Comparison of transcutaneous bilirubinometer and Icterometer with capillary bilirubin measurement for estimation of bilirubin in neonatal hyperbilirubinemia in the National Referral Hospital, Thimphu

Comparison of transcutaneous bilirubinometer and Icterometer with capillary bilirubin measurement for estimation of bilirubin in neonatal hyperbilirubinemia in the National Referral Hospital, Thimphu | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of transcutaneous bilirubinometer and Icterometer with capillary bilirubin measurement for estimation of bilirubin in neonatal hyperbilirubinemia in the National Referral Hospital, Thimphu Chimi Lhaky Zam, Kuenzang Chhezom, Kalpana Chhetri, Mimi Lhamu Mynak This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9600529/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background : Neonatal jaundice is a very common condition occurring worldwide and is reported to be more prevalent in Asian neonates. It is one of the main reasons for hospital admissions and neonatal morbidity especially during the first week of life. Gold standard for diagnosis of hyperbilirubinemia is investigation of Total serum bilirubin; however, this procedure is invasive and painful. So, a non-invasive and painless screening method is required to be explored and implemented in low resource setting to reduce morbidity and mortality related to neonatal hyperbilirubinemia. Objectives : To determine the accuracy of transcutaneous bilirubinometer (TCB) and icterometer in comparison with capillary bilirubin measurement in neonates with jaundice at the National Referral Hospital, Thimphu. Methods : A cross sectional study was conducted among 723 neonates with hyperbilirubinemia at National Referral Hospital, Thimphu from December 2021 to November 2022. Transcutaneous bilirubinometer and Icterometer measurements were obtained from the neonates for whom the capillary bilirubin measurement was advised. Diagnostic accuracy was assessed using correlation analysis and receiver operating characteristic (ROC) curves. Results : Out of 723 neonates, 55.7% were males and 44.3% were females. There was strong correlation between transcutaneous bilirubinometer and capillary bilirubin (r = 0.72379) with statistically significant p-value of < 0.001). However, TCB values on average overestimated the capillary bilirubin value by 6.2 mg/dl. TCB cut- off ≥ 21 mg/dl demonstrated the best sensitivity (100%) and specificity (84%) for identifying capillary bilirubin measurement ≥ 17 mg/dl with excellent AUC of 0.9123. Although the comparison of the icterometer measurements and the capillary bilirubin showed a statistically significant relation (p < 0.001), the correlation was moderately strong (r = 0.62). The analysis of ROC curve showed 100% sensitivity and 51% specificity for icterometer score of ≥ 3 for identifying capillary bilirubin measurement ≥ 17 mg/dl with good AUC of 0.8849. The icterometer also performed reasonably well compared to capillary bilirubin (score ≥ 3: sensitivity 85% and specificity 56% for capillary bilirubin measurement of ≥ 13 mg/dl.). Conclusion : TCB demonstrated higher diagnostic accuracy than the icterometer. However, the icterometer may serve as a useful screening tool in resource-limited settings where TCB is unavailable. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION Hyperbilirubinemia is one of the most common problems in neonates. It occurs in almost all the new born. Neonatal hyperbilirubenemia occurs due to shorter life span of RBCS, increase in red cell turnover with immature hepatic metabolism of bilirubin. In neonates there is defective conjugation due to decrease in uridine diphospho glucuronyltransferase (UGT) activity along with increase in enterohepatic circulation caused by high level of intestinal beta-glucuronidase. Jaundice can be either physiological or pathological ( 1 ). Physiological jaundice occurs due to physiological immaturity of neonates to handle increase bilirubin production and doesn’t require treatment. About 60% of term and 80% of preterm babies develop jaundice in 1st week of life and 10% of babies are jaundiced up to 1 month of age ( 2 ). It usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks ( 3 ). Pathological jaundice attributes to new born requiring either photo therapy or exchange transfusion. It can be either unconjugated or conjugated hyperbilirubinemia. Direct hyperbilirubinemia or cholestasis is always pathological and warrants rapid evaluation and management ( 4 ). High bilirubin levels can lead to bilirubin- induced neurologic dysfunction (BIND) or kernicterus in some babies. Annually, severe hyperbilirubinemia (Total serum bilirubin > 20 mg/dl) affects 1.1 million infants and extreme hyperbilirubinemia (Total serum bilirubin > 25 mg/dl) affects 4, 81,000 infants ( 5 ) ( 6 ). Kernicterus, although infrequent, has at least 10% mortality and 70% long-term morbidity ( 7 ). Epidemiological evidence suggest that burden of severe neonatal jaundice is unacceptably high in low and middle income countries due to limited availability of screening, monitoring and treatment option ( 7 ). The incidence of severe neonatal jaundice was found to be highest in low to middle income countries like in Africa, followed by Southeast Asian, Eastern Mediterranean and Western Pacific region. The lowest incidence was found in more developed regions like in American and European countries ( 5 ). Main line of treatment for management of neonatal unconjugated hyperbilirubinemia is photo therapy. The indication to start on photo therapy is based on serum bilirubin level, gestation age and age of baby in hours. Currently, three methods are available for measurement of bilirubin level: “Cutaneous” (Icterometer/ transcutaneous bilirubinometer) “Capillary” (using photometer) “Laboratory” (serum bilirubin measurement using chemical reagents) ( 8 ). At present, the Gold standard for diagnosis of hyperbilirubinemia is determined by total serum bilirubin measurement (TSB). As per American academy pediatrics (AAP) recommendation, transcutaneous bilirubinometer or total serum bilirubin measurement test should be performed on every infant who is jaundiced in the first 24 hours after birth and should be assessed for risk of significant hyperbilirubinemia before the discharge ( 9 ). However, frequent blood sampling for monitoring of bilirubin level in admitted babies is unethical and inappropriate when the bilirubin level is below the treatment threshold ( 10 ). On other hand, compared to venous blood, obtaining a capillary sample is less invasive and painful in the neonate and requires less talent and experience. Non-invasive methods including icterometer and transcutaneous bilirubinometer have been developed for assessment of neonatal jaundice. Due to non-invasive nature of transcutaneous bilirubinometer, it has already replaced total serum bilirubin for routine screening in high income county, where these devices are affordable ( 11 ). However, significant difference exists across the population based on the ethnicity, race and bilirubin kinetics. Icterometer is an indirect visual assessment of transcutaneous bilirubin accumulated in the skin and subcutaneous tissue. It is a non-invasive, inexpensive, simple handheld device made of clear plastic, on which are painted five transverse stripes of precise and graded hue. Although, Previous studies validated the original 5color Gosset icterometer (also referred to as the Ingram Icterometer) compared with Total serum bilirubin ( TSB) and was the cheapest device available for bilirubin measurement, it was never widely adopted in western countries because of easy availability of transcutaneous bilirubinometer and serum bilirubin testing ( 8 )( 12 )( 13 ). However, we see rise in new researches with interest in early generation technology. A recent study involving 740 multi ethnic newborns in Boston and Sylhet used the Bili-Ruler, a modern icterometer developed at Harvard University ( 19 ). Reading obtained from nose had a strong correlation to total serum bilirubin proving that a plastic device can achieve diagnostic precision comparable with the Painful and expensive existing methods. Although the study included infants from both the United States and Bangladesh, only a small number were from certain ethnic groups, such as Asian or African descent, which limits how widely the results can be applied. Similarly, most of the international research lack sufficient representation from specific ethnic groups including Bhutanese population. Therefore, their findings may not be directly applicable locally, highlighting the urgent need for local validation in the Bhutanese population. Given the the affordability and non invasive nature, icterometer may work as a screening tool in resource limited setting. This present study aimed to determine the accuracy of icterometer and transcutaneous bilirubinometer with comparison to capillary bilirubin measurement among the neonates in Bhutanese population with a goal of reducing reliance on painful blood sampling and in improving tender neonatal care. METHODOLOGY Study design This is cross sectional study. Study setting The study was conducted at Community Health Unit, Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Thimphu. Study Period The study was conducted at Community Health Unit, JDWNRH from December 2021 to November 2022. Study population Neonates meeting the following inclusion criteria were recruited for the study from December 2021 to November 2022. The inclusion criteria • Neonates < 28 days brought to community health unit for the post-natal visit and for whom the capillary bilirubin measurement was advised at Community Health Unit. The exclusion criteria Those who previously received photo therapy or exchange transfusion. Capillary bilirubin measurement performed at central laboratory, Jigme Dorji Wangchuck National Referral Hospital. SAMPLING SIZE AND SAMPLING METHOD Sample size The sample size was calculated using the formula: Where, n= desired sample size. Z = 1.96, which corresponds to 95% confidence interval. p = set at 0.2or 20% prevalence of neonatal jaundice in the neighboring countries with d= degree of accuracy set at 0.05 for 95% confidence interval. Se=sensitivity of 0.90 or 90% for both icterometer and TCB. Sp=specificity of 0.73 or 73% for icterometer an 0.80 or 80% for TCB. Sampling method The subjects were selected by convenience sampling method. Recruitment of participant Neonates attending the community health unit for routine postnatal visits were screened for neonatal jaundice using transcutaneous bilirubinometer. If the TCB value exceeded the photo therapy threshold according to the American Academy of Pediatrics guidelines, capillary bilirubin testing was advised by the treating physician. Parents were provided with a study information sheet explaining the objectives, procedures, risks, and benefits of the study. Written informed consent was obtained from parents or guardians before enrolment. Data were collected using a structured proforma consisting of three parts. Part A included baseline demographic information such as date of visit, MCH registration number, age, sex, date of birth, mode of delivery, gestational age, and birth weight, obtained from the MCH handbook. Part B included clinical assessment of neonatal jaundice using the Kramer Scale to estimate the severity of hyperbilirubinemia based on the extent of skin discoloration. Part C included investigation results. An average of three TCB measurements was obtained using the MBJ20 Transcutaneous Bilirubinometer. Measurements were taken over the infant’s sternum, and bilirubin levels were estimated based on optical density differences between blue (450 nm) and green (550 nm) wavelengths. When TcB exceeded the treatment threshold, icterometer assessment was performed after consent. The icterometer was gently pressed on the tip of the infant’s nose, and the color of the blanched skin was matched with the corresponding color strips; intermediate shades were assigned a score of 0.5. Infants were subsequently referred to the biochemistry laboratory for capillary bilirubin measurement. Capillary bilirubin was measured using blood obtained by heel prick into a capillary tube according to hospital standard operating procedures. Samples were sent to the biochemistry unit, where they were centrifuged for 1 minute using a hematocrit centrifuge and analyzed using the Toitu BL-200 Bilirubinometer. Neonates were subsequently referred to a pediatrician, and the decision to initiate phototherapy was made by the attending pediatrician. Since neonates were enrolled only after capillary bilirubin testing had already been advised as part of routine care, no additional blood samples were collected for research purposes. DATA MANAGEMENT AND ANALYSIS Data collected using a self-designed proforma were checked for completeness and entered into an EpiData database. Statistical analysis was performed using Stata version 15.5. Descriptive statistics were used to summarize participant characteristics and to calculate mean and standard deviation (SD) bilirubin levels for each icterometer score. Diagnostic accuracy of the icterometer was assessed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios at different hyperbilirubinemia thresholds. