Better assessment of neonatal jaundice at home (BEAT Jaundice @home): protocol for a prospective, multicentre diagnostic study.

INTRODUCTION: Severe neonatal hyperbilirubinaemia can place a neonate at risk for acute bilirubin encephalopathy and kernicterus spectrum disorder. Early diagnosis is essential to prevent these deleterious sequelae. Currently, screening by visual inspection followed by laboratory-based bilirubin (LBB) quantification is used to identify hyperbilirubinaemia in neonates cared for at home in the Netherlands. However, the reliability of visual inspection is limited. We aim to evaluate the effectiveness of universal transcutaneous bilirubin (TcB) screening as compared with visual inspection to: (1) increase the detection of hyperbilirubinaemia necessitating treatment, and (2) reduce the need for heel pricks to quantify bilirubin levels. In parallel, we will evaluate a smartphone app (Picterus), and a point-of-care device for quantifying total bilirubin (Bilistick) as compared with LBB. METHODS AND ANALYSIS: We will undertake a multicentre prospective cohort study in nine midwifery practices across the Netherlands. Neonates born at a gestational age of 35 weeks or more are eligible if they: (1) are at home at any time between days 2 and 8 of life; (2) have their first midwife visit prior to postnatal day 6 and (3) did not previously receive phototherapy. TcB and the Picterus app will be used after visual inspection. When LBB is deemed necessary based on visual inspection and/or TcB reading, Bilistick will be used in parallel. The coprimary endpoints of the study are: (1) hyperbilirubinaemia necessitating treatment; (2) the number of heel pricks performed to quantify LBB. We aim to include 2310 neonates in a 2-year period. Using a decision tree model, a cost-effectiveness analysis will be performed. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethical Committee of the Erasmus MC Rotterdam, Netherlands (MEC-2020-0618). Parents will provide written informed consent. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NL9545).

Evaluation of a mobile application tool (BiliNorm) to improve care for newborns with hyperbilirubinemia in Indonesia.

BACKGROUND: Severe hyperbilirubinemia is more frequent in low- and middle-income countries such as Indonesia than in high-income countries. One of the contributing factors might be the lack of adherence to existing guidelines on the diagnosis and treatment of hyperbilirubinemia. We developed a new national guideline for hyperbilirubinemia management in Indonesia. To help healthcare workers use this guideline, a web-based decision support tool application may improve both the adherence to the guideline and the care for infants with hyperbilirubinemia. METHODS: We developed a web-based application (BiliNorm) to be used on a smartphone that displays the bilirubin level of the patient on the nomogram and advises about the treatment that should be started. Healthcare workers of two teaching hospitals in East Java, Indonesia, were trained on the use of BiliNorm. At 6 months after the introduction, a questionnaire was sent to those who worked with the application enquiring about their experiences. An observational study was conducted in two time epochs. A chart review of infants with hyperbilirubinemia in the two hospitals was sent. The appropriateness of hyperbilirubinemia management during a 6-month period before BiliNorm introduction was compared to that during a 7-month period after its introduction. RESULTS: A total of 43 participants filled in the questionnaire, the majority (72%) of them indicated that BiliNorm was well received and easy to use. Moreover, 84% indicated that BiliNorm was helpful for the decision to start phototherapy. Chart review of 255 infants before BiliNorm introduction and that of 181 infants after its introduction indicated that significantly more infants had received treatment according to the guideline (38% vs 51%, p = 0.006). Few infants received phototherapy, but bilirubin level was not measured (14% vs 7%, p = 0.024). There was no difference in the proportion of infants who were over- and under-treated (34% vs 32% and 14% vs 10%, respectively). CONCLUSIONS: The web-based decision tool BiliNorm appears to be a valuable application. It is easy to use for healthcare workers and helps them adhere to the guideline. It improves the care for infants with hyperbilirubinemia and may help reduce the incidence of severe hyperbilirubinemia in Indonesia.

