Transcutaneous bilirubin reliability during and after phototherapy depending on skin color

doi:10.21203/rs.3.rs-3552302/v1

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Research Article

Transcutaneous bilirubin reliability during and after phototherapy depending on skin color

https://doi.org/10.21203/rs.3.rs-3552302/v1

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Journal Publication

published 06 Apr, 2024

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Purpose

Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of neonates according to Neomar’s neonatal skin color scale.

Methods

Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color.

Results

We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74–0.83) and after (0.79–0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 hours after discontinuing phototherapy (0.78).

Conclusions

Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar’s scale during and mainly after phototherapy may help reduce the number of blood samples required.

Neonatal jaundice

Serum bilirubin

Hyperbilirubinemia

Transcutaneous bilirubin

Skin color

Phototherapy

Controversies exist on the reliability of jaundice meters during and after phototherapy in covered skin. Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale.

What is New:

We verified correlation between serum and transcutaneous bilirubin in covered skin in a multiethnic population depending on skin color based on our own validated neonatal skin color scale during and after phototherapy.

Neonatal jaundice affects 60–85% of term infants, with pathological jaundice being the most common cause of readmission to the neonatal unit [1–2]. It is potentially dangerous due to acute and chronic bilirubin encephalopathy [3]. The gold standard to measure serum bilirubin (SB) levels is by means of a blood sample and, for patients under phototherapy, it means frequent blood draws which causes pain and increases the risk of anemia and infections [4]. For these reasons, non-invasive methods like the determination of transcutaneous bilirubin (TcB) have been proposed for patients undergoing phototherapy or after discontinuing it. Several authors have found a good correlation (0.78–0.96) between TcB and SB before phototherapy, but controversies remain as to the reliability of jaundice meters during and after phototherapy [5–16]. Their reliability seems to be influenced as well by skin color, gestational age, TcB device, measurement site and TSB level [5, 7, 9, 11, 13–17]. Newborns in our reference area belong to different ethnic populations and have different skin tones. Although the TcB/SB correlation seems to be good regardless of skin color, TcB tends to overestimate SB to a higher degree in dark-skinned neonates [5, 6, 13, 18]. Jaundice meters may be less reliable in neonates receiving phototherapy or after interrupting it, although studies have found conflicting results [12, 15, 19–26]. Most studies found the correlation to be better when TcB was measured in covered skin, however most of them were not multiethnic [20, 23, 25, 27–32]. The instruction manual for the Jaundice Meter JM-105^™ states that it is not appropriate for use on neonates who recieve phototherapy [33].

We decided to conduct this study to test the correlation between SB and TcB, both in covered (cTcB) and in exposed skin (eTcB), during and after phototherapy in a multicultural population including preterm babies, with the aim of reducing physical discomfort to the newborn, as well as economic costs. A previous study we conducted showed that the TcB/SB correlation before phototherapy depended on skin color as determined by Neomar’s neonatal skin color scale but not on gestational age [34]. Our hypotheses were that cTcB correlated well with SB during phototherapy and immediately afterwards, however eTcB did not until 24 hours after discontinuation of phototherapy, with a significantly different bias depending on skin color.

This was a prospective observational study conducted at the neonatal unit of a tertiary care center with approximately 1400 deliveries per year which compared the levels of bilirubin using two techniques: TcB and SB. All the neonates admitted to our hospital with an indication for phototherapy during the study period (October 2016 to March 2019) were offered to participate. The indication of phototherapy was based on SB according to our hospital guidelines [35–36]. Patients were enrolled if their parents agreed to and signed a written informed consent (see Appendix 1). Exclusion criteria were the presence of extensive skin lesions in the sternal zone (i.e., melanocytic nevus). None of the participants had been under phototherapy when first recruited. We did not exclude patients who had ABO/Rh incompatibility. We included preterm neonates because they are more prone to requiring phototherapy and thus need more bilirubin measurements.