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated. Agreement between transcutaneous bilirubinometer and capillary bilirubin measurements was evaluated using Bland–Altman plots, and correlation was assessed using Pearson’s correlation coefficient. A p-value < 0.05 was considered statistically significant RESULTS A total of 756 data was collected from the neonates from CHU, JDWNRH over a period of 12 months (December 2020 to November 2021). However, mother maternal and child health (MCH) identification numbers for 10 neonates were missing. We excluded 23 data which was collected twice during different MCH visit. The rest of 723 neonates were included in the study (figure 2 ). Due to COVID 19 pandemic, we were unable to reach the desired sample size. Demographic characteristic of the study population In the present study, we recruited a total of 723 neonates from CHU, JDWNRH. Among the study population, 4.7% were late preterm, 94.0% were term and 1.3% were post-dated neonates. About 633 neonates (87.6%) were in first week of life. Out of this neonates, 73.6% (n = 532) of the babies were delivered by normal vaginal delivery and 24.1% (n-174) were born by LSCS. More male babies were jaundiced compared to female. Table 1 Demographic characteristics of neonates with hyperbilirubinemia Characteristics n (%) Gender Male Female 403 320 (55.7) (44.3) Age Median (IQR) 7 ( 3 – 7 ) 3–7 days 633 (87.6) 8–14 days 31 (4.3) 15–21 days 59 (8.1) Mode of Delivery SVD 532 (73.6) LSCS 174 (24.1) Assisted Delivery 17 (2.3) Gestation age in Weeks Mean (SD) 38.99 (1.5) 34–36 6/7 week 34 (4.7) 37–41 6/7 weeks 683 (94.0) ≥ 42 weeks 6 (1.3) Birth Weight in KG Mean (SD) 3.01 (0.45) Diagnostic accuracy of TCB to detect different threshold of hyperbilirubinemia Correlation between TCB and capillary bilirubin From the regression analysis (Figure 4), it was found that there was a positive correlation between TCB level and capillary bilirubin (r =0.72379 with p-Value: <0.001) Bland Altman of agreement between capillary bilirubin and TCB measurements Figure 4 , shows a Bland Altman plot representing the mean difference and limit of agreement between capillary bilirubin and TCB. The mean difference was 6.2 mg/dl (SD-1.7). Since the mean difference of 6.2 mg/dl is greater than zero (positive bias), it shows that the TCB values on average overestimated the capillary bilirubin value by 6. 2 mg/dl. It was noted that 18 out of 723 data point exceeded the limit of agreement; 8 exceeded the upper limit and 11 exceeded the lower limit. Only 1 out of the 11 values under the 95% limit of agreement underestimates the cap bilirubin value which means it would be a false negative result. Validity to detect different hyperbilirubinemia threshold by TCB Since majority of capillary bilirubin measurement was obtained within first one week of life, we selected capillary bilirubin cut off of ≥ 17 mg/dl as the reference standard. Table 2 presents Sensitivity, specificity of TCB at different cut off for identifying capillary bilirubin measurement ≥ 17 mg/dl. In the present study, TCB cut- off of ≥ 21 mg/dl demonstrated the best sensitivity (100%) and specificity (84%) for identifying capillary bilirubin measurement ≥ 17 mg/dl. Below the cut- off of 21 mg/dl, sensitivity remained same, while there was drastic reduction in specificity. Likewise, above the cut- off of 21mg/dl, there was increase in specificity with decrease in sensitivity. Table 2 Performance of TCB to detect hyperbilirubinemia (capillary bilirubin reference ≥ 17mg/dl) TCB (mg/dl) Capillary bilirubin (≥ 17mg/dl) sensitivity specificity ≥ 13 100% 0% ≥ 15 100% 0.4% ≥ 17 100% 11% ≥ 20 100% 73% ≥ 21 100% 84% ≥ 22 91% 93% ≥ 23 81% 96% ≥ 25 55% 100% ROC curve for transcutaneous bilirubinometer In figure 5, Using a common cut- off for photo therapy at three days of life as per the AAP guideline for management of neonatal jaundice (capillary bilirubin level of ≥17 mg/dl), ROC curve was generated to analyze the diagnostic performance of TCB. The analysis of ROC curve showed 100% sensitivity and 84% specificity for TCB. The area under the curve was 0.9123 for TCB, indicating a good predictive probability. The point that is highlighted in figure 6A corresponds with TCB cut-off point of ≥ 21 mg/dl. With choosing this cut-off point there are no false negatives which means no single patient with significant hyperbilirubinemia (>17 mg/dl) will be missed. There will be some false positives though as the specificity is only 84% but we rather accept some false positives compared to false negatives for screening purpose. Diagnostic accuracy of Icterometer to detect different threshold of hyperbilirubinemia Correlation between capillary bilirubin and Icterometer From the regression analysis ( figure 6) it was found that there was a positive correlation between icterometer level and capillary bilirubin (r =0.62 with p-value: <0.001). Mean capillary bilirubin concentration associated with Icterometer score In the table 3, we show mean and SD of Icterometer reading and corresponding capillary bilirubin values. Among the total of 723 neonates, all had icterometer reading 2 with most common score observed was score 3, accounting for 238 neonates (32.37%) neonates with score of 3 followed by score 3.5 with 186 cases (25.59%) , and score 2.5 with 164 cases (22.68%) . Lower proportions were observed at higher Icterometer scores, with score 4 in 56 cases (7.61%) , score 4.5 in 25 cases (3.46%) , and score 5 in only 2 cases (0.28%) . With increase in icterometer score, there is increase in capillary bilirubin level demonstratrating a positive relationship between the icterometer score and capillary bilirubin levels. This observation is consistent with the findings presented in Figure 8 , which also shows a positive correlation between the icterometer score and capillary bilirubin levels. Table 3: Icterometer reading and corresponding capillary bilirubin values ICT Score No. (%) Cap bil (SD) Actual reference serum bilirubin 1 0 - - 1.5 0 - - 2 52 (7.19) 12.11 (1.39) 5.55 2.5 164 (22.68) 12.54 (1.57) 7.57 3 238 (32.37) 13.53 (1.71) 10.03 3.5 186 (25.59) 14.66 (1.79) 12.31 4 56 (7.61) 16.02 (1.78) 15.73 4.5 25 (3.46) 17.66 (1.91) 19.06 5 2 (0.28) 19.25 (0.49) >19.06 ICT Score: Icterometer score; cap bil: capillary bilirubin ; SD: Standard deviation Validity to detect different hyperbilirubinemia threshold by Icterometer In table 4, we show sensitivity, specificity, PPV, NPV, positive and negative likelihood ratio of the Icterometer score and corresponding capillary bilirubin values in the study population. As the Icterometer index increases, the sensitivity decreases while the specificity increases. The specificity, NPV, +LR and -LR for icterometer score ≥2 and ≥2.5 couldn’t be generated as there was no capillary bilirubin values < 7.57 mg/dl. Table 4: Predictive characteristics of icterometer in determining the corresponding capillary bilirubin measurement ICT Score Cap bil (mg/dl) Sens Spec PPV NPV +LR - LR ≥2 ≥5.55 99% - 100 % - - - ≥2.5 ≥7.57 92% - 100 % - - - ≥3 ≥10.03 70% 50% 99 % 3% 1.39 0.61 ≥3.5 ≥12.31 46% 87% 90% 38% 3.45 0.62 ≥4 ≥15.73 42% 96% 70% 88% 9.75 0.61 ≥4.5 ≥19.06 57% 97% 15% 99% 17.79 0.44 In table 5, we show sensitivity and specificity of the Icterometer to detect different threshold of hyperbilirubenemia with capillary bilirubin reference . The bilirubin threshold were choose as per the treatment guidelines for low income countries recommended by Bhutani et al and AAP exchange transfusion threshold. Similar to Table 4, when icterometer score increased from 2.5 to 4, sensitivity decreases while the specificity increases for all the bilirubin threshold. Cut off of ≥3 has sensitivity of 73% and specificity of 67% for determining capillary bilirubin measurement of ≥11mg/dl. When the cut off is adjusted to ≥3.5, sensitivity decreases to 39% while the specificity increases to 91%. Likewise, for different bilirubin threshold, as index increases above cut off of ≥3, sensitivity decreases and the specificity increases. While the index decreases below the cut off of ≥3, sensitivity increases and the specificity Table 5: Icterometer scores to identify hyperbilirubinemia (capillary bilirubin reference) at different cutt off Cap bil ≥11 Cap bil ≥13 Cap bil ≥15 Cap bil ≥17 Cap bil ≥20 Sens Spec Sens Spec Sens Spec Sens Spec Sens Spec 77% 46% 96% 16% 99% 11% 100% 8.7% 100% 8.3% 73% 67% 85% 56% 95% 42% 100% 51% 100% 48% 39% 91% 51% 86% 72% 79% 78% 74% 100% 63% 13% 98% 17% 98% 32% 98% 61% 93% 100% 89% ROC Curve for icterometer In figure 7, Using a common cut- off point for photo therapy at day 3 as per the AAP guideline for management of neonatal jaundice (capillary bilirubin level of ≥17 mg/dl), the ROC curve was generated to analyze the diagnostic performance of icterometer at different icterometer cut-off points. The point that is highlighted in figure 7, corresponds with icterometer cut-off point of 3. It showed the highest area under the curve; 0,8849 compared to the other cut-off points. With choosing this cut-off point there are no false negatives which means no single patient with significant hyperbilirubinemia (>17 mg/dl) will be missed. There will be some false positives though as the specificity is only 51% but we rather accept some false positives compared to false negatives for screening purpose. DISCUSSION In the present study, we recruited a total of 723 neonates aged between 34 weeks to > 42 weeks of gestation from CHU, JDWNRH. About 633 neonates (87.6%) were in first week of life. We wanted to determine the accuracy of Icterometer and transcutaneous bilirubinometer was determined in comparison to the capillary bilirubin measurement. Transcutaneous bilirubinometer In evaluation of MBJ20, this present study showed strong correlation coefficient of 0.72 with p-Value: <0.001. This finding was consistent with study from Zimbabwean where they demonstrated correlation coefficient of 0.77(29). Also, study done at Libya, North Africa showed similar finding (r = 0.704 with Value = 0.001) (38). Study done in India, Saudi, and Iran showed a better correlation of 0.82, 0.80, and 0.82 respectively compared to our present study (31) (30) (32). The discrepancy might be because of ethnic