Severe neonatal hyperbilirubinaemia: lessons learnt from a national perinatal audit.

OBJECTIVES: To describe characteristics of neonates with severe neonatal hyperbilirubinaemia (SNH) and to gain more insight in improvable factors that may have contributed to the development of SNH. DESIGN AND SETTING: Descriptive study, based on national Dutch perinatal audit data on SNH from 2017 to 2019. PATIENTS: Neonates, born ≥35 weeks of gestation and without antenatally known severe blood group incompatibility, who developed hyperbilirubinaemia above the exchange transfusion threshold. MAIN OUTCOME MEASURES: Characteristics of neonates having SNH and corresponding improvable factors. RESULTS: During the 3-year period, 109 neonates met the eligibility criteria. ABO antagonism was the most frequent cause (43%). All neonates received intensive phototherapy and 30 neonates (28%) received an exchange transfusion. Improvable factors were mainly related to lack of knowledge, poor adherence to the national hyperbilirubinaemia guideline, and to incomplete documentation and insufficient communication of the a priori hyperbilirubinaemia risk assessment among healthcare providers. A priori risk assessment, a key recommendation in the national hyperbilirubinaemia guideline, was documented in only six neonates (6%). CONCLUSIONS: SNH remains a serious threat to neonatal health in the Netherlands. ABO antagonism frequently underlies SNH. Lack of compliance to the national guideline including insufficient a priori hyperbilirubinaemia risk assessment, and communication among healthcare providers are important improvable factors. Implementation of universal bilirubin screening and better documentation of the risk of hyperbilirubinaemia may enhance early recognition of potentially dangerous neonatal jaundice.

Irradiance footprint of phototherapy devices: a comparative study.

BACKGROUND: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e., the illuminated area by the PT device with sufficient spectral irradiance, is essential for PT to be effective. Irradiance footprint measurements are not performed in current clinical practice. We describe a user-friendly method to systematically evaluate the high spectral irradiance (HSI) footprint (illuminated area with spectral irradiance of ≥30 µW cm-2 nm-1) of PT devices in clinical practice. MATERIALS AND METHODS: Six commercially available LED-based overhead PT devices were evaluated in overhead configuration with an incubator. Spectral irradiance (µW cm-2 nm-1) and HSI footprint were measured with a radiospectrometer (BiliBlanket Meter II). RESULTS: The average measured spectral irradiance ranged between 27 and 52 µW cm-2 nm-1 and HSI footprint ranged between 67 and 1465 cm2, respectively. Three, two, and one PT devices out of six covered the average BSA of an infant born at 22, 26-32, and 40 weeks of gestation, respectively. CONCLUSION: Spectral irradiance of LED-based overhead PT devices is often lower than manufacturer's specifications, and HSI footprints not always cover the average BSA of a newborn infant. The proposed measurement method will contribute to awareness of the importance of irradiance level as well as footprint measurements in the management of neonatal jaundice. IMPACT: While a sufficient spectral irradiance footprint is essential for PT to be effective, some PT devices have spectral irradiance footprints that are too small to cover the entire body surface area (BSA) of a newborn infant. This study introduces a user-friendly, accessible method to systematically evaluate the spectral irradiance level and footprint of PT devices. This study supports awareness on the role of the spectral irradiance footprint in the efficacy of PT devices. Irradiance footprint can be easily measured during phototherapy with the proposed method.

The knowledge of Indonesian pediatric residents on hyperbilirubinemia management.

