ARTICLE. Jaundice Noted in the First 24 Hours After Birth in a Managed Care Organization

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1 ARTICLE Jaundice Noted in the First 24 Hours After Birth in a Managed Care Organization Thomas B. Newman, MD, MPH; Petra Liljestrand, PhD; Gabriel J. Escobar, MD Objective: To investigate the significance of jaundice noted in the first 24 hours after birth in a community setting. Design: Supplementary analyses of a nested casecontrol study. Setting: Northern California Kaiser Permanente Medical Care Program. Patients: Six hundred thirty-one randomly selected newborns (controls) and 140 cases with total serum bilirubin levels of 25 mg/dl (428 µmol/l) or higher from a cohort of newborns of at least 2000 g birth weight and at least 36 weeks gestational age, born between January 1, 1995, and December 31, Main Outcome Measures: Notations of jaundice in the medical record, timing and results of bilirubin testing, use of phototherapy, and development of bilirubin levels of 25 mg/dl or higher. Results: Among the controls, the cumulative probability of a notation of jaundice (corrected for early hospital discharge using survival analysis) was 2.8% within 18 hours and 6.7% within 24 hours. In these newborns, cumulative proportions that had bilirubin levels measured were 38% within 12 hours and 43% within 24 hours of when jaundice was first noted. About 40% of bilirubin levels measured within 24 hours were above the estimated 95th percentile for age. Compared with newborns not noted to be jaundiced on the first day, newborns noted to be jaundiced within 24 hours were more likely to receive phototherapy (18.9% vs 1.7%; relative risk, 10.1; 95% confidence interval, ) and to develop a bilirubin level of 25 mg/dl or higher (odds ratio, 2.9; 95% confidence interval, ), but the absolute risk increase for total serum bilirubin levels of 25 mg/dl or higher was 0.2%. Conclusion: Jaundice noted in the medical record in the first 24 hours after birth was uncommon and often clinically significant in this setting, but other factors also need to be considered in determining its importance. Arch Pediatr Adolesc Med. 2002;156: From the Departments of Epidemiology and Biostatistics (Drs Newman and Liljestrand) and Pediatrics (Dr Newman), School of Medicine, The University of California, San Francisco; Division of Research, Kaiser Permanente Medical Care Program, Oakland (Drs Newman, Liljestrand, and Escobar); and Department of Pediatrics, Kaiser Permanente Medical Center, Walnut Creek (Dr Escobar), Calif. JAUNDICE APPEARING in the first 24 hours after birth is generally regarded as abnormal, necessitating at least a measurement of the total serum bilirubin (TSB) level. For example, the American Academy of Pediatrics practice guideline for treatment of hyperbilirubinemia in newborns states:...[j]aundice occurring before age 24 hours is generally considered pathologic and requires further evaluation. 1(p560) A more recent commentary reiterated this recommendation: Any infant who is jaundiced before 24 hours requires a measurement of the serum bilirubin level... 2(p764) In at least 1 widely publicized medical malpractice case, 3 failure to measure a bilirubin level in a newborn documented to have been jaundiced at 17 hours after birth was one of the allegations of negligence. However, available evidence suggests that jaundice by 24 hours is common. Davidson et al 4 observed jaundice in the first 24 hours in 25% of newborns, despite examining them only once per day. To examine the newborns for jaundice, they applied a tongue depressor with considerable force to the mucous membrane of the lower jaw and...skin of the forehead or the chin, 4(p962) a procedure that they state often revealed jaundice that was otherwise not apparent. Using this technique, jaundice was visible in 80% of newborns when TSB levels exceeded 6 mg/dl (103 µmol/l). More recently, Alpay et al 5 found that 41% of newborns had TSB levels of 6 mg/dl or higher at a mean of 17 hours after birth, Stevenson et al 6 found that 25% of newborns had these levels at 21 hours, and Carbonell et al 7 found that 47% of newborns had such levels at