and racial variation. The Bland-Altman plot showed that the majority of the measurement fell within 95% confidence interval, showing a strong agreement between the capillary bilirubin and TCB measurement with mean difference of 6 mg/dl. Mean difference obtained in the present study was more compared to that of Chinelo et al, who demonstrated a mean difference between TSB and TCB of 2 mg/dl, indicating that the TCB overestimated the serum bilirubin level(39). This overestimation may lead to abundant numbers of false positive. However, we can ensure that no babies with significant hyperbilirubinemia would be missed out. In Previous studies, sensitivity and specificity of TCB were generated by using different bilirubin cut off as the reference standard. In the present study, since majority of capillary bilirubin measurement was obtained within first one week of life, we selected capillary bilirubin cut off of ≥ 17 mg/dl as the reference standard. In the present study, TCB demonstrated a sensitivity of 100% and specificity 84% for identifying capillary bilirubin measurement ≥ 17 mg/dl. With choosing this cut-off point there are no false negatives which means no single patient with significant hyperbilirubinemia (> 17 mg/dl) will be missed. There will be some false positives though as the specificity is only 84% but we rather accept some false positives compared to false negatives for screening purpose. This finding was similar to the study done in Turkey (40). However, they used cut off of TCB 9mg/dl which was comparatively lower than the cut off used in the present study (21 mg/dl). Similarly, study done in Bangladesh in 2015 demonstrated a sensitivity of 90% and specificity 71% for TcB value of 11 mg/dl in identifying TSB level of 13 mg/dl (41). In another study done in Malaysia, TCB demonstrated a sensitivity of 84.4% and specificity 77.4% for identifying capillary bilirubin measurement ≥ 12 mg/dl (42) Icterometer There is a moderate correlation coefficient (r = 0.62) noted between icterometer and capillary bilirubin measurement in our study. This is similar to the finding demonstrated in the Turkey study. In previous studies, most used TSB cut off of 13 mg/dl (at icterometer index > 3) as threshold for significant hyperbilirubinemia (35) (36). However, due to ethical consideration, this study used capillary bilirubin measurement instead of TSB for comparison with different icterometer score. In this study, icterometer reading ≥ 3 showed sensitivity of 85% and specificity of 56% for detecting capillary bilirubin ≥ 13mg/dl. This finding was comparable to study done in Wisconsin which showed similar finding (sensitivity of 82% with higher specificity of 74%) (35). In present study, icterometer cut off of ≥ 3 had specificity of 56% which means approximately half of the neonates not requiring intervention would be subjected to invasive procedure. Compared to the study done in Turkey, where a score of ≥ 3 had specificity of 48%, present study had greater specificity (36). However, with sensitivity of 85%, we would be missing out only few neonates who might have required bilirubin testing. Therefore, it could be used for screening purpose especially in the health facilities where TCB and serum bilirubin measurement is not available. In the present study, the ROC curve was generated to analyze the diagnostic performance of icterometer at different icterometer cut-off points using a common cut- off point for photo therapy at day 3 as per the AAP guideline for management of neonatal jaundice (capillary bilirubin level of ≥ 17 mg/dl). It showed the highest area under the curve; 0.8849 compared to the other cut-off points. With choosing this cut-off point there was no false negatives which means no single patient with significant hyperbilirubinemia (> 17 mg/dl) will be missed. There will be some false positives though as the specificity is only 51% but we rather accept some false positives compared to false negatives for screening purpose. In a study conducted at Boston and Sylhet with 740 multi ethnic new born, used cut off of Icterometer score ≥ 3.5 for determining TSB ≥ 11mg/dl. It showed a strong correlation to total serum bilirubin with sensitivity of 84.7% and specificity of 83.2% for TSB ≥ 11mg/dl (34). They strongly recommended the use of Icterometer in peripheral communities for early referral of babies with hyperbilirubinemia to higher center. However, in our study, cut off of Icterometer score ≥ 3.5 for determining capillary bilirubin ≥ 11mg/dl showed sensitivity of only 39% and specificity of 91% for TSB ≥ 13mg/dl. According to Anee et al, as the cut off for TSB increases for Icterometer score ≥ 3.5 ranging from 13 mg/dl to 15 mg/dl, sensitivity increased while the specificity decreased (34). Our study showed similar finding. However, the values were comparatively lower and less significant. The difference in the result may be because we used capillary bilirubin measurement instead of TSB as a reference threshold. Hence, cut off > 3.5 wouldn’t be an ideal choice for the use in Bhutanese population. CONCLUSION TCB showed a stronger correlation and higher diagnostic accuracy than the icterometer when compared with capillary bilirubin measurements. A reading < 2.5 on icterometer rules out neonates needing photo therapy with reasonable certainty. Hence, Icterometer may be used in settings where TCB is not available as a screening tool for neonatal jaundice STRENGTH OF THE STUDY We recruited large number of sample size for comparison of noninvasive screening tool to capillary bilirubin. This study showed that Icterometer can be useful for early screening and referral of the patient for serum bilirubin measurement for early intervention. This study validated the current TCB which was being used for jaundice screening in the neonates. LIMITATION OF THE STUDY Since we recruited babies who were jaundiced, we couldn’t validate Icterometer score less than 2. Ideally, Icterometer and TCB were supposed to be compared to ‘Gold standard’ serum bilirubin. However, due to ethical consideration, it was compared to capillary bilirubin level. So, we are not very sure how closely Icterometer and TCB would correlate to serum bilirubin. This study included mostly the term infants. Therefore, the result of the study may not be applicable to preterm babies. Abbreviations AAP - American Academy of Pediatrics BIND - Bilirubin induced neurological dysfunction CI- Confidence Interval FoPGM- Faculty of Postgraduate Medicine JDWNRH- Jigme Dorji Wangchuck National Referral Hospital KGUMSB- Khesar Gyalpo University of Medical Sciences of Bhutan -LR- Negative Likelihood Ratio +LR- Positive Likelihood Ratio NNJ- neonatal jaundice PPV- Positive Predictive Value ROC- Receiver Operator Characteristic Curve r- Regression Coefficient Sen- Sensitivity Spec- Specificity TSB – Total Serum Bilirubin TCB- Transcutaneous bilirubinometer Declarations ACKNOWLEDGEMENT We would like to like to thank the pediatric department and the administration of Jigme Dorji Wangchuck National Referral Hospital for their support. Special thanks go to Mrs. Choki Dolma, a staff member of the MCH unit Care Unit, for helping me identify study participants and collect data. Without her constant support, I could not have completed the study. Funding Declaration This study received partial financial support from Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, in the form of a resident research grant. Howe ever the funding body had no involvement in study design, data collection, analysis, manuscript preparation, or decision to publish. Clinical Trial number- not applicable Consent to Publish Written informed consent for publication of the clinical data was obtained from the parents or legal guardians of the participating neonates. Human Ethics and Consent to Participate Ethical clearance was then sought from the Interim institutional review board (IRB), Medical Education center for research, innovation and training (MECRIT), Khesar Gyalpo University of medical sciences of Bhutan (KGUMSB). Written informed consent was obtained from the parents of all participating neonates before enrollment in the study. IRB approval number: IRB/Approval/PN21-003/2021/521 Author Contribution 1- conceptualization, methodology, project administration, Resources, validation, visualization, writing original draft, writing- review and editing2-4- Resources, supervision, writing- review and editing References Eichenwald EC, Hansen AR, Stark AR. Cloherty and Stark’s Manual of neonatal care. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2012. 337 – 52. Kliegman RM. Nelson Textbook of Pediatrics. 22nd ed. Elsevier; 2024. pp. 871–76. Woodgate P, Jardine LA. Neonatal jaundice. BMJ Clin Evid. 2011;2011:0319. https://pubmed.ncbi.nlm.nih.gov/21920055/ . Agarwal R, Deorari A, Paul V. AIIMS Protocols in Neonatology. CBS Publishers & Distributors Pvt Ltd; 2019. pp. 217–32. Bhutani VK, Zipursky A, Blencowe H, et al. Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res. 2013;74(S1):86–100. https://doi.org/10.1038/pr.2013.208 . Anderson NB, Calkins KL, Neonatal Indirect Hyperbilirubinemia. NeoReviews. 2020;21(11):e749–60. https://doi.org/10.1542/neo.21-11-e749 . Mir SE, van der Geest BAM, Been JV. Management of neonatal jaundice in low- and lower-middle-income countries. BMJ Paediatrics Open. 2019;3(1). https://doi.org/10.1136/bmjpo-2018-000408 . Mirhadi Mussavi P, Niknafs, Bahareh Bijari. Determining the Correlation and Accuracy of Three Methods of Measuring Neonatal Bilirubin Concentration. Iran J Pediatr. 2013;23(3):333. https://pmc.ncbi.nlm.nih.gov/articles/PMC3684480/ . Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF. Hyperbilirubinemia in the Newborn Infant > = 35 Weeks’ Gestation: An Update With Clarifications. Pediatrics. 2009;124(4):1193–8. https://doi.org/10.1542/peds.2009-0329 . Rizvi MR, Alaskar FM, Albaradie RS, Rizvi NF, Al-Abdulwahab K. A Novel Non-invasive Technique of Measuring Bilirubin Levels Using BiliCapture. Oman Med J. 2019;34(1):26–33. https://doi.org/10.5001/omj.2019.05 . Yang S, Liu F, Chen H. Comparison of transcutaneous and serum bilirubin before, under, and after phototherapy in term and late-preterm infants. Kaohsiung J Med Sci. 2019;35(11):715–24. https://doi.org/10.1002/kjm2.12121 . Gupta PC, Kumari S, Mullick DN, Lal UB. Icterometer: a useful screening tool for neonatal jaundice. Indian Pediatr. 1991;28(5):473–6. https://pubmed.ncbi.nlm.nih.gov/1752673/ . Olusanya BO, Slusher TM, Imosemi DO, Emokpae AA. Maternal detection of neonatal jaundice during birth hospitalization using a novel two-color icterometer. Szyld E, ed. PLOS ONE. 2017;12(8):e0183882. https://doi.org/10.1371/journal.pone.0183882 Chimhini GLT, Chimhuya S, Chikwasha V. Evaluation of transcutaneous bilirubinometer (DRAEGER JM 103) use in Zimbabwean newborn babies. Maternal Health Neonatology Perinatol. 2018;4(1). https://doi.org/10.1186/s40748-017-0070-0 . Alsaedi SA. Transcutaneous bilirubin measurement in healthy Saudi term newborns. Saudi Med J. 2016;37(2):142–6. https://doi.org/10.15537/smj.2016.2.13419 . Kumar D, Kumar D. A Prospective Comparison of Serum and Transcutaneous Bilirubin in Indian Neonates. J Pediatr Intensive Care Published online November. 2020;19. https://doi.org/10.1055/s-0040-1721067 . Mahram M, Oveisi S, Jaberi N. Trans-Cutaneous Bilirubinometery versus Serum Bilirubin in Neonatal Jaundice. Acta Medica Iranica. 2015;53(12):764–9. https://pubmed.ncbi.nlm.nih.gov/26749233/ . Şimşek FM, Narter F, Ergüven M. Comparison of transcutaneous and total serum bilirubin measurement in Turkish newborns. Turk J Pediatr. 2014;56(6):612–7. https://pubmed.ncbi.nlm.nih.gov/26388591/ . Lee AC, Folger LV, Rahman M, et al. A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings. Pediatrics. 