Hyperbilirubinemia in the newborn occurs more frequently in Indonesia. Therefore, it is important that pediatric residents in Indonesia acquire adequate knowledge of hyperbilirubinemia management. This study aims to determine the pediatric residents' knowledge on hyperbilirubinemia management, whether they follow recommended guidelines, and whether differences exist between five large Indonesian teaching hospitals. We handed out a 25-question questionnaire on hyperbilirubinemia management to pediatric residents at five teaching hospitals. A total of 250 questionnaires were filled in completely, ranging from 14 to 113 respondents per hospital. Approximately 76% of the respondents used the Kramer score to recognize neonatal jaundice. Twenty-four percent correctly plotted the total serum bilirubin levels (TSB) on the phototherapy (PT) nomograms provided by the American Academy of Pediatrics (AAP) and the National Institute for Health and Care Excellence (NICE) for full-term and nearly full-term infants. Regarding preterm infants <35 weeks' gestational age, 66% of the respondents plotted TSB levels on the AAP nomogram, although this nomogram doesn't apply to this category of infants. Seventy percent of residents knew when to perform an exchange transfusion whereas 27% used a fixed bilirubin cut-off value of 20 mg/dL. Besides PT, 25% reported using additional pharmaceutical treatments, included albumin, phenobarbitone, ursodeoxycholic acid and immunoglobulins, while 47% of the respondents used sunlight therapy, as alternative treatment. The limited knowledge of the pediatric residents could be one factor for the higher incidence of severe hyperbilirubinemia and its sequelae. The limited knowledge of the residents raises doubts about the knowledge of the supervisors and the training of the residents since pediatric residents receive training from their supervisors.

Blue LED phototherapy in preterm infants: effects on an oxidative marker of DNA damage.

BACKGROUND: Phototherapy is used on the majority of preterm infants with unconjugated hyperbilirubinaemia. The use of fluorescent tube phototherapy is known to induce oxidative DNA damage in infants and has largely been replaced by blue light-emitting diode phototherapy (BLP). To date, it is unknown whether BLP also induces oxidative DNA damage in preterm infants. OBJECTIVE: To determine whether BLP in preterm infants induces oxidative DNA damage as indicated by 8-hydroxy-2'deoxyguanosine (8-OHdG). DESIGN: Observational cohort study. METHODS: Urine samples (n=481) were collected in a cohort of 40 preterm infants (24-32 weeks' gestational age) during the first week after birth. Urine was analysed for the oxidative marker of DNA damage 8-OHdG and for creatinine, and the 8-OHdG/creatinine ratio was calculated. Durations of phototherapy and levels of irradiance were monitored as well as total serum bilirubin concentrations. RESULTS: BLP did not alter urinary 8-OHdG/creatinine ratios (B=0.2, 95% CI -6.2 to 6.6) at either low (10-30 µW/cm2/nm) or high (>30 µW/cm2/nm) irradiance: (B=2.3, 95% CI -5.7 to 10.2 and B=-3.0, 95% CI -11.7 to 5.6, respectively). Also, the 8-OHdG/creatinine ratios were independent on phototherapy duration (B=-0.1, 95% CI -0.3 to 0.1). CONCLUSIONS: BLP at irradiances up to 35 µW/cm2/nm given to preterm infants ≤32 weeks' gestation does not affect 8-OHdG, an oxidative marker of DNA damage.

Current phototherapy practice on Java, Indonesia.

BACKGROUND: In Indonesia, the burden of severe hyperbilirubinemia is higher compared to other countries. Whether this is related to ineffective phototherapy (PT) is unknown. The aim of this study is to investigate the performance of phototherapy devices in hospitals on Java, Indonesia. METHODS: In 17 hospitals we measured 77 combinations of 20 different phototherapy devices, with and without curtains drawn around the incubator/crib. With a model to mimic the silhouette of an infant, we measured the irradiance levels with an Ohmeda BiliBlanket Meter II, recorded the distance between device and model, and compared these to manufacturers' specifications. RESULTS: In nine hospitals the irradiance levels were less than required for standard PT: < 10 µW/cm2/nm and in eight hospitals irradiance failed to reach the levels for intensive phototherapy: 30 µW/cm2/nm. Three hospitals provided very high irradiance levels: > 50 µW/cm2/nm. Half of the distances between device and model were greater than recommended. Distance was inversely correlated with irradiance levels (R2 = 0.1838; P < 0.05). The effect of curtains on irradiance levels was highly variable, ranging from - 6.15 to + 15.4 µW/cm2/nm, with a mean difference (SD) of 1.82 (3.81) µW/cm2/nm (P = 0.486). CONCLUSIONS: In half of the hospitals that we studied on Java the levels of irradiance are too low and, in some cases, too high. Given the risks of insufficient phototherapy or adverse effects, we recommend that manufacturers provide radiometers so hospitals can optimize the performance of their phototherapy devices.