2 hours. These results suggest that if it were carefully sought at about 24 hours, the finding of jaundice would be far too common to be considered pathologic. On the other hand, in clinical (as opposed to research) settings, where examination for jaundice is less systematic, the observation of jaundice at less than 24 hours could be more unusual and, hence, of greater clinical significance. Newborns noted to be jaundiced at less than 24 hours in clinical settings might be more likely to have been jaundiced for several hours before jaundice was noted, have pronounced jaundice, or have risk factors for jaundice that led to a careful examination for it. This study focuses not on jaundice that might have been noticed if the newborns had been closely examined at the right time but on jaundice that actually was noticed (and recorded in the medical record) in the course of routine care of newborns in a nonacademic, community setting. Specifically, we wanted to answer the following questions in that setting: (1) How often is jaundice noted in the medical record in term and near-term newborns less than 24 hours old? (2) How soon after a notation of jaundice is a TSB level measured? (3) When TSB levels are measured in the first 24 hours after birth, how high are they? (4) How strongly does jaundice noted in the first 24 hours after birth predict the eventual use of phototherapy? and (5) How strongly does jaundice in the first 24 hours predict the risk of developing a very high ( 25 mg/dl [ 428 µmol/l]) TSB level? METHODS STUDY DESIGN We expanded a previously reported nested case-control study 8,9 of newborns born between January 1, 1995, and December 31, 1996, to include newborns born between January 1, 1997, and December 31, We identified cases and controls using electronic hospitalization and laboratory records. Depending on the study questions (in the previous paragraph), we used data from the control group only (questions 1, 2, and 4), from all those in the entire birth cohort who had TSB levels measured in the first 24 hours (question 3), or from both cases and controls (question 5). STUDY SUBJECTS Subjects for this study came from 2 cohorts: a group of 73 cases and 423 controls born during 1995 and and a second group of 67 cases and 208 controls born during 1997 and 1998, totaling 140 cases and 631 controls. The cohort included newborns born at 11 Kaiser Permanente Medical Care Program hospitals in northern California, and the cohort included newborns born at any of these hospitals or on the Kaiser Permanente Medical Care Program service of another affiliated outside hospital, the Alta Bates Medical Center, Oakland. Both cohorts included only newborns of at least 36 weeks gestational age and at least 2000 g birth weight. Cases were newborns with a TSB level of 25 mg/dl or higher in the first 30 days after birth, excluding 1 newborn with conjugated hyperbilirubinemia (defined as a maximum conjugated bilirubin level 15% of the maximum TSB level; the excluded newborn s maximum conjugated bilirubin level was 50.9 mg/dl [870 µmol/l] and his maximum TSB level was 54 mg/dl [923 µmol/l]). Controls were randomly selected from the same 2-year birth cohorts as the cases. The ratio of cases to controls differed between the 2 cohorts because the subjects were identified primarily for a follow-up study of neurodevelopmental outcome at age 5, for which the high expense per subject precluded a higher case-control ratio. NOTATIONS OF JAUNDICE AND MEDICAL RECORD REVIEW Medical record analysts abstracted data from paper charts on the timing of the appearance of jaundice, as one of many items abstracted from newborn records. Although there were minor interhospital differences, all hospitals used a flow-sheet format to record the color of the newborn and other observations over time. Typically, nurses would record the newborn s color, vital signs, and other physical examination results with the date and time, using abbreviations such as P for pink color, J for jaundiced, and sl J for slightly jaundiced. After the first few hours of life, this typically occurred once per 8-hour shift. Therefore, it is possible, depending on the newborn s time of birth, that the color might not be checked between 18 and 24 hours after birth. The variable of interest for this study is thus the time jaundice was first noted in the medical record, not the time jaundice was first present or observed. In some cases after jaundice was first noted, it was not noted by some subsequent examiners, but we systematically collected data only on the time jaundice was first recorded. When the time was missing from the first notation of jaundice, medical record analysts used their best judgment based on times of preceding and succeeding observations to estimate the time of the observation. To assess reliability of the medical record abstraction, a second medical record analyst blindly reabstracted a random sample of 25 medical records. For 15 newborns, neither analyst found a notation of jaundice; for 7, both recorded the same date and time jaundice was first noted; and for the other 3, 1 found a notation of jaundice that the other did not. The agreement