2019;143(5):e20182039. https://doi.org/10.1542/peds.2018-2039 . Schumacher RE, Thornbery JM, Gutcher GR. Transcutaneous bilirubinometry: a comparison of old and new methods. Pediatrics. 1985;76(1):10–4. https://pubmed.ncbi.nlm.nih.gov/4011341/ . Bilgen H, Ince Z, Ozek E, Bekiroglu N, Ors R. Transcutaneous measurement of hyperbilirubinaemia: comparison of the Minolta jaundice meter and the Ingram icterometer. Ann Trop Paediatr. 1998;18(4):325–8. https://doi.org/10.1080/02724936.1998.11747968 . Madlon-Kay DJ. Recognition of the Presence and Severity of Newborn Jaundice by Parents, Nurses, Physicians, and Icterometer. Pediatrics. 1997;100(3):e3–3. https://doi.org/10.1542/peds.100.3.e3 . Agrawal G, Garg K, Sadasivan Sitaraman, Sarna A. Comparison of Diagnostic Accuracy of Different Sites for Transcutaneous Bilirubin Measurement in Early Preterm Infants. Indian J pediatrics/Indian J Pediatr. 2018;86(1):32–7. https://doi.org/10.1007/s12098-018-2739-4 . Madubuike C, Ugochukwu E, Ezeanosike O, Chukwuka J, Okpara H. Evaluation of MBJ20® Transcutaneous Bilirubinometer in the Assessement of Severity of Neonatal Jaundice. Int J Neonatal Screen. 2016;2(4):8. https://doi.org/10.3390/ijns2040008 . Kaynak-Türkmen M, Aydoğdu SA, Gökbulut C, Yenisey C, Söz O, Cetinkaya-Cakmak B. Transcutaneous measurement of bilirubin in Turkish newborns: comparison with total serum bilirubin. Turk J Pediatr. 2011;53(1):67–74. https://pubmed.ncbi.nlm.nih.gov/21534342/ . Begum NA, Alam K, Shaha A, et al. Transcutaneous Billirubinometry: A Useful Screening Tool for Neonatal Jaundice in Term and Near Term Babies - A Hospital Based Study. Bangladesh J Child Health. 2015;39(3):116–22. https://doi.org/10.3329/bjch.v39i3.31575 . Mohamed M, Nor Rosidah NR, Ramli N, Abdul Majid N, Yacob NM, Nasir A. Comparison between the Transcutaneous and Total Serum Bilirubin Measurement in Malay Neonates with Neonatal Jaundice. Malaysian J Med Sci. 2022;29(1):43–54. https://doi.org/10.21315/mjms2022.29.1.5 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 17 May, 2026 Reviewers invited by journal 16 May, 2026 Editor invited by journal 11 May, 2026 Editor assigned by journal 08 May, 2026 Submission checks completed at journal 08 May, 2026 First submitted to journal 03 May, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9600529","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":636573351,"identity":"91cfd204-ad30-4452-827f-0618fff404b1","order_by":0,"name":"Chimi Lhaky Zam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYDACCcYGhoSCAwwSDAyMD4B8Hj7itBiAtTAbgLSwEdYCIiBa2MBsglr4Zze3bnhgcEdeckb6s8qvOXYybAzMDx/dwGfJnYNtNxIMnhnOlkhIuy27LRnoMDZj4xw8WgwkEkFaDjPOk0g4dltyGzNQCw+bNDFa7OcBGcWS2+qJ15I4WyKZjfHjtsOEtUjcgGhJntnzjFmacdtxHjZmAn7hBwbUzR8Vh21nHE9/+PHntmp7fvbmh4/xaUEAgQQGZh4Qg5ko5WD7DjAw/iBa9SgYBaNgFIwkAADvcUugYmcPUQAAAABJRU5ErkJggg==","orcid":"","institution":"Central regional referra hospital, gelephu","correspondingAuthor":true,"prefix":"","firstName":"Chimi","middleName":"Lhaky","lastName":"Zam","suffix":""},{"id":636573355,"identity":"80a1e5c2-066f-4ce7-bfc5-7c22498c9fe3","order_by":1,"name":"Kuenzang Chhezom","email":"","orcid":"","institution":"Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan","correspondingAuthor":false,"prefix":"","firstName":"Kuenzang","middleName":"","lastName":"Chhezom","suffix":""},{"id":636573365,"identity":"b97dc7ad-8949-40c3-b854-a88e36dee735","order_by":2,"name":"Kalpana Chhetri","email":"","orcid":"","institution":"Jigme Dorji Wangchuck National Referral Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kalpana","middleName":"","lastName":"Chhetri","suffix":""},{"id":636573369,"identity":"8b4d032f-10e9-478d-aff7-7043c4b6e418","order_by":3,"name":"Mimi Lhamu Mynak","email":"","orcid":"","institution":"Jigme Dorji Wangchuck National Referral Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mimi","middleName":"Lhamu","lastName":"Mynak","suffix":""}],"badges":[],"createdAt":"2026-05-03 14:10:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9600529/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9600529/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108979982,"identity":"62d6b90b-9258-424e-a22d-28efa247339a","added_by":"auto","created_at":"2026-05-11 12:02:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":32429,"visible":true,"origin":"","legend":"\u003cp\u003eConceptual Frame work\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/fb866eb94ec32089a24ece9f.png"},{"id":108979913,"identity":"039d15e3-281d-4078-bfeb-13a0123f9247","added_by":"auto","created_at":"2026-05-11 12:02:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17935,"visible":true,"origin":"","legend":"\u003cp\u003eRecruitment of participants\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/7b62bfdf11d54562bdbe92ca.png"},{"id":108979953,"identity":"a330ef43-d793-4076-ab99-b3f127628cc6","added_by":"auto","created_at":"2026-05-11 12:02:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":219791,"visible":true,"origin":"","legend":"\u003cp\u003eLinear regression plot for capillary bilirubin versus Transcutaneous bilirubin measurement\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/fd45bc3613957045ba6d719a.png"},{"id":108979919,"identity":"1f0ec3a1-d67e-42cc-b289-53e964f8a490","added_by":"auto","created_at":"2026-05-11 12:02:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":209625,"visible":true,"origin":"","legend":"\u003cp\u003eBland-Altman plot showing mean difference and limits of agreement of measurement of capillary bilirubin and TCB\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/e76ec7e734fffbe1b32035a3.png"},{"id":108979861,"identity":"fd037a7e-6dac-46e6-a010-9d451a38237b","added_by":"auto","created_at":"2026-05-11 12:02:02","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":227967,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for TCB to identify Capillary bilirubin measurement ≥17 mg/dl\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/9fd970a0d6a1eb411fcef106.png"},{"id":108979925,"identity":"ac7e4e8d-d3d2-4e5b-b198-6638b75bd88e","added_by":"auto","created_at":"2026-05-11 12:02:21","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":212478,"visible":true,"origin":"","legend":"\u003cp\u003eLinear regression plot for capillary bilirubin versus Icterometer measurement\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/f3ef6957cac922d17c8a6037.png"},{"id":108979948,"identity":"cc459bc7-2049-4751-9bfc-a5558bfa6fd1","added_by":"auto","created_at":"2026-05-11 12:02:35","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":170514,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for Icterometer to identify Capillary bilirubin measurement ≥17 mg/d\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/96a022225dc438440becb98b.png"},{"id":108982164,"identity":"2bfee1c2-df96-4d1d-8af7-ec336a2a32ac","added_by":"auto","created_at":"2026-05-11 12:23:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1406834,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9600529/v1/09f6deaa-d814-4797-87e3-2e63a56b15ba.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of transcutaneous bilirubinometer and Icterometer with capillary bilirubin measurement for estimation of bilirubin in neonatal hyperbilirubinemia in the National Referral Hospital, Thimphu","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eHyperbilirubinemia is one of the most common problems in neonates. It occurs in almost all the new born. Neonatal hyperbilirubenemia occurs due to shorter life span of RBCS, increase in red cell turnover with immature hepatic metabolism of bilirubin. In neonates there is defective conjugation due to decrease in uridine diphospho glucuronyltransferase (UGT) activity along with increase in enterohepatic circulation caused by high level of intestinal beta-glucuronidase. Jaundice can be either physiological or pathological (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePhysiological jaundice occurs due to physiological immaturity of neonates to handle increase bilirubin production and doesn\u0026rsquo;t require treatment. About 60% of term and 80% of preterm babies develop jaundice in 1st week of life and 10% of babies are jaundiced up to 1 month of age (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It usually appears 2 to 4 days after birth, and resolves spontaneously after 1 to 2 weeks (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePathological jaundice attributes to new born requiring either photo therapy or exchange transfusion. It can be either unconjugated or conjugated hyperbilirubinemia. Direct hyperbilirubinemia or cholestasis is always pathological and warrants rapid evaluation and management (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHigh bilirubin levels can lead to bilirubin- induced neurologic dysfunction (BIND) or kernicterus in some babies. Annually, severe hyperbilirubinemia (Total serum bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;20 mg/dl) affects 1.1\u0026nbsp;million infants and extreme hyperbilirubinemia (Total serum bilirubin\u0026thinsp;\u0026gt;\u0026thinsp;25 mg/dl) affects 4, 81,000 infants (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Kernicterus, although infrequent, has at least 10% mortality and 70% long-term morbidity (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEpidemiological evidence suggest that burden of severe neonatal jaundice is unacceptably high in low and middle income countries due to limited availability of screening, monitoring and treatment option (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe incidence of severe neonatal jaundice was found to be highest in low to middle income countries like in Africa, followed by Southeast Asian, Eastern Mediterranean and Western Pacific region. The lowest incidence was found in more developed regions like in American and European countries (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMain line of treatment for management of neonatal unconjugated hyperbilirubinemia is photo therapy. The indication to start on photo therapy is based on serum bilirubin level, gestation age and age of baby in hours. Currently, three methods are available for measurement of bilirubin level: \u0026ldquo;Cutaneous\u0026rdquo; (Icterometer/ transcutaneous bilirubinometer) \u0026ldquo;Capillary\u0026rdquo; (using photometer) \u0026ldquo;Laboratory\u0026rdquo; (serum bilirubin measurement using chemical reagents) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt present, the Gold standard for diagnosis of hyperbilirubinemia is determined by total serum bilirubin measurement (TSB). As per American academy pediatrics (AAP) recommendation, transcutaneous bilirubinometer or total serum bilirubin measurement test should be performed on every infant who is jaundiced in the first 24 hours after birth and should be assessed for risk of significant hyperbilirubinemia before the discharge (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). However, frequent blood sampling for monitoring of bilirubin level in admitted babies is unethical and inappropriate when the bilirubin level is below the treatment threshold (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). On other hand, compared to venous blood, obtaining a capillary sample is less invasive and painful in the neonate and requires less talent and experience.\u003c/p\u003e \u003cp\u003eNon-invasive methods including icterometer and transcutaneous bilirubinometer have been developed for assessment of neonatal jaundice. Due to non-invasive nature of transcutaneous bilirubinometer, it has already replaced total serum bilirubin for routine screening in high income county, where these devices are affordable (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, significant difference exists across the population based on the ethnicity, race and bilirubin kinetics.