Newborn Screening in the US May Miss Mild Persistent Hypothyroidism

Kilberg, Marissa J; Rasooly, Irit R.; LaFranchi, Stephen; Bauer, Andrew J.; Hawkes, Colin P.

doi:10.1016/j.jpeds.2017.09.003

Cited by 53 publications

(38 citation statements)

References 24 publications

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“…1 Similar increases have been observed in Western Australia (from 0.17 cases per 1000 births between 1981 and 1987 to 0.35 cases per 1000 births between 1988 and 1998) 2 and Italy (from 0.33 cases per 1000 births between 1987 and 1998 to 0.51 cases per 1000 births between 1999 and 2008). 10 Potential explanations for this observation include changes in population ethnic composition, 3 environmental changes (such as perchlorate exposure), 11 iodine deficiency, 12 and changes in clinical practice 13 and awareness that lead to better detection. Many screening programs' cutoff levels have changed over time, which may partially explain the increased case ascertainment rate.…”

Section: Congenital Hypothyroidism (Cht)mentioning

confidence: 99%

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland

McGrath

Hawkes

McDonnell³

et al. 2018

Pediatrics

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BACKGROUND AND OBJECTIVES: Congenital hypothyroidism (CHT) is one of the most common preventable causes of learning disability. Newborn screening with whole-blood thyroidstimulating hormone measurements was introduced in the Republic of Ireland in 1979 and is coordinated from a single center with an unchanged protocol since its inception. Our objective in this study was to describe the incidence of CHT in the Republic of Ireland over the past 37 years in the context of a complete national population and an unchanged screening protocol. METHODS:The newborn screening records of all individuals who were diagnosed with CHT between 1979 and 2016 were reviewed. Infants with positive screening results had a whole-blood thyroid-stimulating hormone value of ≥15 mU/L at 72 to 120 hours of life; values of 8 to 15 mU/L required a repeat whole-blood screening test.

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Section: Congenital Hypothyroidism (Cht)mentioning

confidence: 99%

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland

McGrath

Hawkes

McDonnell³

et al. 2018

Pediatrics

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“…There is currently no agreement on the optimal whole-blood TSH concentration to be used as a cut-off for CHT screening; significant variation is seen in cut-offs used between NBS programmes [12], but our data show that using a threshold of 8 mU/L instead of 10 mU/L will identify infants with decompensated and permanent CHT. International consensus guidelines [3] recommend starting treatment immediately if venous thyroxine concentrations are below the reference range for age, and this was seen in 13 (40%) of the infants with initial whole-blood TSH concentrations between 8 and 9.9 mU/L.…”

Section: Discussionmentioning

confidence: 86%

“…In 2006, a study of Irish pregnant women suggested a prevalence of iodine deficiency of 55% in women tested in summer and of 23% in women tested in winter [14]. Higher TSH concentrations are seen soon after delivery [15], and the timing of screening influences the distribution of whole-blood TSH concentrations [12]. Thus, a cut-off of 8–9.9 mU/L is likely to identify more falsely elevated TSH concentrations if applied to a NBS programme that performs initial screening before day 3.…”

Section: Discussionmentioning

confidence: 99%

Permanent Decompensated Congenital Hypothyroidism in Newborns with Whole-Blood Thyroid-Stimulating Hormone Concentrations between 8 and 10 mU/L: The Case for Lowering the Threshold