Neonates in our hospital are routinely assigned to a color group at 24 hours of life according to Neomar’s skin color scale (4 categories: light -color1-, medium-clear -color2-, medium-dark -color3- and dark -color4-) (see Appendix 2) [34]. We also routinely measure TcB in the mid-sternal area as recommended by the manufacturer (Dräger Jaundice Meter JM-105™, Minolta, Dräger Medical GmbH, Lübeck, Germany) for the screening of neonatal jaundice. Our laboratory determines SB with a diazo method (COBAS INTEGRA® 400 plus analyzer, Roche Diagnostics).

Prior to the initiation of phototherapy, we covered an area of the mid sternum with a 26-mm-photo-opaque patch (NeoSmile™ temperature probe cover, NEOTECH PRODUCTS, USA) (Fig. 1) that we kept on during phototherapy and after its discontinuation until a normal rebound SB measuring was obtained.

Phototherapy was provided continuously by standard overhead phototherapy units (Dräger Photo Therapy 4000 with 4 lamps, Dräger Medical GmbH, Lübeck, Germany) placed 35–40 cm above the neonate, which delivered irradiation in a central area (EBi) of 1.6 ± 0.3 microWatts/cm2. The lamps (Draeger Fluorescent light “blue” 2M 21 010) deliver blue light with a spectral wavelength of 400–550 and a peak of 450 nm. During phototherapy, the infants’ eyes were routinely covered by opaque eye pads that were regularly checked by nursing personnel at 3hour intervals during feeds. Phototherapy was only discontinued during TcB measurement or SB sampling. The cTcB measurement was performed on the center of the covered mid-sternal area under the photo-opaque patch, and the eTcB measurement on the adjacent exposed area. Paired cTcB/SB and eTcB/SB dyads were taken within 20 minutes of each other.

We collected data on gestational age, gender, prematurity, mother’s country of origin and ethnicity (surrogate for the participant’s ethnicity), birth weight, feeding choice, paired eTcB/SB and cTcB/SB (see Data collection sheet, Appendix 3).

Statistical analyses: We described quantitative variables (gestational age, birth weight, cTcB, eTcB and SB), which were normally distributed, using the mean and standard deviation (SD), and categorical variables (gender, prematurity, breastfeeding, mother’s origin/ethnicity) with frequencies and percentages. We compared the four-color groups in terms of gestational age, prematurity rate, birth weight, sex and rate of breastfeeding. Qualitative variables were compared with the Pearson’s chi-squared or Fisher’s exact test as appropriate and quantitative variables with ANOVA. During and after phototherapy, paired cTcB/SB and eTcB/SB measurements were compared, both globally and according to skin color. We assessed the association between TcB and SB with Pearson’s correlation coefficient. Bland Altman plots were used to evaluate the concordance between techniques (cTcB/eTcB and SB). Mean difference (bias) and its limits of agreement (LOA) were reported for the whole sample and for each color group. We also performed a multiple linear regression to check the relation between SB-cTcB bias and cTcB measurements as well as gestational age and skin color group. The choice of these potential confounders was based on clinical criteria. These analyses were performed separately at each observation stage (during phototherapy, after phototherapy and 23 hours after phototherapy). Results from these analyses were expressed as β coefficient, its 95%CI and p-value. Significance was set at the p < 0.05 level. To perform statistical analyses we used STATA version 15.1 (StataCorp, College Station, TX, USA).

Our hospital Ethics Committee accepted and approved this study (ref. 2015/6519/I), which was conducted following the principles of the Helsinki Declaration.

We recruited 200 neonates who required phototherapy during the study period (color1: 44 patients, color2: 111 patients, color3: 41 patients, color4: 4 patients). Table 1 describes characteristics of our population and color groups. There were no differences among the color groups in terms of gender and rate of breastfeeding at discharge. However, there were statistically significant differences in terms of gestational age, prematurity, birth weight and mother’s origin. Jaundice was idiopathic in 93 neonates (46.5%), prematurity-related in 81 (40.5%) and due to ABO-isoimmunization in 26 (13%).