\u003c/p\u003e \u003cp\u003eIcterometer is an indirect visual assessment of transcutaneous bilirubin accumulated in the skin and subcutaneous tissue. It is a non-invasive, inexpensive, simple handheld device made of clear plastic, on which are painted five transverse stripes of precise and graded hue. Although, Previous studies validated the original 5color Gosset icterometer (also referred to as the Ingram Icterometer) compared with Total serum bilirubin ( TSB) and was the cheapest device available for bilirubin measurement, it was never widely adopted in western countries because of easy availability of transcutaneous bilirubinometer and serum bilirubin testing (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, we see rise in new researches with interest in early generation technology. A recent study involving 740 multi ethnic newborns in Boston and Sylhet used the Bili-Ruler, a modern icterometer developed at Harvard University (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Reading obtained from nose had a strong correlation to total serum bilirubin proving that a plastic device can achieve diagnostic precision comparable with the Painful and expensive existing methods. Although the study included infants from both the United States and Bangladesh, only a small number were from certain ethnic groups, such as Asian or African descent, which limits how widely the results can be applied.\u003c/p\u003e \u003cp\u003eSimilarly, most of the international research lack sufficient representation from specific ethnic groups including Bhutanese population. Therefore, their findings may not be directly applicable locally, highlighting the urgent need for local validation in the Bhutanese population.\u003c/p\u003e \u003cp\u003eGiven the the affordability and non invasive nature, icterometer may work as a screening tool in resource limited setting. This present study aimed to determine the accuracy of icterometer and transcutaneous bilirubinometer with comparison to capillary bilirubin measurement among the neonates in Bhutanese population with a goal of reducing reliance on painful blood sampling and in improving tender neonatal care.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"METHODOLOGY","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy design\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis is cross sectional study.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eStudy setting\u003c/h3\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe study was conducted at Community Health Unit, Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Thimphu.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eStudy Period\u003c/h3\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe study was conducted at Community Health Unit, JDWNRH from December 2021 to November 2022.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eNeonates meeting the following inclusion criteria were recruited for the study from December 2021 to November 2022.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eThe inclusion criteria\u003c/h3\u003e\n\u003cp\u003e\u0026bull; Neonates\u0026thinsp;\u0026lt;\u0026thinsp;28 days brought to community health unit for the post-natal visit and for whom the capillary bilirubin measurement was advised at Community Health Unit.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eThe exclusion criteria\u003c/h2\u003e\n \u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eThose who previously received photo therapy or exchange transfusion.\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eCapillary bilirubin measurement performed at central laboratory, Jigme Dorji Wangchuck National Referral Hospital.\u003c/p\u003e\n \u003c/li\u003e\n \u003c/ul\u003e\n\u003c/div\u003e\n\u003ch3\u003eSAMPLING SIZE AND SAMPLING METHOD\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eSample size\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe sample size was calculated using the formula:\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cimg 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\" width=\"325\" height=\"142\"\u003e\u003c/p\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eWhere, n= desired sample size.\u003c/p\u003e\n \u003cp\u003eZ\u0026thinsp;=\u0026thinsp;1.96, which corresponds to 95% confidence interval.\u003c/p\u003e\n \u003cp\u003ep\u0026thinsp;=\u0026thinsp;set at 0.2or 20% prevalence of neonatal jaundice in the neighboring countries with d= degree of accuracy set at 0.05 for 95% confidence interval.\u003c/p\u003e\n \u003cp\u003eSe=sensitivity of 0.90 or 90% for both icterometer and TCB.\u003c/p\u003e\n \u003cp\u003eSp=specificity of 0.73 or 73% for icterometer an 0.80 or 80% for TCB.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eSampling method\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe subjects were selected by convenience sampling method.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eRecruitment of participant\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eNeonates attending the community health unit for routine postnatal visits were screened for neonatal jaundice using transcutaneous bilirubinometer. If the TCB value exceeded the photo therapy threshold according to the American Academy of Pediatrics guidelines, capillary bilirubin testing was advised by the treating physician. Parents were provided with a study information sheet explaining the objectives, procedures, risks, and benefits of the study. Written informed consent was obtained from parents or guardians before enrolment.\u003c/p\u003e\n \u003cp\u003eData were collected using a structured proforma consisting of three parts. Part A included baseline demographic information such as date of visit, MCH registration number, age, sex, date of birth, mode of delivery, gestational age, and birth weight, obtained from the MCH handbook. Part B included clinical assessment of neonatal jaundice using the Kramer Scale to estimate the severity of hyperbilirubinemia based on the extent of skin discoloration.\u003c/p\u003e\n \u003cp\u003ePart C included investigation results. An average of three TCB measurements was obtained using the MBJ20 Transcutaneous Bilirubinometer. Measurements were taken over the infant\u0026rsquo;s sternum, and bilirubin levels were estimated based on optical density differences between blue (450 nm) and green (550 nm) wavelengths. When TcB exceeded the treatment threshold, icterometer assessment was performed after consent. The icterometer was gently pressed on the tip of the infant\u0026rsquo;s nose, and the color of the blanched skin was matched with the corresponding color strips; intermediate shades were assigned a score of 0.5. Infants were subsequently referred to the biochemistry laboratory for capillary bilirubin measurement.\u003c/p\u003e\n \u003cp\u003eCapillary bilirubin was measured using blood obtained by heel prick into a capillary tube according to hospital standard operating procedures. Samples were sent to the biochemistry unit, where they were centrifuged for 1 minute using a hematocrit centrifuge and analyzed using the Toitu BL-200 Bilirubinometer. Neonates were subsequently referred to a pediatrician, and the decision to initiate phototherapy was made by the attending pediatrician. Since neonates were enrolled only after capillary bilirubin testing had already been advised as part of routine care, no additional blood samples were collected for research purposes.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eDATA MANAGEMENT AND ANALYSIS\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eData collected using a self-designed proforma were checked for completeness and entered into an EpiData database. Statistical analysis was performed using Stata version 15.5.\u003c/p\u003e\n \u003cp\u003eDescriptive statistics were used to summarize participant characteristics and to calculate mean and standard deviation (SD) bilirubin levels for each icterometer score. Diagnostic accuracy of the icterometer was assessed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios at different hyperbilirubinemia thresholds. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated.\u003c/p\u003e\n \u003cp\u003eAgreement between transcutaneous bilirubinometer and capillary bilirubin measurements was evaluated using Bland\u0026ndash;Altman plots, and correlation was assessed using Pearson\u0026rsquo;s correlation coefficient. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA total of 756 data was collected from the neonates from CHU, JDWNRH over a period of 12 months (December 2020 to November 2021). However, mother maternal and child health (MCH) identification numbers for 10 neonates were missing. We excluded 23 data which was collected twice during different MCH visit. The rest of 723 neonates were included in the study (figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Due to COVID 19 pandemic, we were unable to reach the desired sample size.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eDemographic characteristic of the study population\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn the present study, we recruited a total of 723 neonates from CHU, JDWNRH. Among the study population, 4.7% were late preterm, 94.0% were term and 1.3% were post-dated neonates. About 633 neonates (87.6%) were in first week of life. Out of this neonates, 73.6% (n\u0026thinsp;=\u0026thinsp;532) of the babies were delivered by normal vaginal delivery and 24.1% (n-174) were born by LSCS. More male babies were jaundiced compared to female.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of neonates with hyperbilirubinemia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e403\u003c/p\u003e \u003cp\u003e320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(55.7)\u003c/p\u003e \u003cp\u003e(44.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e633\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(87.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u0026ndash;14 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(4.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u0026ndash;21 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(73.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLSCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(24.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAssisted Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(2.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eGestation age in Weeks\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e34\u0026ndash;36 6/7 week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(4.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e37\u0026ndash;41 6/7 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e683\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(94.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;42 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth Weight in KG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(0.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic accuracy of TCB to detect different threshold of hyperbilirubinemia\u003c/h2\u003e\n \u003c/div\u003e\n\u003ch2\u003eCorrelation between TCB and capillary bilirubin \u003c/h2\u003e\n\u003cp\u003eFrom the regression analysis (Figure 4), it was found that there was a positive correlation between TCB level and capillary bilirubin (r =0.72379 with p-Value: \u0026lt;0.001)\u0026nbsp;\u003c/p\u003e\n \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eBland Altman of agreement between capillary bilirubin and TCB measurements\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, shows a Bland Altman plot representing the mean difference and limit of agreement between capillary bilirubin and TCB. The mean difference was 6.2 mg/dl (SD-1.7). Since the mean difference of 6.2 mg/dl is greater than zero (positive bias), it shows that the TCB values on average overestimated the capillary bilirubin value by 6. 