Optimizing Cord Blood Thyroid Stimulating Hormone Cutoff for Screening of Congenital Hypothyroidism—Experience from Screening 164,000 Newborns in a Tertiary Hospital in India

Abstract

Background and Objectives: In our institution, we have an ongoing newborn thyroid screening (NBS) program since July 2001. In the initial 9 months, we used cord blood thyroid-stimulating hormone (TSH) (CBTSH) cutoff of 20 mIU/L and thereafter the cutoff was increased to 25 mIU/L. Our objective was to evaluate whether a CBTSH cutoff of 25 mIU/L is sensitive and cost-effective in NBS of congenital hypothyroidism (CH). Materials and Methods: All in-born babies are screened and those with CBTSH ≥25 mIU/L are recalled for confirmatory TSH/T4/FT4 tests. CH is confirmed with elevated TSH and low T4/FT4. Those with CBTSH 20–24.99 mIU/L were recalled for confirmatory tests in initial period of our NBS and prospectively between January and August 2017. Statistical analysis was done to derive positive predictive value and sensitivity to diagnose CH for each CBTSH between 20 and 30 mIU/L. Results: A total of 164,163 neonates were screened from July 2001 to August 2017. Of the 2352 babies with CBTSH ≥25–30 mIU/L, 1763 returned for retesting and 5 confirmed as CH (4 gland-in-situ and 1 absent uptake on nuclear scan). Of the 14,742 screened during the study period, 195 of the 293 babies with CBTSH 20–24.99 mIU/L returned for retesting and none diagnosed as CH. A CBTSH of 25 mIU/L has 99.2% sensitivity and 97.5% specificity. A lower screen TSH cutoff 20 mIU/L would result in recall of additional 300 babies/year with no definite improvement in sensitivity. Conclusions: Our data justify the continuation of using screen TSH cutoff of 25 mIU/L while using cord blood for NBS in our population. With a diverse and large population, it is important that we use feasible regional screen cutoffs for optimal use of our resources.

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...…”

“…The prevalence of CH was estimated separately for neonates in endemic and non-endemic regions, neonates born to mothers with thyroid disease and preterm neonates. Meta-analysis of 54 studies that included term neonates from non-endemic regions (55 datasets, and 819 559 neonates) 11 , 12 , 13 , 14 , 17 , 19 , 20 , 21 , 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 55 , 56 , 57 , 62 , 63 , 64 , 65 , 67 , 68 , 69 , 71 , 72 , 73 , 74 , 75 , 76 , 80 gave a pooled prevalence of 0·97 per 1 000 neonates (95% confidence interval/CI: 0·9 to 1·04), which is about 1 in 1 031 neonates. The I 2 statistic was 92%, while the variance in pooled estimates was narrow.…”

Prevalence of Congenital Hypothyroidism in India: Mapping and Critical Appraisal

“…Hence, we used data only from studies with a sample size ≥9500 in whom the criteria to diagnose CH were clear and appropriate. [ 3 4 5 6 7 8 9 10 11 12 13 14 15 16 ]…”

“…A study from Vellore, another city in Tamil Nadu, reported a prevalence (1:1334) comparable to the rest of the country. [ 5 8 9 ] The latter study used cord blood TSH with a relatively higher cut-off (25 μIU/ml) to define screen positivity but reported no increase in the sensitivity to detect CH with the use of lower cut-offs (20 μIU/ml) in a subset. [ 9 ] Another large study from Delhi reported only a marginal increase (from 1:1706 to 1:1657) in the prevalence of CH when the TSH cut-off for screen positivity was lowered from 20 to 10 μIU/ml.…”

“…[ 5 8 9 ] The latter study used cord blood TSH with a relatively higher cut-off (25 μIU/ml) to define screen positivity but reported no increase in the sensitivity to detect CH with the use of lower cut-offs (20 μIU/ml) in a subset. [ 9 ] Another large study from Delhi reported only a marginal increase (from 1:1706 to 1:1657) in the prevalence of CH when the TSH cut-off for screen positivity was lowered from 20 to 10 μIU/ml. [ 10 ] These observations indicate no/minimal effect of varied TSH cut-offs to define screen positivity on the prevalence rates of CH.…”