Transcutaneous Bilirubinometry in Healthy Term and Near-Term Neonates
Transcutaneous Bilirubinometry in Healthy Term and Near-Term Neonates
Objectives: Bilirubin measured by transcutaneous bilirubinometry (TcB) is a reasonably
 accurate estimate of serum total bilirubin (STB). Observational studies indicate that
 replacing clinical assessment of bilirubin (CaB) with TcB may result in reduced need for
 blood sampling for STB estimation. Objective of this study was to determine if routine use of
 transcutaneous bilirubinometry decrease the need for blood sampling for confirmation of STB
 in healthy term and near term neonates?

 Study design: Study was conducted as a randomized controlled trial at a tertiary care
 neonatal unit. Healthy neonates born at 35 or more completed weeks of gestation were eligible
 for enrolment if they had clinically evident jaundice during first week of life. In each
 enrolled neonate, level of jaundice was assessed by two methods - CaB followed by TcB
 (BiliCheck®, SpectRx Inc, Norcross, GA). By random allocation method, one of these estimates
 was used for deciding the need for blood sampling to confirm STB. Need for blood sampling was
 defined to be present if the bilirubin assessed by the allocated method exceeded 80% of
 age-specific cut-off for phototherapy as per American Academy of Pediatrics 2004 guidelines.
 Study had ethics clearance and written informed consent was obtained from parents.
Introduction/objectives: As the bilirubin concentration in the serum increases, it is
 deposited in the skin and subcutaneous tissues, producing the physical sign of jaundice.1
 There is a well-established relationship between the serum total bilirubin (STB)
 concentration and the intensity of jaundice in neonates.2 But variation in color perception
 by the human eye, differences in neonatal skin pigmentation, and variation in both the
 intensity and color of the available light affect the ability of an individual to estimate
 the STB by clinical assessment alone.3-10 Transcutaneous bilirubin (TcB) measured by
 spectrophotometry has positive and a linear correlation with STB, and therefore, is a useful
 screening tool to measure clinically significant jaundice.11-14 Newer devices such as
 BiliCheck® can even correct for the effect of skin pigmentation on TcB measurement and
 therefore are reported to have closer agreement with STB.15-17 American Academy of Pediatrics
 in its guidelines on management of hyperbilirubinemia in term and near-term neonates,
 cautions against relying on clinical assessment of severity of jaundice.18 Therefore, blood
 sampling for STB measurement is needed in a significant proportion of healthy clinically
 jaundiced neonates. As compared to clinical assessment TcB is thought to be a more accurate
 and objective estimate of STB, its use may decrease the need for blood sampling to measure
 STB. Observational and retrospective analyses have estimated that routine use of Tc
 bilirubinometry for jaundice assessment results in 34% to 80% reduction in need for blood
 sampling for STB measurement.19-21 Objective of this randomized clinical trial was to
 determine if routine use of transcutaneous bilirubinometry decrease the need for blood
 sampling for confirmation of STB in healthy term and near term neonates? In addition, we also
 assessed the correlation and agreement of TcB and CaB with measured STB.

 Methodology: Study was conducted as a randomized controlled trial in a tertiary care
 hospital. Neonates born at 35 or more completed weeks of gestation were eligible for
 enrolment if they developed clinical jaundice from 25 to 168 h of life. Neonates with Rh
 hemolytic disease, those requiring NICU admission for more than 24 h, having major congenital
 malformation or having received phototherapy were excluded. Study was carried out from
 November 1, 2006 to July 7, 2007 except in month of March 2007 when the primary investigator
 was not posted in clinical service area.