2 mg/dl. It was noted that 18 out of 723 data point exceeded the limit of agreement; 8 exceeded the upper limit and 11 exceeded the lower limit. Only 1 out of the 11 values under the 95% limit of agreement underestimates the cap bilirubin value which means it would be a false negative result.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eValidity to detect different hyperbilirubinemia threshold by TCB\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eSince majority of capillary bilirubin measurement was obtained within first one week of life, we selected capillary bilirubin cut off of \u0026ge;\u0026thinsp;17 mg/dl as the reference standard. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents Sensitivity, specificity of TCB at different cut off for identifying capillary bilirubin measurement\u0026thinsp;\u0026ge;\u0026thinsp;17 mg/dl.\u003c/p\u003e \u003cp\u003eIn the present study, TCB cut- off of \u0026ge;\u0026thinsp;21 mg/dl demonstrated the best sensitivity (100%) and specificity (84%) for identifying capillary bilirubin measurement\u0026thinsp;\u0026ge;\u0026thinsp;17 mg/dl. Below the cut- off of 21 mg/dl, sensitivity remained same, while there was drastic reduction in specificity. Likewise, above the cut- off of 21mg/dl, there was increase in specificity with decrease in sensitivity.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePerformance of TCB to detect hyperbilirubinemia (capillary bilirubin reference \u0026ge;\u0026thinsp;17mg/dl)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTCB (mg/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCapillary bilirubin (\u0026ge;\u0026thinsp;17mg/dl)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003esensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003especificity\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/br\u003e\u003cp\u003e\u003cstrong\u003eROC curve for transcutaneous bilirubinometer\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn figure 5, Using a common cut- off for photo therapy at three days of life as per the AAP guideline for management of neonatal jaundice (capillary bilirubin level of \u0026ge;17 mg/dl), ROC curve was generated to analyze the diagnostic performance of TCB.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe analysis of ROC curve showed 100% sensitivity and 84% specificity for TCB. The area under the curve was 0.9123 for TCB, indicating a good predictive probability. The point that is highlighted in figure 6A corresponds with TCB cut-off point of \u0026ge; 21 mg/dl. With choosing this cut-off point there are no false negatives which means no single patient with significant hyperbilirubinemia (\u0026gt;17 mg/dl) will be missed. There will be some false positives though as the specificity is only 84% but we rather accept some false positives compared to false negatives for screening purpose. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic accuracy of Icterometer to detect different threshold of hyperbilirubinemia\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation between capillary bilirubin and Icterometer\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom the regression analysis ( figure 6) it was found that there was a positive correlation between icterometer level and capillary bilirubin (r =0.62 with p-value: \u0026lt;0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMean capillary bilirubin concentration associated with Icterometer score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the table 3, we show mean and SD of Icterometer reading and corresponding capillary bilirubin values. Among the total of 723 neonates, all had icterometer reading \u0026nbsp; \u003cimg width=\"10\" height=\"11\" src=\"data:image/png;base64,R0lGODlhDwARAHcAMSH+GlNvZnR3YXJlOiBNaWNyb3NvZnQgT2ZmaWNlACH5BAEAAAAALAAAAAAPABEAgAAAAAAAAAIihI8JEeoMXYJNohbtoVUv5hnZQ5Hj9WFmZ4bue4HRyNVgAQA7\" v:shapes=\"Picture_x0020_87566\" alt=\"image\"\u003e2 with most common score observed was score 3, accounting for 238 neonates (32.37%) neonates with score of 3 followed by \u003cstrong\u003escore 3.5 with 186 cases (25.59%)\u003c/strong\u003e, and \u003cstrong\u003escore 2.5 with 164 cases (22.68%)\u003c/strong\u003e. Lower proportions were observed at higher Icterometer scores, with \u003cstrong\u003escore 4 in 56 cases (7.61%)\u003c/strong\u003e, \u003cstrong\u003escore 4.5 in 25 cases (3.46%)\u003c/strong\u003e, and \u003cstrong\u003escore 5 in only 2 cases (0.28%)\u003c/strong\u003e. With increase in icterometer score, there is increase in capillary bilirubin level demonstratrating a positive relationship between the icterometer \u0026nbsp;score and capillary bilirubin levels. This observation is consistent with the findings presented in \u003cstrong\u003eFigure 8\u003c/strong\u003e, which also shows a positive correlation between the icterometer \u0026nbsp;score and capillary bilirubin levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3:\u0026nbsp;\u003c/strong\u003eIcterometer reading and corresponding capillary bilirubin values\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"552\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003eICT Score\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\u003cstrong\u003eNo.\u0026nbsp;\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\u003cstrong\u003e(%)\u0026nbsp;\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e\u003cstrong\u003eCap bil \u0026nbsp;(SD)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\u003cstrong\u003eActual reference serum bilirubin\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e1\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e0\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e1.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e0\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e2\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e52\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(7.19)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e12.11 (1.39)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e5.55\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e2.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e164\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(22.68)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e12.54 (1.57)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e7.57\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e3\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e238\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(32.37)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e13.53 (1.71)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e10.03\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e3.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e186\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(25.59)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e14.66 (1.79)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e12.31\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e4\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e56\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(7.61)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e16.02 (1.78)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e15.73\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e4.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e25\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(3.46)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e17.66 (1.91)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e19.06\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e2\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e(0.28)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e19.25 (0.49)\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\u0026gt;19.06\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eICT Score: Icterometer score; cap bil: capillary bilirubin ; SD: Standard deviation\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eValidity to detect different hyperbilirubinemia threshold by Icterometer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn table 4, we show sensitivity, specificity, PPV, NPV, positive and negative likelihood ratio of the Icterometer score and corresponding capillary bilirubin values in the study population.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs the Icterometer index increases, the sensitivity decreases while the specificity increases. The specificity, NPV, +LR and -LR for icterometer score \u0026ge;2 and \u0026ge;2.5 couldn\u0026rsquo;t be generated as there was no capillary bilirubin values \u0026lt; 7.57 mg/dl.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4:\u0026nbsp;\u003c/strong\u003ePredictive characteristics of icterometer in determining the corresponding capillary bilirubin measurement\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eICT Score\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eCap\u0026nbsp;bil (mg/dl)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eSens\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eSpec\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003ePPV\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eNPV\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003e+LR\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003eLR\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026ge;2\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026ge;5.55\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e99%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e100 %\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026ge;2.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026ge;7.57\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e92%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e100 %\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e-\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026ge;3\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026ge;10.03\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e70%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e50%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e99 %\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e3%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e1.39\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e0.61\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026ge;3.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026ge;12.31\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e46%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e87%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e90%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e38%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e3.45\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e0.62\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026ge;4\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026ge;15.73\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e42%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e96%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e70%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e88%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e9.75\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e0.61\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\u0026ge;4.