Table 1

Characteristics of our study population.
	Global (n = 200)	Color 1 (n = 44)	Color 2 (n = 111)	Color 3 (n = 41)	Color 4 (n = 4)	p
Gestational age (weeks) (mean, SD)	37.25 (2.3) [30-41.7]	35.79 (2.6) [30-41.4]	37.36 (2.1) [33.1–41.7]	38.38 (1.8) [33.6–41.1]	38.64 (2.8) [34.6–40.6]	< 0.001^a
Gender, female, n (%)	92 (46)	25 (56.8)	48 (43.2)	18 (43.9)	1 (25)	0.362^b
Birth weight (g) (mean, SD)	2757.04 (625.54)	2477.07 (703.34)	2782.39 (554.85)	2941.22 (621.39)	3245.50 (688.47)	0.005^a
Prematurity, n (%)	81 (40.5)	29 (65.9)	44 (39.6)	7 (17.1)	1 (25)	< 0.001^b
Breastfed, n (%)	195 (97.5)	41 (93.2)	109 (98.2)	41 (100)	4 (100)	0.192^b
Mother’s origin, n (%) -Subsaharian -Latin American -Caribbean -East Asian -European -Magrebin -Southeast Asian	1 (0.5) 26 (13.0) 5 (2.5) 12 (6.0) 67 (33.5) 19 (9.5) 70 (35.0)	0 (0.0) 4 (9.1) 0 (0.0) 1 (2.3) 32 (72.7) 5 (11.4) 2 (4.5)	0 (0.0) 18 (16.2) 2 (1.8) 8 (7.2) 34 (30.6) 13 (11.7) 36 (32.4)	0 (0.0) 3 (7.3) 2 (4.9) 3 (7.3) 1 (2.4) 1 (2.4) 31 (75.6)	1 (25.0) 1 (25.0) 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0)	< 0.001^b
TcB: transcutaneous bilirubin; SB: serum bilirubin; SD: standard deviation
^aANOVA, ^bChi-squared test

We analyzed 296 paired SB/cTcB and 291 paired SB/eTcB measurements. Just before initiating phototherapy, the mean SB was 15.3 mg/dL (range 7.6–27.8 mg/dL), and the mean TcB was 15.86 mg/dL (range 8.8–20 mg/dL).

The mean age at initiation of the first phototherapy session was 68.04 (SD 37.18) hours and the mean duration of phototherapy per session was 21.6 (SD 7.9) hours. A single session of phototherapy was sufficient for 172 children, whereas 28 required two sessions, and only 2 required three.

The Pearson correlation coefficient between eTcB and SB was weak during phototherapy (r 0.54, 95%CI 0.46;0.62) (see Fig. 2), with the SB-eTcB bias Bland Altman estimation of 4.31 mg/dL (95%LOA − 2.46;11.07). However, the correlation improved globally following discontinuation of phototherapy to 0.78 (95%CI 0.72;0.83), still being weak the first 24 hours (r 0.60–6.62) but significantly improving afterwards (r 0.81–0.90) (see Figs. 3 and 4). The Bland Altman bias estimation and its LOA between eTcB and SB globally measured after phototherapy resulted in 0.18 mg/dL (95%LOA − 3.42;3.78).

The global Pearson correlation coefficient between cTcB and SB was strong during phototherapy (r 0.79, 95%CI 0.74;0.83) (see Fig. 5), with the SB-cTcB bias Bland Altman estimation of -1.02 mg/dL (95%LOA − 4.19;2.16). Figure 6 shows the Pearson’s correlation coefficients between cTcB and SB during phototherapy depending on skin color. Bland Altman bias estimation and its LOA between cTcB and SB depending on skin color during phototherapy resulted in: -0.70 mg/dL (95%LOA − 4.77;3.36) for color1, -1.17 mg/dL (95%LOA − 4.90;2.56) for color2, -1.97 mg/dL (95% LOA − 5.99;2.06) for color3, -3.42 mg/dL (95%LOA − 5.61;-1.22) for color4.

The Pearson correlation coefficient between cTcB and SB was also strong globally after discontinuing phototherapy [0.84 (95%CI 0.79;0.88)] (Fig. 7). This correlation coefficient remained good when analyzing it depending on the hours after discontinuing treatment and on the neonate’s skin color (see Figs. 8 and 9). Bland Altman bias estimation and its LOA between cTcB and SB depending on skin color after phototherapy resulted in: -0.43 mg/dL (95%LOA − 3.78;2.92) for color 1, -0.91 mg/dL (95%LOA − 3.74;1.92) for color 2, -1.66 mg/dL (95%LOA − 4.87;1.55) for color 3, -3.46 mg/dL (95%LOA − 6.78;-0.13) for color4.

