Clinical overview of phototherapy for neonatal hyperbilirubinaemia.

The most efficient emission spectrum of light for phototherapy is blue-green light emission diode light with peak emission at 478 nm. In the irradiance interval of phototherapy, the relationship between efficacy and irradiance is almost linear, and it is negatively related to the haemoglobin. The action sites of phototherapy are the extravascular compartment and cutaneous blood. The most immature neonates treated aggressively had not only a lower frequency of neurodevelopmental impairment than conservatively treated, but also greater mortality. Intermittent and continuous phototherapy are assumed to be equally efficient. Home-based fibreoptic phototherapy is effective and safe. Important progress is still occurring in phototherapy.

Action spectrum of phototherapy in hyperbilirubinemic neonates.

BACKGROUND: Phototherapy with blue light matching plasma absorption spectrum of the bilirubin-albumin complex with peak at 460 nm is standard treatment of neonatal hyperbilirubinemia. AIM: To demonstrate clinically the action (efficacy) spectrum of phototherapy in hyperbilirubinemic neonates, through determination of the fraction of total serum bilirubin (TSB) decreased by phototherapy with peak emission wavelengths ≥478 nm (blue-green) compared with that of light of 459/452 nm (blue). METHODS: TSB values were compiled from three earlier trials, in which hyperbilirubinemic neonates were randomized to receive 24 h of either blue-green light (478/490/497 nm) (intervention groups) or blue light (459/452/459 nm) (control groups) with equal irradiance and exposed body surface areas. Ratios (efficacy) between the decrease in TSB between intervention and control groups were calculated and graphed versus peak wavelengths, demonstrating the course of the action spectrum. RESULTS: Calculated efficacy ratios were 1.31, 1.18, and 1.04 for light with peak wavelengths of 478, 490, and 497 nm, respectively. The action spectrum increases from 452/459 to maximum at 478 nm, from where it decreases to 1.18 and finally to 1.04. CONCLUSION: For optimal phototherapeutic treatment, neonates need to be exposed to light with peak wavelength some 20 nm longer than is presently used. IMPACT: The action (efficacy) spectrum of phototherapy for hyperbilirubinemic neonates has its peak wavelength at 478 nm. The peak wavelength of this action spectrum is 20 nm longer than the wavelength presently believed to be most efficient. The peak is also different from the peak found in vitro. For optimal phototherapeutic effect, neonates need to be treated with light of wavelengths some 20 nm longer than are presently used.

Blue-Green (~480 nm) versus Blue (~460 nm) Light for Newborn Phototherapy-Safety Considerations.

We have previously shown that the phototherapy of hyperbilirubinemic neonates using blue-green LED light with a peak wavelength of ~478 nm is 31% more efficient for removing unconjugated bilirubin from circulation than blue LED light with a peak wavelength of ~452 nm. Based on these results, we recommended that the phototherapy of hyperbilirubinemic newborns be practiced with light of ~480 nm. Aim: Identify and discuss the most prominent potential changes that have been observed in the health effects of phototherapy using either blue fluorescent- or blue LED light and speculate on the expected effects of changing to blue-green LED light phototherapy. Search the phototherapy literature using the terms neonate, hyperbilirubinemia, and phototherapy in the PubMed and Embase databases. Transitioning from blue fluorescent light to blue-green LED light will expose neonates to less light in the 400-450 nm spectral range, potentially leading to less photo-oxidation and geno-/cytotoxicity, reduced risk of cancer, and decreased mortality in extremely low-birthweight neonates. The riboflavin level may decline, and the increased production and retention of bronze pigments may occur in predisposed neonates due to enhanced lumirubin formation. The production of pre-inflammatory cytokines may rise. Hemodynamic responses and transepidermal water loss are less likely to occur. The risk of hyperthermia may decrease with the use of blue-green LED light and the risk of hypothermia may increase. Parent-neonate attachment and breastfeeding will be positively affected because of the shortened duration of phototherapy. The latter may also lead to a significant reduction in the cost of phototherapy procedures as well as the hospitalization process.

Effect of blue LED phototherapy centered at 478 nm versus 459 nm in hyperbilirubinemic neonates: a randomized study.