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\u0026ge;19.06\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e57%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 65px;\"\u003e97%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e15%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e99%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e17.79\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e0.44\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eIn table 5, we show sensitivity and specificity of the Icterometer to detect different threshold of hyperbilirubenemia with capillary bilirubin reference\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eThe bilirubin threshold were choose as per the treatment guidelines for low income countries recommended by Bhutani et al and AAP exchange transfusion threshold.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilar to \u0026nbsp;Table 4, when icterometer score increased from 2.5 to 4, sensitivity decreases while the specificity increases for all the bilirubin threshold. Cut off of \u0026ge;3 has sensitivity of 73% and specificity of 67% for determining capillary bilirubin measurement of \u0026ge;11mg/dl. When the cut off is adjusted to \u0026ge;3.5, sensitivity decreases to 39% while the specificity increases to 91%. Likewise, for different bilirubin threshold, as index increases above cut off of \u0026ge;3, sensitivity decreases and the specificity increases. While the index decreases below the cut off of \u0026ge;3, sensitivity increases and the specificity \u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5:\u0026nbsp;\u003c/strong\u003eIcterometer scores to identify hyperbilirubinemia (capillary bilirubin reference) at different cutt off\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003eCap\u0026nbsp;bil \u0026ge;11\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003eCap\u0026nbsp;bil \u0026ge;13\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 96px;\"\u003eCap\u0026nbsp;bil \u0026ge;15\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003eCap\u0026nbsp;bil \u0026ge;17\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 108px;\"\u003eCap\u0026nbsp;bil \u0026ge;20\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003eSens\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003eSpec\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003eSens\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003eSpec\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003eSens\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003eSpec\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003eSens\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003eSpec\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003eSens\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003eSpec\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e77%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e46%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e96%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e16%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e99%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e11%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e100%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e8.7%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e100%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e8.3%\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e73%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e67%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e85%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e56%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e95%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e42%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e100%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e51%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e100%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e48%\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e39%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e91%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e51%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e86%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e72%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e79%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e78%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e74%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e100%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e63%\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e13%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e98%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e17%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e98%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e32%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e98%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e61%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e93%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e100%\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e89%\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC Curve for icterometer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn figure 7, Using a common cut- off point for photo therapy at day 3 as per the AAP guideline for management of neonatal jaundice (capillary bilirubin level of \u0026ge;17 mg/dl), the ROC curve was generated to analyze the diagnostic performance of icterometer at different icterometer cut-off points. The point that is highlighted in figure 7, corresponds with icterometer cut-off point of 3. It showed the highest area under the curve; 0,8849 compared to the other cut-off points. With choosing this cut-off point there are no false negatives which means no single patient with significant hyperbilirubinemia (\u0026gt;17 mg/dl) will be missed. There will be some false positives though as the specificity is only 51% but we rather accept some false positives compared to false negatives for screening purpose.\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn the present study, we recruited a total of 723 neonates aged between 34 weeks to \u0026gt;\u0026thinsp;42 weeks of gestation from CHU, JDWNRH. About 633 neonates (87.6%) were in first week of life. We wanted to determine the accuracy of Icterometer and transcutaneous bilirubinometer was determined in comparison to the capillary bilirubin measurement.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003eTranscutaneous bilirubinometer\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn evaluation of MBJ20, this present study showed strong correlation coefficient of 0.72 with p-Value: \u0026lt;0.001. This finding was consistent with study from Zimbabwean where they demonstrated correlation coefficient of 0.77(29). Also, study done at Libya, North Africa showed similar finding (r\u0026thinsp;=\u0026thinsp;0.704 with Value\u0026thinsp;=\u0026thinsp;0.001) (38). Study done in India, Saudi, and Iran showed a better correlation of 0.82, 0.80, and 0.82 respectively compared to our present study (31) (30) (32). The discrepancy might be because of ethnic and racial variation.\u003c/p\u003e \u003cp\u003eThe Bland-Altman plot showed that the majority of the measurement fell within 95% confidence interval, showing a strong agreement between the capillary bilirubin and TCB measurement with mean difference of 6 mg/dl. Mean difference obtained in the present study was more compared to that of Chinelo et al, who demonstrated a mean difference between TSB and TCB of 2 mg/dl, indicating that the TCB overestimated the serum bilirubin level(39). This overestimation may lead to abundant numbers of false positive. However, we can ensure that no babies with significant hyperbilirubinemia would be missed out.\u003c/p\u003e \u003cp\u003eIn Previous studies, sensitivity and specificity of TCB were generated by using different bilirubin cut off as the reference standard. In the present study, since majority of capillary bilirubin measurement was obtained within first one week of life, we selected capillary bilirubin cut off of \u0026ge;\u0026thinsp;17 mg/dl as the reference standard. In the present study, TCB demonstrated a sensitivity of 100% and specificity 84% for identifying capillary bilirubin measurement\u0026thinsp;\u0026ge;\u0026thinsp;17 mg/dl. With choosing this cut-off point there are no false negatives which means no single patient with significant hyperbilirubinemia (\u0026gt;\u0026thinsp;17 mg/dl) will be missed. There will be some false positives though as the specificity is only 84% but we rather accept some false positives compared to false negatives for screening purpose. This finding was similar to the study done in Turkey (40). However, they used cut off of TCB 9mg/dl which was comparatively lower than the cut off used in the present study (21 mg/dl). Similarly, study done in Bangladesh in 2015 demonstrated a sensitivity of 90% and specificity 71% for TcB value of 11 mg/dl in identifying TSB level of 13 mg/dl (41). In another study done in Malaysia, TCB demonstrated a sensitivity of 84.4% and specificity 77.4% for identifying capillary bilirubin measurement\u0026thinsp;\u0026ge;\u0026thinsp;12 mg/dl (42)\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eIcterometer\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThere is a moderate correlation coefficient (r\u0026thinsp;=\u0026thinsp;0.62) noted between icterometer and capillary bilirubin measurement in our study. This is similar to the finding demonstrated in the Turkey study. In previous studies, most used TSB cut off of 13 mg/dl (at icterometer index\u0026thinsp;\u0026gt;\u0026thinsp;3) as threshold for significant hyperbilirubinemia (35) (36). However, due to ethical consideration, this study used capillary bilirubin measurement instead of TSB for comparison with different icterometer score.\u003c/p\u003e\u003cp\u003eIn this study, icterometer reading\u0026thinsp;\u0026ge;\u0026thinsp;3 showed sensitivity of 85% and specificity of 56% for detecting capillary bilirubin \u0026ge;\u0026thinsp;13mg/dl. This finding was comparable to study done in Wisconsin which showed similar finding (sensitivity of 82% with higher specificity of 74%) (35).\u003c/p\u003e\u003cp\u003eIn present study, icterometer cut off of \u0026ge;\u0026thinsp;3 had specificity of 56% which means approximately half of the neonates not requiring intervention would be subjected to invasive procedure. Compared to the study done in Turkey, where a score of \u0026ge;\u0026thinsp;3 had specificity of 48%, present study had greater specificity (36).\u003c/p\u003e\u003cp\u003eHowever, with sensitivity of 85%, we would be missing out only few neonates who might have required bilirubin testing. Therefore, it could be used for screening purpose especially in the health facilities where TCB and serum bilirubin measurement is not available. In the present study, the ROC curve was generated to analyze the diagnostic performance of icterometer at different icterometer cut-off points using a common cut- off point for photo therapy at day 3 as per the AAP guideline for management of neonatal jaundice (capillary bilirubin level of \u0026ge;\u0026thinsp;17 mg/dl). It showed the highest area under the curve; 0.8849 compared to the other cut-off points. With choosing this cut-off point there was no false negatives which means no single patient with significant hyperbilirubinemia (\u0026gt;\u0026thinsp;17 mg/dl) will be missed. There will be some false positives though as the specificity is only 51% but we rather accept some false positives compared to false negatives for screening purpose.