Table 2 shows results from the multiple linear regression. The bias SB-cTcB during phototherapy was significantly associated with cTcB measurement as well as with the newborn’s gestational age. On the other hand, the bias SB-cTcB after phototherapy was significantly associated with cTcB measurement and the newborn’s skin color as determined by Neomar’s scale (only significant for color3). Finally, after 23 hours of phototherapy, the bias SB-cTcB was significantly associated only with skin color (again, significantly associated with color3).

Table 2

β coefficients and its confidence intervals (CI) of the associations between SB-cTcB bias and cTcB, gestational age and skin color. Results during phototherapy, after phototherapy and phototherapy > 23h.
	β	95% CI		p-value	n
cTcB during phototherapy	-0.45	-0.52	-0.39	0.000	286
Gestational age	0.20	0.10	0.29	0.000
Color1
1	0.00
2	-0.01	-0.49	0.47	0.970
3	-0.40	-1.02	0.23	0.212
cTcB after phototherapy	-0.09	-0.18	-0.01	0.037	180
Gestational age	-0.01	-0.13	0.11	0.864
Color1
1	0.00
2	-0.35	-0.96	0.25	0.252
3	-0.95	-1.75	-0.15	0.020
cTcB after phototherapy > 23h	-0.08	-0.20	0.03	0.148	128
Gestational age	0.02	-0.13	0.16	0.818
Color1
1	0.00
2	-0.35	-1.09	0.38	0.342
3	-1.24	-2.34	-0.14	0.027
CI: Confidence interval.

Jaundice meters are reliable and can be used at the newborn's bedside by minimally-trained personnel with numerous reported benefits [6, 10–11, 16, 24, 37, 38]. They measure bilirubin in subcutaneous tissue and are designed to agree as closely as possible with SB [6, 16]. Some authors have hypothesized that because bilirubin deposits in the subcutaneous fat in a similar way as in the brain, TcB could more closely estimate brain bilirubin [30]. Most clinical studies have shown an accuracy of ± 3mg/dL between TcB and SB [6, 13, 36]. Despite being a powerful tool to clinically screen for neonatal hyperbilirubinemia, some controversies remain as to their reliability depending on exposure to phototherapy. Phototherapy eliminates bilirubin from the skin and subcutaneous tissue by producing photoisomers (i.e., lumirubin and photobilirubin) that are more easily eliminated (through urine and stools). Bilirubin concentration in the skin decreases more rapidly than in blood and phototherapy blanches exposed skin whereas covered skin remains jaundiced, at least initially [15, 19, 22, 27, 39, 40]. Therefore, jaundice meters may be less reliable in neonates receiving phototherapy or less than 24 hours after interrupting it [22]. TcB measurements are not widely accepted as a surrogate measure of SB during phototherapy, although not all the authors agree in this statement [12, 15, 20, 23–26, 28, 39–42]. But there seems to be a better TcB/SB correlation when TcB is measured in covered skin [15, 19, 24–27, 29–32, 40, 43–46].