Should transcutaneous bilirubin be measured in preterm infants receiving phototherapy? The relationship between transcutaneous and total serum bilirubin in preterm infants with and without phototherapy.

Our objective was to analyze the relationship between transcutaneous bilirubin (TcB) measured on an unexposed area of skin and total serum bilirubin (TSB) in preterm infants before, during, and after phototherapy (PT). For this purpose paired TSB and TcB levels were measured daily during the first ten days after birth in preterm infants of less than 32 weeks' gestation. TcB was measured with a Dräger Jaundice Meter JM-103 on the covered hipbone. Agreement between TSB and TcB levels was assessed before, during, and after PT. True negative and corresponding false negative percentages were calculated using different TcB cut-off levels. Data are presented as mean (±SD). We obtained 856 paired TcB and TSB levels in 109 preterm infants (66 boys, gestational age 29.4 ± 1.6 weeks and birth weight 1282 g ± 316 g). We found that the difference between TSB and TcB before PT was significantly lower, 44 (±36) µmol/L, than the difference during and after PT, 61 (±29) µmol/L and 63 (±25) µmol/L, respectively; P < 0.01. Blood sampling could be reduced by 42%, with 2% false negatives, when 50 µmol/L was added to the TcB level at 70% of the PT threshold. Our conclusion is that phototherapy enhances underestimation of TSB by TcB in preterms, even if measured on unexposed skin. The use of specific TcB cut-off levels substantially reduces the need for TSB measurements.

LED-phototherapy does not induce oxidative DNA damage in hyperbilirubinemic Gunn rats.

BACKGROUND: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. Fluorescent tube (FT)-emitted PT light is known to induce oxidative DNA damage in neonates. Nowadays, however, FTs have largely been replaced by light-emitting diodes (LEDs) for delivering PT. Until now, it is unknown whether LED-PT causes oxidative DNA damage. We aim to determine whether LED-PT induces oxidative DNA damage in hyperbilirubinemic rats. METHODS: Adult Gunn rats, with genetically unconjugated hyperbilirubinemia, received LED-PT in the clinically relevant doses of 10 or 30 µW/cm2/nm. Urine was collected at 0, 24, and 48 h of PT. A group of young Gunn rats received intensive LED-PT of 100 µW/cm2/nm for 24 h. Urine was collected every 8 h and analyzed for the levels of oxidative DNA damage marker 8-hydroxy-2'deoxyguanosine (8-OHdG) and creatinine. DNA damage was evaluated by immunohistochemistry (γH2AX) of skin and spleen samples. RESULTS: LED-PT of 10 and 30 µW/cm2/nm did not affect urinary concentrations of 8-OHdG and creatinine or the 8-OHdG/creatinine ratio. Likewise, intensive LED-PT did not affect the 8-OHdG/creatinine ratio or the number of γH2AX-positive cells in the skin or spleen. CONCLUSIONS: Our results show that LED-PT does not induce oxidative DNA damage in hyperbilirubinemic Gunn rats either at clinically relevant or intensive dosages.

Adherence to hyperbilirubinemia guidelines by midwives, general practitioners, and pediatricians in Indonesia.

