Management of severe hyperbilirubinemia in the cholestatic neonate: a review and an approach.

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 (≥340/7-366/7 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.

Natural history of early neonatal bilirubinemia: a global perspective.

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.

Heme Catabolism and Bilirubin Production in Readmitted Jaundiced Newborns.

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.

Sixty years of phototherapy for neonatal jaundice - from serendipitous observation to standardized treatment and rescue for millions.

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.

Factors influencing choice of medical vs. surgical treatment of pediatric appendicitis.

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.

Transcutaneous bilirubinometer use and practices surrounding jaundice in 150 California newborn intensive care units.

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.

Frequency and duration of phototherapy in preterm infants <35 weeks gestation.

OBJECTIVE: To evaluate the frequency, age at phototherapy (PT) initiation, and duration of PT use in infants 230/7 to 346/7 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 230/7-346/7 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.

Identification of risk for neonatal haemolysis.

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.

Update on Phototherapy in Jaundiced Neonates.

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.