In our present study, we did obtained a much stronger TcB/SB correlation when measured in covered skin (r 0.79) versus exposed skin (r 0.54) (see Figs. 2 and 5). The cTcB/SB correlation was strong during phototherapy globally (r 0.79, see Fig. 5) and for color groups 2 and 4 (r 0.80–0.90), being worse for color1 and color3 (r 0.67–0.70, see Fig. 6). However, correlation is lower than we reported in our previous study before initiating phototherapy (r 0.91–0.94) [13]. The mean SB-cTcB bias ± 2SD obtained was − 1.02 ± 3.24 mg/dL (95% CI -4.19;2.16) globally, with a wider range than reported in our previous study before initiating phototherapy, but with acceptable limits (± 3.24 mg/dL) [13]. These results are in agreement with Tan, who found that phototherapy reduced the correlation between cTcB (JM-103^™) and SB but did not completely eliminate it [19]. Katayama found moderate cTcB/SB correlations before and during phototherapy in a retrospective study using JM-103^™ in term Japanese neonates [42]. Rylance used JM-103^™ and also described that cTcB was reliable to guide phototherapy in Black Malawian neonates under phototherapy [47]. In line with Rylance, Johnson used JM-103^™ in Haitian newborns to assess cTcB reliability during phototherapy and concluded that it could be safely used to guide jaundice treatment [45]. Castro used the JM-103^™ to study cTcB/SB and eTcB/SB correlations during phototherapy in a small number of mostly Caucasian term and moderate-late preterm neonates and found the cTcB/SB correlation to be relatively strong (r 0.74) but concluded that the range of agreement limits was too wide (-3.8 to 4.6 mg/dL) to use cTcB to guide phototherapy. Only Costa-Posada and Pendse used the same device as us (JM-105^™). Costa-Posada found a good cTcB/SB correlation during phototherapy in Caucasian preterm and term newborns with SB-cTcB biases that rarely exceeded 2 mg/dL [32]. Pendse found a good cTcB/SB correlation in preterm Indian neonates, stating that cTcB is a good option in low-income countries with high prematurity rates and with SB measurements often unavailable [44]. Most of these studies (except Ozkan’s who used an older version of the Minolta device -JM-101^TM- [28]) agree with our results. But, unlike our study, these were not performed in multiethnic populations nor specified skin color. In addition to this, most of them only included term infants, except for Pendse and Huzelbos which only included preterm infants [40, 44]. Many other studies done with BiliChek drew contradictory conclusions [15, 21, 25, 29, 31, 39, 46]. However, most of these studies, except Murli and Reyes´s, found cTcB useful during phototherapy. The contradictory results could be explained by different study populations, inclusion or not of preterm infants, irradiance of phototherapy, etc [46].

The weaker correlation and wider ranges of SB-cTcB biases obtained during phototherapy could be explained by the higher levels of SB in these patients, as in most cases levels of TcB above 15 mg/dL need to be confirmed with a blood sample due to a worsening correlation with risk of underestimation [8, 13, 24, 36, 48]. However, once a spontaneous decline in TcB is detected and maintained, the risk of subsequent hyperbilirubinemia is low [36]. The delayed decrease of cTcB relative to SB during the first hours of treatment could also contribute to the worse cTcB-SB correlation during phototherapy. Also the older age of infants undergoing phototherapy could contribute to a worse correlation, as skin pigmentation may increase with age [44, 46].

Some data show that the TcB/SB correlation worsens with decreasing gestational age, at the same time that the threshold for phototherapy decreases [49]. Despite the controversies, there seems to be a strong correlation in preterm babies, that may vary depending on gestational age [10, 12–13, 15, 24, 26, 40, 44, 50–52]. In line with this last statement we found that the SB-cTcB bias during phototherapy depended on gestational age, increasing by + 0.2 with every increasing gestational week, thus decreasing overestimation. These results agree with most authors except Zecca and Costa-Posada’s [15, 30–32, 45, 47]. We did not observe this dependence on gestational age after phototherapy.

Several authors have also studied the usefulness of TcB to control rebound bilirubin after phototherapy. Limited data exist about when eTcB is reliable after phototherapy, being historically recommended after 18–24 hours [19]. In a prospective observational study using JM-103^™, Grabenhenrich estimated that eTcB underestimated SB by 2.4 mg/dL (SD 2.1 mg/dL) during the first 8 hours post-phototherapy, giving a safety margin of 7 mg/dL below the treatment threshold to skip measuring SB and where less than 1% of the neonates actually requiring phototherapy would be given a falsely negative result. This study, performed in single ethnic, included mostly Caucasian newborns and none required a second course of phototherapy [14]. More recently and using BiliChek, Akin observed that the best moment to measure cTcB was at least seven hours after stopping phototherapy (r 0.98) [53]. Juster-Reicher obtained similar results (eight hours) in a population of basically Caucasian Israeli neonates (r 0.65–0.80) [54]. Castro found that 12 hours after stopping phototherapy, cTcB correlated well (r 0.90) with SB and that 94.9% of the decisions based on cTcB would have been correct, stating that cTcB is useful to screen the need for a second course of phototherapy [23]. In agreement with Castro, our results show a good correlation between cTcB and SB globally after phototherapy (r 0.84), improving 12 hours after discontinuing treatment from 0.75 to 0.91 (see Figs. 7 and 8). Our sample was much larger and multiethnic.