Severe hyperbilirubinemia, which may result in kernicterus, is seen more frequently in low and middle-income countries, such as Indonesia, than in high-income countries. In Indonesia midwives, general practitioners (GPs), and pediatricians are involved in the care of jaundiced newborn infants. It is unknown whether the high incidence of severe hyperbilirubinemia in this country is related to a lack of awareness of existing hyperbilirubinemia guidelines issued by, for example, the World Health Organization, the American Academy of Pediatrics, or the Indonesian Health Ministry, or to a lack of adherence to such guidelines. The aim of this questionnaire study was to assess health professionals' awareness of existing guidelines and their adherence to these guidelines in daily practice. We handed out a ten-question questionnaire to midwives, GPs, and pediatricians that included questions about the professionals themselves as well as clinical questions. The midwives completed 291 questionnaires, the GPs 206, and the pediatricians 154, all of which we used for our analysis. Almost 30% of the midwives and 23% of the GPs were either unaware of any existing guidelines or they did not adhere to them. Only 54% of the midwives recognized the warning signs of severe hyperbilirubinemia correctly, compared to 68% of the GPs and 89% of the pediatricians. Twenty-eight percent of the midwives and 31% of the GPs indicated that their first follow-up visit was after 72 hours, while 90% of them discharged infants after less than 48 hours after birth. The awareness of and adherence to guidelines for preventing and treating hyperbilirubinemia is low amongst the midwives and GPs in Indonesia. This may be an important contributing factor in the high incidence of severe hyperbilirubinemia in Indonesia.

Unconjugated free bilirubin in preterm infants.

BACKGROUND: Hyperbilirubinemia guidelines are based on total serum bilirubin (TSB), in combination with either gestational age (GA) or birth weight (BW), postnatal age and specific risk factors. However, TSB is a poor predictor of bilirubin-induced neurotoxicity (BIND). Free unconjugated bilirubin (UCBfree) and the UCBfree/TSB ratio are more directly related to BIND, but data on their postnatal courses are unknown. AIMS: To characterize the postnatal courses of UCBfree and UCBfree/TSB ratio, and assess their relationships with clinical characteristics. SUBJECTS: 72 preterm infants≤32weeks GA, admitted to the University Medical Center Groningen, The Netherlands. STUDY DESIGN: During the first postnatal week, bilirubin plasma parameters were analyzed and their relationship with clinical parameters was analyzed. Postnatal changes were analyzed using Generalized Estimating Equations. Data are expressed as medians [ranges]. RESULTS: Less than 10% of the cohort (GA: 29 [26-31] weeks; BW: 1165 [600-1975] g) showed hyperbilirubinemic risk factors. We observed a large variation in UCBfree (27 [1-197] nmol/L), that could partly be explained by postnatal age and gender, but not by other risk factors. Maximal UCBfree levels of 50 [13-197] nmol/L occurred at day 4 and were higher in males. In contrast to TSB, UCBfree/TSB ratios (0.19 [0.01-1.04]) were higher in infants with low GA/BW. CONCLUSION: UCBfree levels vary considerably in preterm infants, despite a low incidence of hyperbilirubinemic risk factors and similar TSB-based phototherapy treatment. UCBfree could not be predicted by GA or BW, but UCBfree/TSB ratios are highest in the smallest preterms, while they have the lowest TSB levels.

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

BACKGROUND AND OBJECTIVE: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. METHODS: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. RESULTS: Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g. CONCLUSIONS: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74465643.

Optimizing exchange transfusion for severe unconjugated hyperbilirubinemia: studies in the Gunn rat.

BACKGROUND: Severe unconjugated hyperbilirubinemia carries the risk of neurotoxicity. Phototherapy (PT) and exchange transfusion (ET) are cornerstones in the treatment of unconjugated hyperbilirubinemia. Studies to improve ET efficacy have been hampered by the low application of ET in humans and by the lack of an in vivo model. The absence of an appropriate animal model has also prevented to determine the efficacy of adjunct or alternative treatment options such as albumin (Alb) administration. AIM: To establish an in vivo model for ET and to determine the most effective treatment (combination) of ET, PT and Alb administration. METHODS: Gunn rats received either PT, PT+Alb, ET, ET+PT, ET+PT+Alb or sham operation (each n = 7). ET was performed via the right jugular vein in ≈ 20 min. PT (18 µW/cm(2)/nm) was started after ET or at T0. Albumin i.p. injections (2.5 g/kg) were given after ET or before starting PT. Plasma unconjugated bilirubin (UCB), plasma free bilirubin (Bf), and brain bilirubin concentrations were determined. RESULTS: We performed ET in 21 Gunn rats with 100% survival. At T1, ET was profoundly more effective in decreasing both UCB -44%, p<0.01) and Bf -81%, p<0.05) than either PT or PT+Alb. After 48 h, the combination of ET+PT+Alb showed the strongest hypobilirubinemic effect (-54% compared to ET). CONCLUSIONS: We optimized ET for severe unconjugated hyperbilirubinemia in the Gunn rat model. Our data indicate that ET is the most effective treatment option, in the acute as well as the follow-up situation.