et al. 2018

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Background: Congenital hypothyroidism (CHT) has a reported incidence of approximately 1 in 2,000–4,000 births. There is no consensus on the optimal cut-off whole-blood thyroid-stimulating hormone (TSH) concentration that should be used for newborn screening (NBS). The NBS programme in the Republic of Ireland has used a cut-off of 8 mU/L since 1979. The aim of this study was to determine if raising the cut-off to 10 mU/L would have resulted in undetected cases of permanent or decompensated CHT. Methods: All cases of CHT with a screening whole-blood TSH concentration between 8.0 and 9.9 mU/L were identified from the Republic of Ireland’s NBS programme. Baseline demographics and imaging results were recorded. All cases over 3 years of age were evaluated to determine if CHT was permanent or transient. Results: Of 2,361,174 infants screened in the Republic of Ireland between July 1979 and December 2016, a total of 1,063 babies were diagnosed with CHT and treated with levothyroxine. This included 33 (3.5%) infants with a whole-blood TSH concentration between 8 and 9.9 mU/L. Thirteen of these 33 infants had decompensated hypothyroidism with low plasma free thyroxine level at diagnosis and 9 (41%) of the 21 evaluable cases have confirmed permanent CHT. Conclusion: Although lowering screening TSH cut-offs can increase the cost of NBS, as well as anxiety for families, many infants with borderline increases in whole-blood TSH concentrations on NBS have persistent CHT and low thyroxine concentrations in infancy. We recommend that this is considered when developing and reviewing NBS protocols for identifying infants with CHT.

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“…TSH concentrations continue to fall beyond the first days of life and are typically within the normal childhood range by one month of age. A recent US report highlighted the risk of missing children with mild persistent CH, given that the majority of programmes did not use age‐adjusted cut‐offs for repeat samples . Conversely, many programmes do apply lower cut‐offs for late samples, including the New Zealand programme that utilizes a lower threshold of TSH ≥8 mIU/L amongst repeat samples or those collected >14 days .…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, even a modestly lower threshold would reduce screen performance across the population as a whole (due to lower specificity and PPV highlighted the risk of missing children with mild persistent CH, given that the majority of programmes did not use age-adjusted cut-offs for repeat samples. 26 Conversely, many programmes do apply lower cutoffs for late samples, including the New Zealand programme that utilizes a lower threshold of TSH ≥8 mIU/L amongst repeat samples or those collected >14 days. 5 We excluded samples collected >7 days from our cohort as these would be anticipated to include a high proportion of repeat samples in babies with initially abnormal results, many of whom would subsequently be confirmed to have CH, and would therefore not be representative of TSH levels amongst the general population.…”

Section: Con Clus Ionsmentioning

confidence: 99%

The impact of demographic factors on newborn TSH levels and congenital hypothyroidism screening

Heather

Derraik

Webster

et al. 2019

Clinical Endocrinology

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Context Optimal newborn screening thyroid‐stimulating hormone (TSH) cut‐offs are contentious. Analysis of demographic factors that impact screen TSH levels may help explain international variance and provide guidance to screening programmes. Objective To determine the influence of demographic factors on newborn screening TSH levels and screening performance parameters. Design and Setting National, retrospective population study using blood spot TSH cards from the New Zealand newborn screening programme in 2010‐2015. Patients 325 685 blood spot cards. Main Outcome Measures Likelihood of exceeding specific TSH thresholds (TSH ≥5, ≥10 and ≥15 mIU/L) and group‐specific screening performance parameters. Results The likelihood of high TSH levels differed between ethnic groups. Pacific Island infants were more than twice as likely to have high‐normal TSH levels (≥5 and ≥10 mIU/L) and nearly twice as likely to have a positive screen (≥15 mIU/L) as New Zealand Europeans. Māori or Chinese ethnicity, male sex, younger gestational age and greater socio‐economic deprivation scores were also associated with high‐normal TSH levels. At a TSH threshold ≥15 mIU/L, screening sensitivity was lowest (88.89% vs 95.83% overall) and PPV greatest (88.89% vs 62.84%) amongst Asian infants. Early samples were more than three times as likely to reach the screen‐positive threshold and more likely to yield a false‐positive result (PPV 20.00% vs 68.87%, P = 0.004). Conclusions Newborn TSH levels are impacted by a number of demographic variables, particularly ethnicity and age at sample collection. Screening performance may be improved through the use of targeted thresholds.

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Newborn Screening in the US May Miss Mild Persistent Hypothyroidism

Cited by 53 publications

References 24 publications

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland

Permanent Decompensated Congenital Hypothyroidism in Newborns with Whole-Blood Thyroid-Stimulating Hormone Concentrations between 8 and 10 mU/L: The Case for Lowering the Threshold

The impact of demographic factors on newborn TSH levels and congenital hypothyroidism screening

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