\u003c/p\u003e\u003cp\u003eIn a study conducted at Boston and Sylhet with 740 multi ethnic new born, used cut off of Icterometer score\u0026thinsp;\u0026ge;\u0026thinsp;3.5 for determining TSB\u0026thinsp;\u0026ge;\u0026thinsp;11mg/dl. It showed a strong correlation to total serum bilirubin with sensitivity of 84.7% and specificity of 83.2% for TSB\u0026thinsp;\u0026ge;\u0026thinsp;11mg/dl (34). They strongly recommended the use of Icterometer in peripheral communities for early referral of babies with hyperbilirubinemia to higher center. However, in our study, cut off of Icterometer score\u0026thinsp;\u0026ge;\u0026thinsp;3.5 for determining capillary bilirubin\u0026thinsp;\u0026ge;\u0026thinsp;11mg/dl showed sensitivity of only 39% and specificity of 91% for TSB\u0026thinsp;\u0026ge;\u0026thinsp;13mg/dl.\u003c/p\u003e\u003cp\u003eAccording to Anee et al, as the cut off for TSB increases for Icterometer score\u0026thinsp;\u0026ge;\u0026thinsp;3.5 ranging from 13 mg/dl to 15 mg/dl, sensitivity increased while the specificity decreased (34). Our study showed similar finding. However, the values were comparatively lower and less significant. The difference in the result may be because we used capillary bilirubin measurement instead of TSB as a reference threshold.\u003c/p\u003e\u003cp\u003eHence, cut off \u0026gt;\u0026thinsp;3.5 wouldn\u0026rsquo;t be an ideal choice for the use in Bhutanese population.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eTCB showed a stronger correlation and higher diagnostic accuracy than the icterometer when compared with capillary bilirubin measurements. A reading\u0026thinsp;\u0026lt;\u0026thinsp;2.5 on icterometer rules out neonates needing photo therapy with reasonable certainty. Hence, Icterometer may be used in settings where TCB is not available as a screening tool for neonatal jaundice\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSTRENGTH OF THE STUDY\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eWe recruited large number of sample size for comparison of noninvasive screening tool to capillary bilirubin.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThis study showed that Icterometer can be useful for early screening and referral of the patient for serum bilirubin measurement for early intervention.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThis study validated the current TCB which was being used for jaundice screening in the neonates.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eLIMITATION OF THE STUDY\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSince we recruited babies who were jaundiced, we couldn\u0026rsquo;t validate Icterometer score less than 2.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eIdeally, Icterometer and TCB were supposed to be compared to \u0026lsquo;Gold standard\u0026rsquo; serum bilirubin. However, due to ethical consideration, it was compared to capillary bilirubin level. So, we are not very sure how closely Icterometer and TCB would correlate to serum bilirubin.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThis study included mostly the term infants. Therefore, the result of the study may not be applicable to preterm babies.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAAP - American Academy of Pediatrics \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBIND - Bilirubin induced neurological dysfunction \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI- Confidence Interval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFoPGM- Faculty of Postgraduate Medicine \u003c/p\u003e\n\u003cp\u003eJDWNRH- Jigme Dorji Wangchuck National Referral Hospital \u003c/p\u003e\n\u003cp\u003eKGUMSB- Khesar Gyalpo University of Medical Sciences of Bhutan \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e-LR- Negative Likelihood Ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e+LR- Positive Likelihood Ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNNJ- neonatal jaundice\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPV- Positive Predictive Value\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eROC- Receiver Operator Characteristic Curve r- Regression Coefficient\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSen- Sensitivity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpec- Specificity \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTSB \u0026ndash; Total Serum Bilirubin \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTCB- Transcutaneous bilirubinometer\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to like to thank the pediatric department and the administration of Jigme Dorji Wangchuck National Referral Hospital for their support. Special thanks go to Mrs. Choki Dolma, a staff member of the MCH unit Care Unit, for helping me identify study participants and collect data. Without her constant support, I could not have completed the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received partial financial support from Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, in the form of a resident research grant. Howe ever the funding body had no involvement in study design, data collection, analysis, manuscript preparation, or decision to publish.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial number-\u0026nbsp;\u003c/strong\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of the clinical data was obtained from the parents or legal guardians of the participating neonates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e Ethical clearance was then sought from the Interim institutional review board (IRB), Medical Education center for research, innovation and training (MECRIT), Khesar Gyalpo University of medical sciences of Bhutan (KGUMSB). Written informed consent was obtained from the parents of all participating neonates before enrollment in the study.\u003c/p\u003e\n\u003cp\u003eIRB approval number: IRB/Approval/PN21-003/2021/521\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e1- conceptualization, methodology, project administration, Resources, validation, visualization, writing original draft, writing- review and editing2-4- Resources, supervision, writing- review and editing\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEichenwald EC, Hansen AR, Stark AR. Cloherty and Stark\u0026rsquo;s Manual of neonatal care. 8th ed. Philadelphia: Lippincott Williams \u0026amp; Wilkins; 2012. 337\u0026thinsp;\u0026ndash;\u0026thinsp;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKliegman RM. Nelson Textbook of Pediatrics. 22nd ed. 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Turk J Pediatr. 2011;53(1):67\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/21534342/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/21534342/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBegum NA, Alam K, Shaha A, et al. Transcutaneous Billirubinometry: A Useful Screening Tool for Neonatal Jaundice in Term and Near Term Babies - A Hospital Based Study. Bangladesh J Child Health. 2015;39(3):116\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3329/bjch.v39i3.31575\u003c/span\u003e\u003cspan address=\"10.3329/bjch.v39i3.31575\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohamed M, Nor Rosidah NR, Ramli N, Abdul Majid N, Yacob NM, Nasir A. Comparison between the Transcutaneous and Total Serum Bilirubin Measurement in Malay Neonates with Neonatal Jaundice. Malaysian J Med Sci. 2022;29(1):43\u0026ndash;54. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21315/mjms2022.29.1.5\u003c/span\u003e\u003cspan address=\"10.21315/mjms2022.29.1.5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9600529/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9600529/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Neonatal jaundice is a very common condition occurring worldwide and is reported to be more prevalent in Asian neonates. It is one of the main reasons for hospital admissions and neonatal morbidity especially during the first week of life. Gold standard for diagnosis of hyperbilirubinemia is investigation of Total serum bilirubin; however, this procedure is invasive and painful. So, a non-invasive and painless screening method is required to be explored and implemented in low resource setting to reduce morbidity and mortality related to neonatal hyperbilirubinemia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e: To determine the accuracy of transcutaneous bilirubinometer (TCB) and icterometer in comparison with capillary bilirubin measurement in neonates with jaundice at the National Referral Hospital, Thimphu.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A cross sectional study was conducted among 723 neonates with hyperbilirubinemia at National Referral Hospital, Thimphu from December 2021 to November 2022. Transcutaneous bilirubinometer and Icterometer measurements were obtained from the neonates for whom the capillary bilirubin measurement was advised. Diagnostic accuracy was assessed using correlation analysis and receiver operating characteristic (ROC) curves.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Out of 723 neonates, 55.7% were males and 44.3% were females. There was strong correlation between transcutaneous bilirubinometer and capillary bilirubin (r = 0.72379) with statistically significant p-value of \u0026lt; 0.001). However, TCB values on average overestimated the capillary bilirubin value by 6.2 mg/dl. TCB cut- off ≥ 21 mg/dl demonstrated the best sensitivity (100%) and specificity (84%) for identifying capillary bilirubin measurement ≥ 17 mg/dl with excellent AUC of 0.9123.\u003c/p\u003e\n\u003cp\u003eAlthough the comparison of the icterometer measurements and the capillary bilirubin showed a statistically significant relation (p \u0026lt; 0.001), the correlation was moderately strong (r = 0.62). The analysis of ROC curve showed 100% sensitivity and 51% specificity for icterometer score of ≥ 3 for identifying capillary bilirubin measurement ≥ 17 mg/dl with good AUC of 0.8849. The icterometer also performed reasonably well compared to capillary bilirubin (score ≥ 3: sensitivity 85% and specificity 56% for capillary bilirubin measurement of ≥ 13 mg/dl.).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: TCB demonstrated higher diagnostic accuracy than the icterometer. However, the icterometer may serve as a useful screening tool in resource-limited settings where TCB is unavailable.\u003c/p\u003e","manuscriptTitle":"Comparison of transcutaneous bilirubinometer and Icterometer with capillary bilirubin measurement for estimation of bilirubin in neonatal hyperbilirubinemia in the National Referral Hospital, Thimphu","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 10:59:26","doi":"10.21203/rs.3.rs-9600529/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"224081861317375645507461888844082362227","date":"2026-05-17T10:08:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-16T04:20:42+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-11T06:33:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-08T04:36:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-08T04:36:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-05-03T13:59:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f745d9c1-9152-4c02-916c-e985bf8b9b28","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"224081861317375645507461888844082362227","date":"2026-05-17T10:08:01+00:00","index":33,"fulltext":""},{"type":"reviewersInvited","content":"18","date":"2026-05-16T04:20:42+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-05-11T06:33:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-05-08T04:36:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-05-08T04:36:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-05-03T13:59:19+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-16T04:23:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 10:59:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9600529","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9600529","identity":"rs-9600529","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}