Beyond plasma bilirubin: the effects of phototherapy and albumin on brain bilirubin levels in Gunn rats.

BACKGROUND & AIMS: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCB(free)), the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCB(free) fraction, and thus decrease bilirubin accumulation in the brain. METHODS: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemic Gunn rats with phototherapy, human serum albumin (HSA) or phototherapy+HSA. RESULTS: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCB(free) and brain bilirubin by 88% and 67%, respectively (p<0.001). In the acute model, adjunct HSA also increased the efficacy of phototherapy; it decreased plasma UCB(free) by 76% (p<0.001) and completely prevented the hemolysis-induced deposition of bilirubin in the brain. Phototherapy alone failed to prevent the deposition of bilirubin in the brain during acute hemolytic jaundice. CONCLUSIONS: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCB(free) in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice.

High variability and low irradiance of phototherapy devices in Dutch NICUs.

OBJECTIVE: To evaluate phototherapy practices by measuring the irradiance levels of phototherapy (PT) devices. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care units. PATIENTS: None. INTERVENTIONS: Irradiance levels of PT devices used in the 10 Dutch Neonatal Intensive Care Units (NICUs) were measured according to the local PT practice patterns. The irradiance levels of all overhead and fibre-optic PT devices were measured with a radiometer using an infant silhouette model. RESULTS: Eight different PT devices were used in the 10 NICUs; five were overhead devices and three fibre-optic pads. The median (range) irradiance level for overhead PT devices was 9.7 (4.3-32.6) µW/cm(2)/nm and for fibre-optic pads 6.8 (0.8-15.6) µW/cm(2)/nm. Approximately 50% of PT devices failed to meet the minimal recommended irradiance level of 10 µW/cm(2)/nm. Maximal irradiance levels for overhead PT spot lights were inversely related to the distance between device and infant model (R2=0.33). The distances ranged from 37 cm to 65 cm. CONCLUSIONS: PT devices in the Dutch NICUs show considerable variability with often too low irradiance levels. These results indicate that suboptimal PT is frequently applied and may even be ineffective towards reducing total serum bilirubin levels. These results underline the need for greater awareness among all healthcare workers towards the requirements for effective PT including measurements of irradiance and distance.

Moderate unconjugated hyperbilirubinemia causes a transient but delayed suppression of amplitude-integrated electroencephalographic activity in preterm infants.

BACKGROUND: Unconjugated hyperbilirubinemia occurs frequently in preterm infants and may result in bilirubin encephalopathy. Amplitude-integrated electroencephalography (aEEG) is used to evaluate brain function in newborns. OBJECTIVES: To investigate the influence of total serum bilirubin (TSB) on the aEEG amplitude of preterm infants and to evaluate aEEG as a noninvasive method to identify acute bilirubin encephalopathy. METHODS: We performed a prospective observational study of 34 infants with a gestational age (GA) of 26-31 6/7 weeks. Infants had aEEG recordings on the 1st-5th, 8th and 15th day after birth. Infants with asphyxia, intraventricular hemorrhage >grade I or circulatory insufficiency were excluded. aEEG was evaluated by calculating the mean 5th, 50th and 95th centiles of the aEEG amplitudes. RESULTS: TSB peaked on the 4th day after birth. There was no synchronous relationship between TSB and aEEG amplitudes. The 5th, 50th, and 95th aEEG amplitude centiles on the 8th day correlated negatively with the TSB peak value (r = -0.37, p = 0.048; r = -0.60, p = 0.001; r = -0.44, p = 0.017, respectively), irrespective of GA. The 5th and 50th aEEG amplitude centiles increased with increasing GA (r = 0.45, p < 0.001, and r = 0.26, p < 0.001, respectively) and postnatal age (r = 0.25, p < 0.001, and r = 0.16, p = 0.023, respectively). CONCLUSIONS: TSB had no direct effect on aEEG amplitudes in preterm infants. There is, however, a delayed effect on electrocerebral activity in the 2nd week after birth.

