OBJECTIVE: The objective of this study was to provide data on transcutaneous bilirubin (TcB) levels for the first 120 postnatal hours and to develop an hour-specific TcB nomogram for healthy term and near-term neonates.
METHODS: From September 2005 to August 2008, we obtained 14864 TcB measurements from 2818 healthy neonates (gestational age ≥ 35 weeks and birth weight ≥ 2000 g). All measurements were performed with the BiliCheck bilirubinometer, at designated times from 12 to 120 postnatal hours. TcB percentiles for each designated time were calculated and used for the development of an hour-specific nomogram. TcB percentiles for neonates who required phototherapy are also presented.
RESULTS: The developed TcB nomogram reflects the natural history of TcB levels in healthy neonates up to the fifth postnatal day. A different pattern of TcB increasing rate was noted in neonates who did and did not require phototherapy but with substantial overlap of TcB values between the 2 groups.
CONCLUSIONS: We provide data on TcB levels for the first 120 postnatal hours from a large population of white, healthy, term and near-term neonates. We also present a percentile-based TcB nomogram designated for noninvasive and hour-specific evaluation of neonatal hyperbilirubinemia.
The widespread practice of early postnatal discharge mandates prompt detection and appropriate follow-up of neonates who are at risk for developing significant hyperbilirubinemia.1–7 Hour-specific nomogram evaluation of total serum bilirubin (TSB) and predischarge risk assessment by using the predictive nomogram developed by Bhutani et al8 has been proved effective in predicting this event4,6,7,9; however, determination of TSB levels remains an invasive and time-consuming procedure, which makes the implementation of a universal screening strategy particularly difficult. In these settings, technologic improvements in transcutaneous bilirubin (TcB) determination offered a promising perspective to health care professionals, because the new-generation devices have been proved reliable for estimating bilirubin concentration in neonates.10–19 Thus, TcB has been recommended by the American Academy of Pediatrics as a reasonable alternative to TSB for screening newborn infants with jaundice3,4,20; however, the clinical implication of this practice could be a matter of concern, because there are limited data regarding the natural history of TcB levels during the first days of life,21–23 and some reports suggested that it is incorrect to plot TcB levels on TSB-based nomograms.24 The purpose of this study was to provide data on TcB levels for the first 120 hours after birth in healthy term and near-term neonates and to develop a TcB nomogram designated for noninvasive and hour-specific bilirubin evaluation in neonates with jaundice.
The study was performed at the well-baby nursery of the University Hospital of Patras (Patras, Greece) from September 2005 to August 2008. All healthy term and near-term neonates with gestational age (GA) of ≥35 weeks and birth weight of ≥2000 g were eligible for enrollment in the study. Exclusion criteria were admission to the ICU, positive direct Coombs test, jaundice that required intervention during the first 24 hours, and glucose-6-phosphate dehydrogenase deficiency. Only newborns from Rh-negative mothers or those with positive indirect Coombs test were evaluated for blood group and direct Coombs test.
TcB determinations were made by multiwavelength spectrophotometry by using the BiliCheck bilirubinometer (SpectRx Inc, Norcross, GA). All measurements were obtained by properly trained physicians in adequately illuminated rooms and according to the standard described technique.10,11 During the first postnatal day, TcB determinations were performed at time intervals of 6 ± 2 hours and thereafter at intervals of 12 ± 2 hours up to the age of 120 hours. At least 5 measurements were obtained from each infant. The decision for phototherapy was made by the attending pediatrician on the basis of TSB levels and according to the guidelines presented by the American Academy of Pediatrics.4 Because our institution applies a discharge policy of ≥72 hours for vaginally delivered infants and ≥96 hours for those born by cesarean delivery, the parents were advised to return to the nursery for follow-up measurements between 96 and 120 hours of age. TcB values were recorded on a flow sheet designed for the study and attached to the medical file of each infant. Values that were obtained after the initiation of phototherapy were excluded.
The data were analyzed by using SPSS 15.0 for Windows (SPSS, Chicago, IL). TcB percentiles for each designated time were calculated, and these data were used for the design of an hour-specific nomogram with Microsoft Excel (Microsoft, Redmond, WA). TcB percentiles for the neonates who required phototherapy were also calculated and presented.