for whether jaundice was noted by 24 hours after birth was 23 of 25 (92%; expected agreement, 68%; =0.75). In some of the hospitals during some years of the study, jaundice meters (Minolta-Air Shields, Hatboro, Pa) were used for transcutaneous estimation of bilirubin levels. Results were generally recorded on nursing flow sheets and were abstracted by medical record analysts. However, use of jaundice meters was discretionary, and medical records did not generally indicate why they were used, when they were done, or how the results were interpreted. Because the availability of a jaundice meter could affect whether a jaundice notation was made and the timing of subsequent measurements of TSB levels, we stratified newborns into those who were and were not born in hospitals that used jaundice meters during that newborn s year of birth and compared results across these strata to estimate possible effects of use of jaundice meters on the results. BILIRUBIN LEVELS As previously reported, 10 all bilirubin levels with the date and time of specimen collection were obtained from the Northern California Regional Interlaboratory Information System. Total serum bilirubin levels were measured using the Kodak Ektachem (Eastman Kodak Co, Rochester, NY) (83%) or the Automated Chemical Analyzer (DuPont, Wilmington, Del) (13%) neonatal bilirubin assay or the Kodak Ektachem adult bilirubin assay (3%). STATISTICAL ANALYSIS Because about 25% of the newborns were discharged from the birth hospitalization before 24 hours, we used the Kaplan- Meier method for depicting graphic and descriptive statistics 1245

3 Proportion Noted to Be Jaundiced Age, h Figure 1. Kaplan-Meier survival estimate of cumulative proportion (of control newborns) noted to be jaundiced, censored at age of discharge. In these newborns, cumulative proportions who had a bilirubin level measured were 38% within 12 hours and 43% within 24 hours of when jaundice was first noted. on the timing of first notations of jaundice to account for censoring at the time of the initial hospital discharge. This method allows a newborn who was hospitalized for only 18 hours to contribute data on the risk of jaundice up to 18 hours, but beyond 18 hours, that newborn is censored, ie, removed from the denominator. For bivariate analyses, on the other hand, we considered whether jaundice was noted before 24 hours to be a dichotomous variable, regardless of the newborn s length of hospital stay. Statistical significance of bivariate comparisons was tested using 2 tests. We estimated relative risks (RRs) and odds ratios (ORs) using the Mantel-Haenszel method, stratifying on birth cohort ( vs ) to take into account the differing case-control ratios. 11 Because we had data on use of phototherapy in the entire groups of control newborns who were and were not noted to be jaundiced at less than 24 hours, we calculated the RR for use of phototherapy directly. To assess the risk of TSB levels of 25 mg/dl or higher, a much rarer outcome, we used the case-control design, from which the RR cannot be directly calculated but is approximated by the OR. The nested case-control design also allows calculation of the absolute risk of TSB levels of 25 mg/dl or higher in those who were and were not noted to be jaundiced at less than 24 hours by assuming that the findings in the 631 controls are representative of all newborns who did not become cases. The numbers for a 2-by-2 table for the entire cohort are thus obtained from those of the nested case-control study by dividing the number of controls by the sampling fraction (in this study, 631/105244). We used Stata 6.0 (Stata Corp, College Station, Tex) for all statistical analyses. RESULTS Within the randomly selected control group, 37 newborns had a notation of jaundice in the first 24 hours after birth. Using the Kaplan-Meier method to account for hospital discharges at less than 24 hours, the cumulative probability of a notation of jaundice in the medical record was 1% by 12 hours, 2.8% by 18 hours, and 6.7% by 24 hours. Beginning at about 16 hours after birth, the proportion of newborns noted to be jaundiced rises rapidly (Figure 1). Of the 631 controls, 7 had positive direct antiglobulin test (DAT) results, 130 had negative DAT results, and, in 494, a DAT was not done. Excluding the Table 1. Characteristics of Control Newborns and Notations of Jaundice in the Medical Record in the First 24 Hours After Birth* Characteristic Jaundice at 24 h (n = 37) No Jaundice at 24 h (n = 594) Ethnicity White 17 (45.9) 278 (46.8) Latino 12 (32.4) 122 (20.5) Asian 6 (16.2) 107 (18.0) Black 2 (5.4) 65 (10.9) Other or unknown 0 (0) 22 (3.7) Sex Male 20 (54.1) 323 (54.4) Female 17 (45.9) 271 (45.6) Gestational age, wk (91.9) 534 (89.9) 38 3 (8.1) 60 (10.1) Breastfeeding Breastfed only 20 (54.1) 374 (63.0) Any bottle feeding 17 (45.9) 220 (37.0) Cephalhematoma Noted 2 (5.4) 25 (4.2) Not noted 35 (94.6) 569 (95.8) Bruising Noted 7 (18.9) 69 (11.6) Not noted 30 (81.1) 525 (88.4) Birth cohort (78.4) 394 (66.3) (21.6) 200 (33.7) Jaundice meter reading facility Yes 15 (40.5) 276 (46.5) No 22 (59.5) 318 (53.5) P Value *Data are given as number (percentage) unless otherwise indicated. Some percentages do not sum to 100 because of rounding. Indicates whether the newborn was born at a facility that was using jaundice meter readings at some time during the newborn s year of birth. 7 newborns with positive DAT results (none of whom were first noted to be jaundiced hours after birth) did not affect the results depicted in Figure 1. If, in addition to newborns with notations of jaundice in the medical record, we count newborns who had a TSB level measured in the first 24 hours as having been noted to be jaundiced at that time, these proportions are increased by about 1%, to 1.8% by 12 hours, 3.8% by 18 hours, and 7.9% by 24 hours. Jaundice at less than 24 hours was not statistically significantly associated with ethnicity, sex, gestational age, breastfeeding, bruising, cephalhematomas, birth cohort, or being born in a hospital using jaundice meter readings (Table 1). Because DATs and blood type testing on newborns were done selectively (eg, on jaundiced newborns), we could not assess the effect of apparent isoimmunization on notations of jaundice. Notations of jaundice in the medical record at less than 24 hours after birth did not trigger immediate measurement of TSB levels. Among the 37 control newborns noted to be jaundiced before 24 hours, only 7 (19%) had a TSB level measured within 6 hours of when jaundice was first noted in the medical record and only 14 (38%) had a TSB level measured within 12 hours. In 3 (8%), a TSB level was measured after 12 hours, and in 13 (35%), no TSB level was recorded. These results did

4 not differ by the age at which jaundice was first noted ( 18 hours vs hours) or by whether the newborns had a jaundice meter reading (Table 2). How high were TSB levels in these newborns? The average TSB level for the 7 control newborns with jaundice notations at less than 24 hours and TSB levels measured within 6 hours of the notation was 7.4 mg/dl (127 µmol/l) (range, mg/dl [ µmol/l]). In the entire cohort of newborns, 3479 (3%) had TSB levels obtained before 24 hours. Presumably, many of Table 2. Total Serum Bilirubin (TSB) Measurements Within 12 Hours in Control Newborns Noted to Be Jaundiced in the First 24 Hours After Birth Total No. TSB Sent Within 12 h, No. (%) Jaundice noted At 18 h 20 7 (35.0) At h 17 7 (41.2) Birth cohort (41.4) (25.0) Newborn had jaundice meter reading done Yes 9 2 (22.2) No (42.9) P Value these were done for early jaundice. To estimate the proportion of these newborns with TSB levels above the 95th percentile, we assumed a linear increase in the 95th percentile of TSB levels during the first 24 hours, from about 2 mg/dl (34 µmol/l; the approximate 95th percentile for TSB levels in cord blood 12,13 ) to 8 mg/dl (137 µmol/l; the approximate 95th percentile at 24 hours 5,6 ) (Figure 2). This line closely matches the linear increase in the 95th percentile for TSB levels between 18 and 36 hours reported by Stevenson et al. 6 Of the 3479 newborns who had TSB measurements in the first 24 hours, 1460 (42%) had TSB levels above this 95th percentile line. Although most newborns noted to be jaundiced in the first 24 hours after birth did not receive any treatment, such newborns were more than 10 times as likely to be treated with phototherapy as newborns not noted to be jaundiced on the first day (18.9% vs 1.7%; Mantel- Haenszel RR, 10.1; 95% confidence interval [CI], ) (Table 3). Of the newborns in the control group who received phototherapy, a significant number (41%) had been noted to be jaundiced at less than 24 hours. Among the control newborns noted to be jaundiced at less than 24 hours, those who did not have a TSB measurement within 12 hours of when jaundice was noted were less likely to receive phototherapy than those whose TSB level was measured within 12 hours (2/23 cases vs TSB, mg/dl Age, h Figure 2. First total serum bilirubin (TSB) levels measured at less than 24 hours after birth. Newborns with positive direct antiglobulin test results are indicated by plus signs. The line is at the estimated 95th percentile. About 40% of bilirubin levels measured within 24 hours were above the estimated 95th percentile for age. To convert TSB from milligrams per deciliter to millimoles per liter, multiply by

