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OBJECTIVE: To obtain transcutaneous bilirubin (TcB) measurements, at 6-hour intervals, in the first 96 hours after birth in a normal newborn population (gestational age: > or =35 weeks). METHODS: We performed 9397 TcB measurements on 3984 healthy newborn infants (gestational age: > or =35 weeks) from 6 to 96 hours of age. All measurements were performed in the well-infant nursery with a Draeger Air-Shields transcutaneous jaundice meter (model JM-103), within 2 hours of the designated time. RESULTS: There was a distinct pattern to the velocity of the increase in TcB levels over different time periods. TcB levels increased in a linear manner most rapidly in the first 6 to 18 hours and then less rapidly from 18 to 42 hours, followed by a much slower increase until peak levels occurred. Decreasing gestational age was associated significantly with higher TcB levels. CONCLUSIONS: We provide data on neonatal bilirubinemia, based on TcB levels determined in a large, predominately white and breastfed, North American population. Infants who require closer evaluation and observation initially are those whose bilirubin levels are > or =95th percentile, ie, increasing more rapidly than 0.22 mg/dL per hour in the first 24 hours, 0.15 mg/dL per hour between 24 and 48 hours, and 0.06 mg/dL per hour after 48 hours. These data should be useful for detecting aberrant trends, identifying infants who need additional evaluation, and planning appropriate follow-up for jaundiced newborns. [ABSTRACT FROM AUTHOR]

Competing Interests: FINANCIAL/CONFLICT OF INTEREST DISCLOSURES: Dr Newman reported providing expert witness consultation in medical malpractice litigation. Dr Maisels reported providing expert witness review and testimony in kernicterus medical malpractice litigation. Dr Watchko disclosed a financial relationship with McGraw Hill. Dr Grout reported receiving grant funding from Pfizer for a non-pediatric study. Dr Bogen disclosed a Board of Directors relationship with Mid-Atlantic Mothers’ Milk Bank. No other disclosures were reported., (Copyright © 2022 by the American Academy of Pediatrics.)

A review of the literature demonstrates that severe total hyperbilirubinemia (total serum bilirubin ≥ 20 mg/dL [340 µmol/L]) in some cholestatic term (≥37 weeks) and late-preterm (≥34 0/7 -36 6/7 weeks) gestation neonates poses a risk for bilirubin-induced brain damage. When the direct bilirubin fraction is <50% of the total serum bilirubin this risk is associated with the total serum bilirubin alone and treatment decisions should be based on the total serum bilirubin. On the other hand, there are limited data on the risk of bilirubin-induced brain damage in the neonate with severe total hyperbilirubinemia and a direct bilirubin fraction that is equal to or exceeds 50% of the total serum bilirubin. When this rare combination occurs, efforts to keep the indirect bilirubin fraction from reaching severe levels might, nevertheless, be prudent., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Objective: Due to selection bias and other issues, the only available serum bilirubin-based nomogram does not reflect the natural history of early neonatal bilirubinemia. Our objective was to obtain a global picture of the natural history of early post-natal bilirubin trajectories., Study Design: We pooled readings from 19 published transcutaneous bilirubin nomogram reports including many newborns at multiple sites. We constructed a universal transcutaneous bilirubin nomogram which included the 25th, 50th, 75th, and 95th percentiles from 12 to 120 h., Results: The global transcutaneous bilirubin nomogram included >119,000 readings from 44,392 apparently normal, predominantly breastfed newborns ≥35 weeks gestation. The pooled transcutaneous bilirubin trajectories increased during the first 3 post-natal days, and peaked or plateaued between the 3rd and 4th days., Conclusions: We provide the first globally derived transcutaneous bilirubin nomogram that reflects the natural history of early neonatal bilirubinemia in neonates ≥35 weeks gestation.