 A log book was maintained in delivery areas of the hospital to identify neonates born at 35
 or more weeks of gestation. Gestation was assigned based on 1st trimester ultrasound. In the
 event of non-availability of ultrasound report, gestation was assigned by date of last
 menstrual period and confirmed by Expanded New Ballard Score22 within 24 h of age. After
 receiving written informed consent from parents, the identified neonates were assessed every
 8-12 h for clinical jaundice. On identification of clinical jaundice, the primary
 investigator assigned a clinically assessed level of bilirubin (CaB). This assessment was
 performed in an adequately illuminated room. Skin was blanched by digital pressure, revealing
 underlying color of skin and subcutaneous tissue in five dermal zones (as described by
 Kramer). Both extent and intensity of yellowish discoloration was used to assign the CaB.
 Each clinical assessment was immediately followed by transcutaneous measurement of bilirubin
 (TcB). TcB was average of five sequential measurements at forehead obtained using BiliCheck®
 (SpectRx Inc, Norcross, GA). Clinical assessment always preceded the transcutaneous
 measurement to prevent primary investigator getting biased by the TcB value.

 We conducted a pilot study in our unit and found out that 15% neonates (≥35 wk gestation)
 undergo blood sampling for measurement of STB in first week of life (unpublished data).
 Sample size for a relative reduction of 40% in need for blood sampling (absolute reduction
 (from 15% to 9%), with a power of 80% and two-sided significance of 5% was 492 assessments in
 each group.

 By random allocation method, either CaB or TcB was used for deciding the need for blood
 sampling to measure STB. Need for blood sampling was defined to be present if the bilirubin
 assessed by the allocated method exceeded 80% of age-specific cut-off for phototherapy as per
 American Academy of Pediatrics 2004 guidelines.7 STB was measured using twin-beam
 spectrophometry (Gineveri, Italy). Neonates discharged before completing 72 h of age were
 brought to hospital for assessment of jaundice 24-72 h after discharge as per AAP
 recommendations. Up to three assessments conducted at least 12 h apart in a neonate could be
 included in the study. Such repetitive assessments were independently randomized irrespective
 of previous assignment. Randomized sequence was generated in fixed block size of six each
 using a web-based random number generator.The random codes were kept in serially numbered,
 opaque and sealed identical envelops. The envelope was opened after obtaining both CaB and
 TcB values. Chief investigator was unaware of the process of randomization.

 We were aware of the possibility of erroneously missing significant jaundice if baby did not
 qualify for sampling by the randomized method of assessment. To safeguard against such an
 occurrence, clinical team had an authority to take an over-riding decision to measure STB.
 Incidence of such 'overriding decisions' and their outcome in terms of need for phototherapy
 were recorded.

 We analyzed relationship between two methods of assessment of bilirubin: transcutaneous
 bilirubinometry (TcB) and clinical assessment of bilirubin (CaB) with serum total bilirubin
 (STB). This relationship is described as correlation and agreement of the two with STB.

 All base line and outcome data were recorded prospectively in a pre-tested proforma. The data
 were then entered in Epi infoTM version 3.3.2. The data were checked for completion,
 consistency and accuracy. For quality control ten percent of records were checked by an
 independent investigator on a random basis. Data were analyzed using Epi infoTM version
 3.3.2. and Stata software version 9.1. Group characteristics were compared with χ2 test and
 two-sample t-test for discrete and continuous variables respectively. P value of <0.05 was
 taken as statistically significant. Analysis was intention-to-treat. Correlation of STB
 values to TcB and CaB was determined by Pearson correlation analysis. We determined the
 limits of agreement that could be applied to the whole population by the statistical analysis
 described by Bland and Altman.

 The protocol was cleared by institutional Ethics Committee. Informed consent was taken from
 one of parents of enrolled infants.

 Keywords: jaundice, neonates, transcutaneous bilirubinometry, clinical assessment of
 bilirubin
Inclusion Criteria:

 -  Neonates born at 35 or more completed weeks of gestation with clinical jaundice and
 age between 25 to 168 hours

 Exclusion Criteria:

 -  Neonates with Rh hemolytic disease those requiring NICU admission for more than 24 h
 having major congenital malformation or having received phototherapy