5 Table 3. Relation Between Notation of Jaundice in the First 24 Hours After Birth and Use of Phototherapy in Control Newborns* Subgroup Phototherapy No Phototherapy Total Jaundice at 24 h 7 (18.9) 30 (81.1) 37 No jaundice at 24 h 10 (1.7) 584 (98.3) 594 Total 17 (2.7) 614 (97.3) 631 *Data are given as number (percentage). 5/14 controls; Mantel-Haenszel RR, 0.16; 95% CI, ). Newborns noted to be jaundiced at less than 24 hours were also more likely to develop TSB levels of 25 mg/dl or higher, although the RR was smaller than that for use of phototherapy (Mantel-Haenszel OR, 2.9; 95% CI, ) (Table 4), and only 14% of the cases of TSB levels of 25 mg/dl or higher had that risk factor. Among the newborns noted to be jaundiced at less than 24 hours, those who did not have a TSB measurement within 12 hours of when jaundice was noted were not at significantly increased risk of developing TSB levels of 25 mg/dl or higher (12/20 cases vs 23/37 controls; Mantel- Haenszel OR, 0.78; 95% CI, ). The absolute risk of developing a TSB level of 25 mg/dl or higher was about 0.32% among those jaundiced in the first 24 hours, compared with about 0.12% among those who were not, an absolute risk increase of 0.2%. COMMENT Table 4. Relation Between Notation of Jaundice in the First 24 Hours After Birth and Total Serum Bilirubin (TSB)* Cases (TSB 25 mg/dl) Controls Total Nested Case-Control Study Jaundice at 24 h 20 (14.3) 37 (5.9) 57 No jaundice at 24 h 120 (85.7) 594 (94.1) 714 Total 140 (100) 631 (100) 771 Entire Cohort Jaundice at 24 h 20 (0.32) 6171 (99.68) 6191 No jaundice at 24 h 120 (0.12) (99.88) Total 140 (0.13) (99.87) *Data are given as number (percentage). We found that notations of jaundice at less than 24 hours after birth in this population were uncommon, occurring in only 6.7% of newborns. Contrary to published guidelines, 1,2 newborns in whom jaundice was noted at less than 24 hours did not generally receive immediate measurements of TSB levels, although when these levels were measured, they were often high. Compared with newborns not noted to be jaundiced on the first day, newborns noted to be jaundiced at less than 24 hours were more than 10 times as likely to be treated with phototherapy, but only about 3 times as likely to develop a TSB level of 25 mg/dl or higher, an increase in absolute risk of 0.2%. Our finding that fewer than 10% of newborns had notations of jaundice in their medical records in the first 24 hours after birth is not inconsistent with data suggesting that about 40% of newborns 18 to 24 hours old have bilirubin levels at which jaundice can be discerned if carefully sought. 4-6 Whether jaundice is noted in the medical record at less than 24 hours depends on the age at which newborns are checked for it, sensitivity of the examination, and completeness of charting. Many newborns in this study are likely not to have been examined at 20 to 24 hours after birth, and few are likely to have been examined as rigorously as in the study by Davidson et al. 4 Furthermore, even if jaundice had been seen, it is not clear that it would have been noted in the medical record until the next time vital signs and other physical examination items were due. If nurses had systematically checked all newborns for jaundice using the technique used by Davidson et al 4 at close to age 24 hours and charted the results, many more newborns would likely have been noted to be jaundiced. This increase in sensitivity, however, would come at the expense of specificity many more normal newborns would have been identified. The shape of the Kaplan-Meier plot of cumulative probability of jaundice notations is also consistent with findings of previous studies. The curve starts to rise much more steeply at about 16 to 18 hours, consistent with this being the age at which jaundice first begins to appear in a few normal newborns, presumably those whose TSB levels or visibility of jaundice is at the higher end of the normal distribution. In contrast, the flatness of the curve at less than 16 to 18 hours after birth suggests that such early jaundice is rare and, hence, more likely to be pathologic. The increase in slope at about 16 hours did not appear to be attributable to newborns with positive DAT results, nor was it explainable by selective discharge of nonjaundiced newborns. Because only 25% of newborns were discharged at less than 24 hours, loss of subjects from the denominator could explain (at most) a 33% increase in notations of jaundice before 24 hours, whereas a 320% increase (from 1.6% at 16 hours to 6.7% at 24 hours) was observed. Many newborns with notations of jaundice in their medical records at less than 24 hours after birth did not have bilirubin levels measured, a departure from the American Academy of Pediatrics practice guideline. 