The study was approved by the ethics committee of the University Hospital of Patras. Any assignment of medical intervention (eg, noninvasive TcB measurements, decision for phototherapy) strictly adhered to the protocol applied in our institution for the management of neonatal jaundice. An informed consent was obtained from 1 of the parents.
During the study period, a total of 14864 TcB measurements were obtained from 2818 healthy term and near-term neonates. This sample emerged from a total of 4021 live births that took place in our institution during the same period, because 610 neonates did not meet the enrollment criteria and 593 infants failed to complete the follow-up for various reasons (eg, refusal of consent, inconvenient time of birth, earlier discharge, insufficient number of measurements). The mean birth weight was 3201 ± 440 g, and the mean GA was 270 ± 10 days (38 weeks, 4 days ± 1 week, 3 days). Population demographic data are presented in Table 1. Hyperbilirubinemia that required phototherapy was documented for 172 (6.1%) neonates.
The number of TcB measurements and TcB percentiles at designated times are presented in Table 2. A TcB nomogram with smoothed percentile curves drawn from the raw data is illustrated in Fig 1, whereas Fig 2 shows percentile TcB curves according to GA. For the development of these nomograms the data from neonates who required phototherapy were excluded.
In Fig 3, the 95th-, 75th-, and 50th-percentile TcB curves of the nomogram are presented in comparison with the 5th- and 50th-percentile TcB curves from neonates who were exposed to phototherapy. Only TcB values before the initiation of phototherapy were used. During the first 24 hours of age, the 5th-percentile TcB curve from neonates who required phototherapy rested constantly below the 75th-percentile TcB curve from those who did not require phototherapy, resulting in a substantial overlap of TcB values between the 2 groups (Fig 3). This overlap, although gradually ameliorated, is also present in the second postnatal day and partially noted up to the age of 60 hours. After this time point, the 5th-percentile TcB curve from neonates who required phototherapy exceeds the 95th-percentile TcB curve of the nomogram (Fig 3). Practically, at 24 hours, 61 (39.6%) TcB measurements from neonates who subsequently required phototherapy were below the 95th percentile and 14 (9.1%) were below the 75th percentile. In those neonates, 14.7% (n = 16) of the TcB measurements were also below the 95th percentile at 48 postnatal hours.
Early postnatal discharge of healthy neonates mandates the implementation of reliable but more flexible follow-up strategies for preventing subsequent severe hyperbilirubinemia. In this study, we sought to provide data regarding TcB levels for the first 120 hours of life in a white population of healthy term and near-term neonates. These data were subsequently used for the development of an hour-specific percentile-based TcB nomogram, which represents in fact the natural history of TcB levels up to the fifth postnatal day.
To our knowledge, 3 studies have been previously published about this topic. Sanpavat et al21 reported a nomogram that was based on TcB measurements that were obtained with the BiliCheck device from 284 term Thai neonates who were born by cesarean delivery. Maisels et al22 published a TcB nomogram for the first 96 hours of life that was based on measurements from 3984 healthy North American infants by using the Minolta Air-Shields JM-103 bilirubinometer (Draeger Medical Inc, Telford, PA). De Luca et al23 provided data on 2198 healthy, white, European neonates by using the BiliCheck device and presented a TcB nomogram for the first 96 hours of life.
There are important differences between our study and these reports, however. First, in this study, we provide data on a large homogeneous population of healthy neonates. The nomogram presented by Sanpavat et al21 was based on a small sample of term neonates who were born exclusively by cesarean delivery, whereas Maisels et al22 obtained data only from a small sample of neonates from 72 to 96 hours of age, and they also enrolled in their study infants with positive direct Coombs test. Second, unlike the aforementioned reports, our TcB measurements extended up to 120 hours of age. This was possible because of the postnatal discharge policy and the protocol for the management of neonatal jaundice applied in our institution, which made attainable a follow-up between 96 and 120 hours of age for the majority of infants. In this time interval, we obtained 2845 TcB measurements from 2265 neonates (80.4% of our study population), a clearly superior sample in comparison with the other reports. Third, De Luca et al23 as well as Sanpavat et al21 obtained TcB measurements with the BiliCheck device as we did, whereas Maisels et al22 used a different transcutaneous bilirubinometer. Fourth, we developed our nomogram by using TcB measurements exclusively from neonates who did not required phototherapy, as did Maisels et al,22 whereas De Luca et al23 included in their study data from neonates who required phototherapy. Finally, we developed a basic nomogram that was based on TcB measurements from the whole population, and we presented separately 2 TcB nomograms according to GA. The same approach was adopted by Maisels et al,22 whereas De Luca et al23 reported only 2 GA-specific TcB nomograms.
