Transcutaneous Bilirubinometry in Healthy Term and Near-Term Neonates
Condition: Hyperbilirubinemia
MeSH terms: Hyperbilirubinemia
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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
    

Intervention name(s): BiliChek (jaundice assessment); Transcutaneous bilirubinometry (TcB); Clinical asessment of bilirubin (CaB)
Intervention type(s): Device; Procedure; Other
Intervention description(s): assessment of jaundice was done by either transcutaneous bilirubinometry (TcB) method or by clinical assessment of bilirubin (CaB); transcutaneous bilirubinometry was used for jaundice assessment in healthy term and near-term jaundiced neonates between 24 to 168 hours of life; Clinical assessment of bilirubin (CaB) was used for jaundice assessment in healthy term and near-term jaundiced neonates between 24 to 168 hours of life
Other intervention name(s): BiliChek (transcutaneous bilirubin measuring device)
Intervention MeSH terms: Bilirubin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Diagnostic
Keywords: jaundice; neonates; transcutaneous bilirubinometry; clinical assessment of bilirubin