Diagnostic Utility of Cord Blood Thyroid Stimulating Hormone in Congenital Hypothyroidism in the Era of Expanded Newborn Screening

Abstract

Even in the era of expanded newborn screening, utility of cord blood thyroid stimulating hormone (cTSH) for diagnosis of congenital hypothyroidism (CH) cannot be marginalised. This study was to assess the diagnostic utility of cTSH [ 20 lIU/L for screening CH. Generation of new cTSH value was the main outcome measure, to increase specificity. Designed as a cross-sectional analytic study in the neonatal unit of teaching hospital, 1200 term neonates with birth weight C2500 g, with no perinatal complications were included. Newborn cTSH assay was done by chemiluminescence. All screen positive were followed up on day five, 14 and 28 of life, to rule in or out CH (true or false positive). Positive predictive value and specificity were calculated. Receiver operating characteristic (ROC) was done to assess diagnostic accuracy of cTSH [ 20 lIU/L and to ascertain new cutoff to reduce false positivity. Of 1200 newborns screened, 69 (5.8%) were screen positive and followed up. In five, CH was confirmed (true positive); one in 240 newborns required thyroxine therapy. False positivity was noted in 59. Recall and dropouts were 6.25 and 7.2% respectively. Median cTSH of screen, true and false positives were 28.8, 43.5 and 27.2 lIU/L respectively. Comparison of median values of cord blood (U = 59; p = 0.017) and day five serum TSH (U = 0.0; p \ 0.001) among true and false positive subjects were statistically significant. Specificity calculated was 94.6% and positive predictive value 7.25%. ROC generated new permissible cTSH cutoff value of 30 lIU/L. In conclusion, an extended cTSH cutoff value of 30 lIU/L improves specificity.

Unfolding the perinatal factors that affect cord blood thyroid stimulating hormone levels- an experience from a rural centre in southern India

“…In the Indian setting, the CB-TSH value of more than 20 micro IU/ml is considered as a safe cutoff for recall [2,3,5,[17][18][19][20]31] . In our study, 4.82% of neonates had CB-TSH values more than 20 micro IU/ml, similar to Laxmi Narayana (5.42) [22] which reflects a higher recall rate when compared to Manglik (1.83%) [3] and Wu (2.27%) [37] but even higher values were observed in other studies by Nasheda (5.8%) [39] , Poornima Kumar (8.1%) [29] and Gupta (11.5%) [6] , etc. Several authors have postulated that CB-TSH levels can be influenced by factors such as perinatal asphyxia, difficult deliveries_ Rashmi [9] and Laxmi Narayana [22] , perinatal stress events, birth weight, gestational age,_ Tim et al [27] , male sex_ Chan Ly [25] and Mahin Hashemipour [28] and following instrumental delivery, or by cesarean section as the mode of delivery_ Chan Ly [25] , but the mechanism is poorly understood.…”

“…In the USA, the incidence of CH has shown an increase (from approximately 1:4,100 to 1:2,350) over the past few decades, this could be from including the babies with transient hypothyroidism (TH). Though the exact cause for increased incidence globally is not known but factors that are implicated include changes in screening methods (lower TSH cutoff), obtaining the screening specimen earlier (closer to the TSH surge after birth), geographic and ethnic variations [39] , and iodine deficiency, or excess [4,9] . The Indian council of medical research (ICMR) introduced a screening program for congenital hypothyroidism among neonates in 2007.…”

Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics

“…For example, CSF is most commonly used for screening monoamine neurotransmitter deficiencies [112]. Cord blood has been used in the detection of thyroid stimulating hormone (TSH) in the screening of congenital hypothyroidism [113]. Human skin fibroblasts were used for in vitro detection of the defect in isoleucine catabolism in ethylmalonic encephalopathy by Sahebekhtiari et al [114].…”

Congenital hypothyroidism in India: A systematic review and meta-analysis of prevalence, screen positivity rates, and etiology

“…Seventy-nine studies were included in the systematic review, and 70 studies in the meta-analysis. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 The flow...…”