Early corticosteroid treatment does not affect severity of unconjugated hyperbilirubinemia in extreme low birth weight preterm infants.

AIM: To determine the relationship between early postnatal dexamethasone (DXM) treatment and the severity of hyperbilirubinemia in extreme low birth weight (ELBW) preterm infants. METHODS: In 54 ELBW preterm infants, total serum bilirubin concentrations (TSB) and phototherapy (PT) data during the first 10 days were evaluated retrospectively. ELBW infants had participated in a randomized controlled trial of early DXM treatment which aimed to assess effects on chronic lung disease. Infants had been treated with DXM (0.25 mg/kg twice daily at postnatal day 1 and 2) or with placebo (normal saline). Analysis was performed on an intention to treat basis. RESULTS: Twenty-five Infants had been randomized into the DXM group; 29 into the placebo group. Mean (±SD) TSB [120 (±19) µmol/L vs. 123 (±28) µmol/L, DXM versus placebo, respectively] and maximum TSB [178 (±23) µmol/L vs. 176 (±48), DXM versus placebo, respectively] concentrations were similar. TSB concentrations peaked 30 h earlier in the DXM group (p ≤ 0.05). The need for PT as well as the duration of PT was similar in both groups. CONCLUSIONS: Early DXM treatment does not affect the severity of neonatal hyperbilirubinemia in ELBW preterm infants. Our results seem compatible with the concept that factors other than bilirubin conjugation capacity are important for the pathophysiology of neonatal jaundice in ELBW preterm infants.

[Uniform intervention criteria for jaundice in hyperbilirubinemia in preterm infants]. / Uniforme bilirubinegrenzen voor de behandeling van icterische premature neonaten.

OBJECTIVE: To compare the guidelines of the 10 Dutch neonatal intensive care units (NICUs) for the treatment of preterm infants with hyperbilirubinemia, in order to develop uniform threshold levels for the total serum concentration of bilirubin (TSB) above which treatment with phototherapy or exchange transfusion is indicated. DESIGN: Survey. METHODS: Guidelines for hyperbilirubinemia in preterm infants (gestational age < 32 weeks) from all 10 Dutch NICUs were obtained and compared with each other and with international guidelines. RESULTS: All 10 NICUs used intervention criteria based on TSB. 9 NICUs used TSB thresholds based on birth weight (1 used gestational age) with 2, 3 or 5 categories. 6 NICUs used age-specific TSB thresholds and 4 NICUs used a constant TSB threshold. The maximum range in TSB thresholds was 170 micromol/l for phototherapy and 125 micromol/l for exchange transfusion. Acidosis, sepsis, asphyxia, active haemolysis and intraventricular haemorrhage were the risk factors most frequently used. During a consensus meeting with representatives of the 10 NICUs, a guideline was agreed upon that will now be used for all neonates with a gestational age < 35 weeks. CONCLUSION: There was considerable variation in the TSB thresholds used to date by the 10 NICUs. Now in the Netherlands, in addition to guideline 'Hyperbilirubinemia' for children with a gestational age >or= 35 weeks, 'uniform yellow thresholds' shall be used for jaundiced preterm infants with a gestational age < 35 weeks.