We reported correlations among different color groups, all of them similar (r 0.84–0.88, see Fig. 9). Modern jaundice meters use specific algorithms to isolate bilirubin from other skin chromophores [6]. However, in accordance to our previous study and to other authors, the mean SB-cTcB bias varied depending on the group, being the overestimation higher and the range wider in darker colors (see Table 2) [4–5, 11, 13, 34, 37, 55–56].

The most currently-used jaundice meters, BiliChek^™ and JM-103/105^™, have a similar performance. However, the first one needs a disposable tip for each use, increasing costs, is more time-consuming and may also underestimate SB at higher levels (> 15mg/dL) [6, 7, 9, 36]. Clinically speaking, it is safer to slightly overestimate SB than underestimate in order to avoid misclassification of newborns requiring phototherapy.

To the best of our knowledge, ours is the first reported prospective study analyzing both cTcB and eTcB reliability during and after phototherapy in multiethnic populations of term and preterm newborns according to skin color. Classifying newborns by ethnic group is complex, imprecise and unreliable, due to the variability of skin tones within an ethnic group. We used a reliable validated neonatal skin color classification [13, 34].

Our study has limitations. First, we could not recruit many patients belonging to color4 given the characteristics of our population, and the small sample size could render our results not comparable for this group. Second, we only used one device (JM-105^TM), for which our results may not be generalizable to other jaundice meters. Lastly, we collected data at a single center, therefore our results may not be generalizable.

The cTcB/SB correlation was strong for term and preterm infants after phototherapy treatment and, to a lesser extent, during treatment. The SB-cTcB bias estimation fell within acceptable limits during phototerapy (± 3.24 mg/dL). However, eTcB only correlated well with SB after 24 hours of finalizing phototherapy.

Our study supports the reliability of cTcB to assess SB during and after phototherapy in multiethnic populations of preterm and term babies, with statistical differences among skin color after treatment and on gestational age during treatment. This may help reduce the number of blood samples, thus reducing both newborn pain and economic costs during jaundice treatments. A larger sample for color4 may increase reliability of cTcB in this group.

SB: serum bilirubin; TcB: transcutaneous bilirubin; cTcB: transcutaneous bilirubin in covered skin; eTcB: transcutaneous bilirubin in uncovered or exposed skin; SD: standard deviation; LOA: limits of agreement.

Funding and competing interests: The authors declare that they have not received any funds or grants for this research, nor have any competing interests to disclose.

Acknowledgments:

We would like to thank Jennifer Bricker-Bolton and Irene Manero for proofreading this manuscript and helping with the English language.

Funding: The authors declare that they have not received any funds or grants for this research.

Competing interests: The authors have no competing interests that are relevant to the content of this article.

Author Contributions: Dr. Júlia Candel-Pau conceptualized and designed the study, designed the data collecting instruments, designed and created the new neonatal color scale (Neomar), carried out the training of the staff in the use of the new scale, collected data, coordinated and supervised data collection, helped analyze the results of the study, drafted the initial manuscript, and approved the final manuscript as submitted. Dr. Silvia Maya-Enero helped design the study, collected data, coordinated and supervised data collection, helped analyze the results of the study, helped draft the initial manuscript, and approved the final manuscript as submitted. Dr. Jordi García-García helped in the initial study design, helped create the new neonatal color scale and collect data, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr. Xavier Durán performed all the statistical analyses and helped the team interpret them. He helped write the “Patients and methods” section and provided all the figures. He approved the final manuscript as submitted. Dr. Maria Ángeles López-Vílchez helped conceptualize and design the study, helped create the new neonatal color scale, collected data, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of our hospital (ref. 2015/6519/I).

Consent to participate: Parental informed consent was obtained from all individual participants included in the study.

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Transcutaneous bilirubin reliability during and after phototherapy depending on skin color

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