We measured end-tidal CO levels in 50 jaundiced newborns readmitted for phototherapy at age 54-244 hours. The median end-tidal CO level was 1.55 ppm, suggesting that hemolysis is not the primary contributor to the hyperbilirubinemia in many readmitted newborns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A breakthrough discovery 60 years ago by Cremer et al. has since changed the way we treat infants with hyperbilirubinemia and saved the lives of millions from death and disabilities. "Photobiology" has evolved by inquiry of diverse light sources: fluorescent tubes (wavelength range of 400-520 nm; halogen spotlights that emit circular footprints of light; fiberoptic pads/blankets (mostly, 400-550 nm range) that can be placed in direct contact with skin; and the current narrow-band blue light-emitting diode (LED) light (450-470 nm), which overlaps the peak absorption wavelength (458 nm) for bilirubin photoisomerization. Excessive bombardment with photons has raised concerns for oxidative stress in very low birthweight versus term infants treated aggressively with phototherapy. Increased emphasis on prescribing phototherapy as a "drug" that is dosed cautiously and judiciously is needed. In this historical review, we chronicled the basic to the neurotoxic components of severe neonatal hyperbilirubinemia and the use of standardized interventions.

Purpose: To examine what proportion of caregivers, if given a choice, would choose medical versus surgical treatment of appendicitis and what factors would be important in their decision., Methods: A survey was devised and given to the caregivers of children presenting to the pediatrician for a routine visit in community and academic pediatric clinics. The survey presented a summary of outcomes after medical (non-operative) and surgical treatment of uncomplicated appendicitis. Participants were then asked to choose medical versus surgical treatment if their child were to develop appendicitis. They were also asked to rate the importance of certain factors in their decision -1 being "not important" and 5 being "very important"., Results: Four hundred surveys were distributed with an 86.2% (345/400) response rate. Six percent (21/342) of respondents reported a history of appendicitis and 49.4% (168/340) reported having known someone who had appendicitis. The majority of respondents, 85.3% (284/333), were mothers. A minority of respondents, 41.7% (95% CI: 36.7, 47.0), chose medical treatment over surgery for appendicitis. There was no statistical difference in the proportion of mothers (41.6%) versus fathers who chose medical treatment (41.3%). Caregivers who chose medical treatment were more likely to rate time in hospital (p = .008) and time out of school (p = 05) as important in decision making when compared with those who chose surgery. Those who chose surgical treatment were more likely to rate risk of recurrent appendicitis (p < .001) as important to decision making. In the multivariate analysis, those who rated time in hospital as very important had more than twice the odds of choosing medical therapy (OR 2.20, p = 0.02) when compared with those who rated it as less important. Not knowing someone who has had appendicitis was significantly associated with choosing medical therapy when compared with those who do know someone who has had appendicitis, OR 2.3, p = .002. Rating pain as very important was also significantly associated with choosing medical therapy, when compared to those rating pain 1-3, OR 3.38, p = .03., Conclusions: In this survey of caregivers of children presenting for routine care, 41.7% would choose medical, or non-operative, therapy for their children with acute appendicitis. The risk of recurrence, time in hospital, and time out of school, pain, and knowing someone who has had appendicitis were all important factors that families may consider when making a decision. These data may be useful for surgeons counseling patients on which treatment to pursue., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Transcutaneous bilirubin measurements (TcBs) provide a noninvasive method for screening infants for hyperbilirubinemia and have been used extensively in term and late preterm newborns in well baby nurseries, offices, and outpatient clinics. Several studies have also demonstrated the utility of TcBs as a screening tool for infants > 28 weeks' gestation and their ability to reduce the need for blood sampling. The objectives of this study are to identify how often TcBs are used among California Newborn Intensive Care Units (NICUs) in preterm, late preterm and term infants, and other aspects of jaundice management., Methods: We conducted a survey on TcB use and practices relating to jaundice management in 150 California NICUs between April and October 2016., Results: TcB screening is routinely used in 28% (42/150) of NICUs. Only 7% (11/150) of NICUs use TcB in preterm infants < 28 weeks. Practice varied similarly across NICU levels of care. Among the subset of NICUs that responded to questions related to phototherapy and screening practices, prophylactic phototherapy was used in 38% (23/59) and 90% (55/61) screened for glucose-6-phosphate dehydrogenase deficiency based on race, ethnicity, and/or family history., Conclusion(s): Despite studies validating the accuracy of TcB in preterm infants > 28 weeks, only 28% of California NICUs routinely use TcB devices. TcB screening in infants < 28 weeks gestation is not widely used and no recommendation can be made in this regard until there is more experience with its application using a standardized protocol in these infants and on a large scale.