BACKGROUND: Treatment of choice for hyperbilirubinemic neonates is blue light matching the absorption spectrum of bilirubin-albumin in vitro with maximum absorption at 459 nm. Blue LED light centered at 478 nm was hypothesized as being more efficient than that centered at 459 nm. This study compares the bilirubin-reducing effect of the two light qualities with equal irradiance in a randomized nonblinded clinical trial. METHODS: Inclusion criteria were healthy hyperbilirubinemic neonates with gestational age ≥33 weeks. Forty-nine neonates included in each group received phototherapy from above for 24 h. Mean irradiances were 9.2 × 1015 and 9.0 × 1015 photons/cm2/s for the 478 and 459 nm groups, respectively. RESULTS: Mean [95% CI] decreases in total serum bilirubin were 150 [141, 158] and 120 [111, 130] µmol/L for the 478 and 459 nm groups, respectively; mean difference was 29 [17, 42] µmol/L. Mean [95% CI] percentage decreases in bilirubin were 54.8% [52.5, 57.0] and 41.8% [39.3, 44.3]; mean difference was 12.9 [9.6, 16.3] percentage points. After adjustment this difference was 13.4 [10.2, 16.7] percentage points. All differences were highly statistically significant (P < 0.001). CONCLUSION: Blue LED light centered at 478 nm had a greater bilirubin-reducing effect than that centered at 459 nm with equal irradiance quantified as photon fluence rate. IMPACT: Blue LED light centered at 478 nm had a greater in vivo bilirubin-reducing effect than blue LED light centered at 459 nm with equal irradiance quantified as photon fluence rate in the treatment of hyperbilirubinemic late preterm or term neonates. LED light centered at 478 nm might reduce the duration of phototherapy compared to LED light centered at 459 nm as the same effect can be obtained while exposing the infants to fewer photons. Blue light matching the absorption spectrum of the bilirubin-albumin complex in vitro with peak absorption at 459 nm is used worldwide as it is considered to be the most effective light for phototherapy of jaundiced neonates. This study showed that blue LED light centered at 478 nm had a greater bilirubin-reducing effect than blue LED light centered at 459 nm. Therefore, blue LED light centered at 478 nm should be used instead of blue light centered at 459 nm. By this, the risk of potential side effects might be minimized, and the duration of phototherapy potentially reduced.

Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer.

BACKGROUND: Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns. METHODS: We conducted a case-control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy. RESULTS: We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns. CONCLUSIONS: There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment. IMPACT: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn. Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia. Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B. Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

A greater awareness of children with glucose-6-phosphate dehydrogenase deficiency is imperative in western countries.

AIM: This national retrospective Danish study described the characteristics of children diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited X-linked recessive disorder that often affects children of Middle Eastern descent. METHODS: We studied children born between 1 January 2000 and 31 December 2017 and diagnosed with G6PD deficiency. They were identified from the Danish National Hospital Discharge Register and the Danish Database of Extreme Neonatal Hyperbilirubinaemia. RESULTS: There were 113 children diagnosed with G6PD deficiency, 67% were of Middle Eastern descent and they were frequently diagnosed before the onset of symptoms, based on known heredity. Of the 67 infants born in Denmark, 10% had extreme neonatal hyperbilirubinaemia and one developed kernicterus spectrum disorder, as did one child born in the Middle East. Most (61%) of the 33 children with jaundice received phototherapy, 12% had exchange transfusions and 18% received whole blood transfusions. After the neonatal period, 23% of the cohort had blood transfusions and 4% needed intensive care for acute haemolytic anaemia. The incidence of G6PD deficiency appeared to be severely underestimated. CONCLUSION: Many families from countries where G6PD deficiency is endemic move to Denmark and other Western countries. Greater awareness is essential to avoid chronic and potentially lethal, consequences.

Predicting respiratory distress syndrome at birth using fast test based on spectroscopy of gastric aspirates. 1. Biochemical part.

