#46; Merke"
                            3 => "N&#46;B&#46; McDonnell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jmoldx.2013.06.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Mol Diagn"
                        "fecha" => "2013"
                        "volumen" => "15"
                        "paginaInicial" => "745"
                        "paginaFinal" => "753"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24071710"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CYP21A2 mutation update&#58; comprehensive analysis of databases and published genetic variants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Simonetti"
                            1 => "C&#46;D&#46; Bruque"
                            2 => "C&#46;S&#46; Fern&#225;ndez"
                            3 => "B&#46; Benavides-Mori"
                            4 => "M&#46; Delea"
                            5 => "J&#46;E&#46; Kolomenski"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/humu.23351"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Mutat"
                        "fecha" => "2018"
                        "volumen" => "39"
                        "paginaInicial" => "5"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29035424"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genes&#44; pseudogenes and like genes&#58; the case of 21-hydroxylase in Italian population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Concolino"
                            1 => "E&#46; Mello"
                            2 => "A&#46; Minucci"
                            3 => "B&#46; Giardina"
                            4 => "E&#46; Capoluongo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cca.2013.05.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chim Acta"
                        "fecha" => "2013"
                        "volumen" => "424"
                        "paginaInicial" => "85"
                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23721949"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Congenital adrenal hyperplasia cases identified by newborn screening in one- and two-screen states"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;K&#46; Held"
                            1 => "S&#46;K&#46; Shapira"
                            2 => "C&#46;F&#46; Hinton"
                            3 => "E&#46; Jones"
                            4 => "W&#46;H&#46; Hannon"
                            5 => "J&#46; Ojodu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ymgme.2015.08.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Genet Metab"
                        "fecha" => "2015"
                        "volumen" => "116"
                        "paginaInicial" => "133"
                        "paginaFinal" => "138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26296712"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neonatal mass screening for 21-hydroxylase deficiency"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Tajima"
                            1 => "M&#46; Fukushi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1297/cpe.25.1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Pediatr Endocrinol"
                        "fecha" => "2016"
                        "volumen" => "25"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26865749"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Utility of a precursor-to-product ratio in the evaluation of presumptive positives in newborn screening of congenital adrenal hyperplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46;Y&#46; Tieh"
                            1 => "J&#46;K&#46; Yee"
                            2 => "R&#46;A&#46; Hicks"
                            3 => "C&#46;S&#46; Mao"
                            4 => "W&#46;N&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/jp.2016.223"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Perinatol"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "283"
                        "paginaFinal" => "287"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27929529"
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Article information
ISSN: 00217557
Original language: English
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