Hyperbilirubinemia Clinical Trial
Official title:
Routine Use of Transcutaneous Bilirubinometry Reduces the Need for Blood Sampling in Neonates With Jaundice
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
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Diagnostic
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