Objective: To evaluate the frequency, age at phototherapy (PT) initiation, and duration of PT use in infants 23 0/7 to 34 6/7 weeks of gestation in two neonatal intensive care units (NICUs) over 4 time periods., Study Design: We reviewed the charts of all infants born at 23 0/7 -34 6/7 weeks of gestational age (GA) and admitted to the NICUs of two hospitals between January 2009 and September 2015. We calculated the proportion of infants who received PT and the total duration of PT exposure., Results: Overall 2023 (81.8%) received PT, and PT use was inversely related to GA and birthweight. More infants received PT when GA was added as a criterion for initiating PT. The median duration (interquartile range (IQR)) of PT for all infants was 50 (27-85) h and in the lowest GA group was 74 (42-111) h., Conclusions: Recent US consensus guidelines appear to have led to an increased use of PT in our NICUs and studies from Norway indicate that we use PT considerably more frequently and for longer durations than do our Norwegian colleagues.

Aim: To identify neonates at risk of haemolytic hyperbilirubinaemia through near-concurrent measurements of total serum/plasma bilirubin (TB) or transcutaneous bilirubin (TcB) and end-tidal breath carbon monoxide (CO), corrected for ambient CO (ETCOc), an index of bilirubin production and haemolysis., Methods: Paired TB/TcB (mg/dL) and ETCOc (ppm) measurements were obtained in newborns (n = 283) at 20 to <60 hours of age in five nurseries. TB/TcB values were assigned TB/TcB percentile risk values using the Bhutani hour-specific nomogram. In infants having two serial TB/TcB measurements (n = 76), TB rate of rise (ROR, mg/dL/h) was calculated., Results: For the entire cohort (n = 283), 67.1% and 32.9% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.79 ± 1.84 vs 9.14 ± 2.25 mg/dL) and ETCOc (1.61 ± 0.45 vs 2.02 ± 1.35 ppm, p = 0.0002) were different between the groups. About 36.6% of infants with TB/TcB ≥75th percentile had ETCOc ≥ 2.0 ppm. In the subcohort of infants with serial TB/TcB measurements (n = 76), 44.7% and 55.3% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.28 ± 1.97 vs 9.53 ± 2.78 mg/dL), ETCOc (1.72 ± 0.48 vs 2.38 ± 1.89 ppm, p = 0.05) and TB ROR (0.011 ± 0.440 vs 0.172 ± 0.471 mg/dL/h) were different between the groups., Conclusion: The combined use of TB/TcB percentile risk assessments and ETCOc measurements can identify infants with haemolytic hyperbilirubinaemia. The addition of TB ROR can identify those infants with elimination disorders., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Extreme hyperbilirubinemia and kernicterus, though rare, continue to occur despite the adoption of universal screening. Unless they are known to have glucose-6-phosphate dehydrogenase deficiency, infants who currently develop kernicterus in high resource countries are often otherwise healthy newborns discharged from the well-baby nursery. In this review, we highlight risk factors that increase the risk of a newborn ≥35 weeks gestational age developing severe hyperbilirubinemia, as well as the risk factors that increase the hyperbilirubinemic infant's risk of kernicterus., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To document the intake of exclusively formula-fed newborns during the first 2 days of life., Methods: We enrolled a cohort of 50 healthy newborns ≥37 weeks' gestation and documented their daily formula intake until discharge. We surveyed pediatricians regarding their assessment of the intake of formula fed infants., Results: In all, 37 of 50 newborns stayed for at least 48 hours. The mean ± SD gestational age was 39.5 ± 0.88 weeks. Mean ±SD formula intake for the first 48 hours (n = 37) was 57.2 ± 20.4 mL/kg/d and mean weight loss at 45.7 ± 8.8 hours, was 2.7% of birth weight. Pediatricians underestimated the amounts taken by these infants., Conclusions: In the first 2 days, healthy term newborns, fed formula ad lib, consume about 115 mL/kg, about 2 to 3 times as much as breastfed infants, and they lose only 2.7% of their birthweight by 48 hours. Most pediatricians underestimate the intake of formula-fed infants.