The 95th-percentile curve of the nomogram developed by Maisels et al22 rests constantly between the 95th- and 75th-percentile curves of our nomogram, whereas their 50th-percentile curve coincides with our 25th-percentile curve. This discrepancy could be mainly attributed to the use of different transcutaneous bilirubinometers. Conversely, the 95th-percentile curve of the nomogram presented by De Luca et al23 constantly exceeds our 95th-percentile curve, but their 50th-percentile curve is quite similar to ours. Because the latter investigators used the same device on a similar European neonatal population, we assume that this difference is because they included in their nomogram TcB values from neonates who required phototherapy.
In our study, ∼40% of the measurements from neonates who subsequently required phototherapy were below the 95th percentile at 24 hours, and 15% of the measurements in these infants were also below the 95th percentile at 48 hours (Fig 3). Thus, the 95th percentile track of the nomogram fails to differentiate reliably between infants who would and would not require phototherapy. Similarly, the 75th percentile cannot be considered as a reliable risk demarcator for subsequent significant hyperbilirubinemia, at least for the first 24 hours of life (Fig 3). Moreover, using the 75th percentile as high-risk demarcator, an inconveniently high percentage of neonates (25%) should be considered by definition as high risk for developing significant hyperbilirubinemia. Health care practitioners must be aware of this overlap of TcB values in the first postnatal hours between infants who would and would not require phototherapy.
This study has some potential limitations. We provide data that were obtained from a population of white neonates and from a single center, yet the new-generation transcutaneous bilirubinometers, such as the BiliCheck device, are shown not to be affected by the skin pigmentation and thus proved highly effective among heterogeneous populations.10–12,14,16,17; however, multicenter studies are needed for assessing the clinical applicability of the developed nomogram. Also, it should be mentioned that an important percentage (40.8%) of the neonates studied were born by cesarean delivery, and as many as 42.2% of the infants were exclusively formula fed. These factors, however, did not have a significant effect on the prevalence of significant hyperbilirubinemia and need for phototherapy (Table 1). Finally, we decided not to use TcB values from neonates who required phototherapy for the development of the nomogram because this would tend, if anything, to increase the 95th percentiles and would also complicate the interpretation of the observed overlap between TcB values from neonates who did and did not require phototherapy (Fig 3).
In this study, we provide data on the natural course of TcB levels for the first 120 postnatal hours, obtained from a large white population of healthy, term and near-term neonates. We also present a percentile-based TcB nomogram designated for noninvasive and hour-specific evaluation of neonatal hyperbilirubinemia, which may help health care professionals in the implementation of more flexible follow-up strategies for neonates with jaundice.
- Accepted July 18, 2009.
- Address correspondence to Sotirios Fouzas, MD, University Hospital of Patras, Department of Pediatrics, Rio, 265 04 Patras, Greece. E-mail:
Preliminary results of this study were presented at the second congress of the European Academy of Pediatrics; October 24–28, 2008; Nice, France.
Financial Disclosure: The authors have indicated they have no financial relationships relevant to this article to disclose.
What's Known on This Subject:
TcB represents a reasonable alternative to TSB for screening newborn infants with jaundice; however, there are limited data regarding the natural history of TcB levels during the first days of life.
What This Study Adds:
We provide data on the natural course of TcB levels for the first 120 postnatal hours and present a percentile-based TcB nomogram designated for noninvasive and hour-specific evaluation of neonatal hyperbilirubinemia in healthy term and near-term neonates.
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