1 Cabana et al 14 reviewed reasons for nonadherence to practice guidelines. Lack of awareness and lack of familiarity with the guideline seem possible, because until the recent alert from the Joint Commission on Accreditation of Healthcare Organizations, 15 the need to measure TSB in newborns jaundiced in the first 24 hours had not received widespread attention. Lack of outcome expectancy (that a bad outcome will occur if the guideline is not followed) is also possible, because hyperbilirubinemia severe enough to consider exchange transfusion is rare 10 and kernicterus is more rare. 16 Although all that is required is ordering a blood test (already done routinely in 18%-52% of newborns in these hospitals 10 ), external barriers and inertia are also possible factors, particularly regarding policy changes such as allowing nurses to order TSB levels in these 1248

6 newborns without a physician s order, as has been recommended by Johnson et al. 17 Another possibility is lack of agreement with the guideline. The American Academy of Pediatrics 1 recommendation to check the TSB level in any newborn jaundiced at less than 24 hours after birth does not discriminate between mild and more severe jaundice, nor between jaundice noted at close to 24 hours and jaundice apparent earlier on the first day of life. As already discussed, mild jaundice at 24 hours is normal. It is possible that clinicians caring for the newborns in this study believed that timing and severity of jaundice or other factors may be used to decide whether jaundice is significant enough to warrant TSB testing. The high proportion of newborns in the entire cohort whose TSB levels were measured at less than 24 hours who had levels above the 95th percentile supports the hypothesis that clinicians measured TSB levels selectively at this age. On the other hand, weak evidence against this hypothesis is that, in the much smaller sample for whom we know the time jaundice was first noted in the medical record, we did not find that newborns noted to be jaundiced at less than 18 hours after birth were more likely to have TSB levels measured within 12 hours than those whose jaundice was first noted at 18 to 24 hours. Finally, 2 other possible reasons why bilirubin levels were not obtained are worth considering. First, the pediatricians caring for the newborns may not have been aware of nursing notes indicating jaundice. Second, they might not have agreed with the nurse s assessment that the newborn was jaundiced. Unless the TSB level is 12 mg/dl (205 µmol/l) or higher, there is considerable interobserver disagreement on whether jaundice is present or absent. 18,19 Especially if the initial observation was made under suboptimal conditions (eg, at night under incandescent lights), a pediatrician examining the newborn and noting no jaundice might conclude that the initial assessment was in error. The 10-fold higher use (compared with newborns not noted to be jaundiced on the first day) of phototherapy in newborns noted to be jaundiced at less than 24 hours provides evidence to support measuring TSB levels in these newborns and observing them closely. The fact that the RR (2.9) for TSB levels of 25 mg/dl or higher is much lower than that for use of phototherapy may reflect the efficacy of phototherapy at attenuating the risk associated with early jaundice. Presumably, if more newborns with early jaundice had been observed closely and treated with phototherapy at lower levels, the RR of TSB levels of 25 mg/dl or higher would have been further attenuated. Our results point in 2, somewhat conflicting, directions. On the one hand, notations of jaundice at less than 24 hours were uncommon and were associated with high TSB levels, a higher risk of TSB levels of 25 mg/dl or higher, and markedly increased use of phototherapy. This suggests that jaundice at less than 24 hours is clinically relevant. On the other hand, the absolute increase in risk of TSB levels of 25 mg/dl or higher in newborns jaundiced at less than 24 hours was low (approximately 2/1000), despite poor adherence to the recommendation that all such newborns have a TSB level measured. This suggests that notations of jaundice at less than 24 hours are often of little significance. This latter position is supported by the observation that newborns who did not have a TSB level promptly measured were not at higher risk of subsequent TSB levels of 25 mg/dl or higher, and by data from the literature suggesting that 25% to 50% of newborns 18 to 24 hours after birth have TSB levels at which jaundice can be appreciated. 