Background: Even relatively low serum bilirubin concentrations can cause neurodevelopmental impairment in extremely low birth weight (EBWL) infants, while sequelae from hyperbilirubinemia in late preterm and term infants are rare and occur only at very high serum bilirubin levels. Phototherapy is the current treatment of choice., Objective: To present an update on the most important issues involved in phototherapy for jaundiced infants., Results: Light absorption by bilirubin in the skin transforms the native Z,Z-bilirubin to conformational photoisomers Z,E-bilirubin and E,Z-bilirubin and structural photoisomers E,Z-lumirubin and E,E-lumirubin. Formation and excretion of Z,E-bilirubin and E,Z-lumirubin are both important routes of elimination of bilirubin through bile and urine, although the precise contributions of the various photoisomers to the overall elimination of bilirubin are unknown. It appears that the photoisomers of bilirubin are predominantly formed in the plasma, and the rate of formation is affected by the hemoglobin concentration. Phototherapy lights with an emission spectrum of 460-490 nm provide the most efficient bilirubin-reducing light. LEDs should replace fluorescent tubes and halogen spotlights as the preferred light sources. Recent data raise concerns that sick ELBW infants under prolonged phototherapy may have an increased risk of death, though survivors may benefit from reduced rates of neurodevelopmental impairment. Comparison of the efficacy of cycled vs. continuous phototherapy has given divergent results. Changing the infant's position does not increase the efficacy of phototherapy., Conclusion: During the last decade, we have made progress in our understanding of how and where phototherapy works and in its practical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: To assess the efficacy of the heme oxygenase inhibitor, tin mesoporphyrin (SnMP), to reduce total bilirubin (TB) levels., Study Design: Masked, SnMP (4.5 mg kg(-1)), placebo-controlled, multicenter trial of single intramuscular injection to newborns ⩾35 weeks gestational age whose predischarge screening transcutaneous bilirubin (TcB) was >75th percentile., Results: Two hundred and thirteen newborns (median age 30 h) were randomized to treatment with SnMP (n=87) or 'sham' (n=89). We found that the duration of phototherapy was halved. Within 12 h of SnMP administration, the natural TB trajectory was reversed. At age 3 to 5 days, TB in the SnMP-treated group was +8% but sixfold lower than the 47% increase in the sham-treated group (P<0.001). At age 7 to 10 days, mean TB declined 18% (P<0.001) compared with a 7.1% increase among controls. No short-term adverse events from SnMP treatment were noted other than photoreactivity due to inadvertent exposure to white light phototherapy., Conclusion: Early, predischarge SnMP administration decreased the duration of phototherapy, reversed TB trajectory and reduced the severity of subsequent hyperbilirubinemia.

In pediatric office practices, we compared transcutaneous bilirubin levels in 689 newborns, age 3-10 days, with and without conjunctival icterus. In this age range, and in the absence of other clinical or laboratory indications, the presence of conjunctival icterus does not imply the need to measure the transcutaneous bilirubin or serum bilirubin level, but the absence of conjunctival icterus helps to rule out significant hyperbilirubinemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: In infants <35 weeks' gestation, we sought to define the transcutaneous bilirubin (TcB) levels at which a total serum bilirubin (TSB) level suggesting the need for phototherapy is unlikely to occur and a TSB measurement can, therefore, be avoided., Study Design: Nursing staff performed 896 TcB measurements within 1 h of a TSB on 225 neonates 26 0/7-34 6/7 weeks' postmenstrual age (PMA). Generalized linear models were fit with generalized estimating equations (GEEs) to model the probability of having a TSB level at or above the phototherapy initiation cutpoint as a function of the TcB; these methods allow for multiple tests per infant., Results: The mean difference between TcB and TSB measurements was <1 mg dl(-1) for each PMA category. When the TcB was at least 3 mg dl(-1) below the TSB cutpoint for phototherapy, there was a ⩾98% probability that the TSB was not at, or above, the recommended phototherapy level. The single exception to this was a phototherapy level of 6 mg dl(-1) for infants of 28 0/7-29 6/7 weeks' PMA, where a TcB of 4 mg dl(-1) below the phototherapy level (ie a TcB ⩽2 mg dl(-1)) was necessary to achieve ⩾98% probability., Conclusion: Our data support the use of routine TcB screening for infants 28-34 6/7 weeks' gestation. TcB screening in the neonatal intensive care unit can identify infants who require a TSB to confirm or exclude the need for phototherapy.