3-7 Perhaps the best interpretation of these results is that newborns noted to be jaundiced at less than 24 hours after birth do not represent a homogeneous group. The actual time of onset and severity of jaundice, sensitivity of the observer, clinical context, and evolution of jaundice over time provide additional information that determines the relevance of an observation of jaundice at less than 24 hours. Should all newborns jaundiced at less than 24 hours after birth have a bilirubin measurement? If we want to make a blanket statement that jaundice before a certain age is pathologic until proven otherwise, this study and others 3-7 suggest that that age would be closer to 16 than to 24 hours. On the other hand, because the time when jaundice is first observed on a busy newborn service is likely to be later than its time of onset (because of variability in timing of examinations and in observers ability to discern jaundice) and because of the rare but potentially devastating consequences of missing early jaundice, 17 a policy of measuring bilirubin levels in newborns jaundiced at less than 24 hours seems reasonable. Need the bilirubin measurement be a TSB level, or would a transcutaneous measurement of bilirubin suffice? Results of transcutaneous bilirubin measurements are generally within 2 to 3 mg/dl (34-51 µmol/l) of those obtained by high-pressure liquid chromatography 20,21 or standard laboratory methods. 22 This means that if the TSB level is 6 mg/dl (103 µmol/l), the transcutaneous value is likely to be between 3 mg/dl (51 µmol/l [below the 40th percentile at 24 hours]) and 9 mg/dl (154 µmol/l [well above the 95th percentile]), an unimpressive level of accuracy. However, the accuracy of standard laboratory measurements of TSB levels in this range compared with high-pressure liquid chromatography results is only a little better, 21 and there is wide interlaboratory variability in TSB measurements in clinical laboratories. 21,23,24 Therefore, there is not a strong basis to recommend one method of bilirubin measurement over the other both give only approximate estimates of the TSB level. As is the case with interpreting jaundice in the first 24 hours after birth, measurements of bilirubin level also need to be considered in context. Accepted for publication August 6, This study was supported by a grant from The David and Lucile Packard Foundation, Los Altos, Calif; grant R01 NS39683 from the National Institute of Neurological Disorders and Stroke, Bethesda, Md; and grant M01 RR01271 from the National Institutes of Health, Pediatric Clinical Research Center, San Francisco, Calif. None of the funding organizations had any role in the design, conduct, interpretation, or analysis of this study. This study was presented at the meeting of the Pediatric Academic Societies, Baltimore, Md, May 7,

7 What This Study Adds Jaundice in the first 24 hours after birth is often considered pathologic, but studies in research settings have found that bilirubin levels at which jaundice is discernible occur in 25% to 50% of term newborns by 24 hours. The frequency and significance of jaundice noted in the first 24 hours after birth in community settings are not known. Medical chart reviews in a large managed care organization revealed that about 7% of newborns were noted in the medical record to be jaundiced in the first 24 hours of life. Most did not have bilirubin levels measured within 24 hours of when jaundice was noted, but when levels were measured, they were often high (40% above the 95th percentile). Compared with newborns not noted to be jaundiced on the first day, newborns noted to be jaundiced at less than 24 hours were 10 times as likely to receive phototherapy and about 3 times as likely to develop bilirubin levels of 25 mg/dl (428 µmol/l) or higher, but the absolute risk increase was about 0.2%. These findings suggest that in this setting jaundice recorded in the medical record at less than 24 hours after birth was often clinically significant, but that other factors also need to be considered in determining its importance. We thank M. Jeffrey Maisels, MB, BCh, for general encouragement and suggestions on the manuscript; Blong Xiong, MPH, for programming; and Carol Viera, Darmell Brown, Rowena Allison, and Frances Sheykhzadeh, for medical record review. Corresponding author: Thomas B. Newman, MD, MPH, Department of Epidemiology and Biostatistics, The University of California, San Francisco, Campus Box 0560, San Francisco, CA ( newman@epi.ucsf.edu). REFERENCES 1. 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