AIM: To develop a fast bedside lung maturity test. METHODS: Gastric aspirates obtained from premature infants contain lamellar bodies, carrying lung surfactant. To estimate lung maturity, we isolated lamellar bodies from fresh gastric aspirates by centrifugation. Erythrocytes and other cells were lysed by adding water and discarded subsequently with the supernatant. Mid-infrared spectroscopy was then performed to measure the lung maturity as lecithin-sphingomyelin ratio. Lecithin was determined as dipalmitoylphosphatidylcholine, the most surface-active phospholipid. Algorithms to measure lecithin and sphingomyelin concentrations in fresh gastric aspirates were developed on aspirates from 140 premature infants. Each gastric aspirate sample was divided into two samples: one for mass spectrometry as reference and one for spectroscopy. Development of the algorithm is described in detail in Appendix S1. RESULTS: Gastric aspirates stored at 4-5°C avoid flocculation of proteins and phospholipids in contrast to when the aspirates were frozen and thawed. Omission of freezing and concentration of the lung surfactant by centrifugation combined with diminished influence of proteins improves the spectroscopic measurement of lecithin-sphingomyelin ratio. Measurement of lecithin-sphingomyelin ratio by the new method was performed within 10-15 minutes. CONCLUSION: We present a new fast bedside lung maturity test on fresh gastric aspirate for early targeted surfactant treatment.

Predicting respiratory distress syndrome at birth using a fast test based on spectroscopy of gastric aspirates: 2. Clinical part.

AIM: To evaluate the accuracy of our new rapid point-of-care (POC) test for lung maturity. The method as we describe in an accompanying article was developed with the purpose of improving the outcome from respiratory distress syndrome (RDS). The test enables the delivery of surfactant in infants with immature lungs already at birth and ensures that infants with mature lungs are not treated unnecessarily. METHODS: Fresh gastric aspirate (GAS) was sampled at birth in a cohort of preterm infants with gestational ages ranging between 24 and 31 completed weeks for lung surfactant measurement as lecithin-sphingomyelin ratio (L/S). L/S was prospectively compared with RDS development. The clinical outcome was blinded for the investigators of L/S. The time for analysis was <15 minutes. RESULTS: GAS was obtained from 72 infants. Forty-four (61%) developed RDS. The cut-off for L/S was 3.05; predicting RDS with a sensitivity of 91% and specificity of 79%. CONCLUSION: The new improved spectroscopic L/S method of lung maturity on GAS has high sensitivity. The method is designed for use as a POC test at birth, and a spectroscopic prototype has been developed for bedside use. Clinical trials with this new lung maturity test are planned.

Extreme neonatal hyperbilirubinemia, acute bilirubin encephalopathy, and kernicterus spectrum disorder in children with galactosemia.

BACKGROUND: Galactosemia has not been recognized as a cause of extreme neonatal hyperbilirubinemia, although growing evidence supports this association. METHODS: In a retrospective cohort study, we identified children with galactosemia due to GALT deficiency using the Danish Metabolic Laboratory Database. Among these, we identified children with extreme neonatal hyperbilirubinemia or symptoms of ABE. Extreme neonatal hyperbilirubinemia was defined as maximum total serum bilirubin (TSBmax)) level ≥450 µmol/L and a ratio of conjugated serum bilirubin/TSB <0.30. RESULTS: We identified 21 children with galactosemia (incidence:1:48,000). Seven children developed extreme neonatal hyperbilirubinemia (median [range] TSBmax level: 491 [456-756] µmol/L), accounting for 1.7% of all extreme neonatal hyperbilirubinemia cases. During the first 10 days of life, hyperbilirubinemia was predominantly of unconjugated type. Four children developed symptoms of intermediate/advanced ABE. One additional child had symptoms of intermediate/advanced ABE without having extreme neonatal hyperbilirubinemia. On follow-up, one child had KSD. CONCLUSIONS: Galactosemia is a potential cause of extreme neonatal hyperbilirubinemia, ABE, and KSD. It is crucial that putative galactosemic children are treated aggressively with phototherapy to prevent ABE and KSD. Thus it is important that galactosemia is part of the work up for unconjugated hyperbilirubinemia.

The impact of hemoglobin on the efficacy of phototherapy in hyperbilirubinemic infants.

BackgroundPhototherapy is the routine treatment for neonatal hyperbilirubinemia. Absorption of light in the skin transforms the native Z,Z-bilirubin to photobilirubins. This study investigates whether the hemoglobin concentration has an impact on efficacy of phototherapy, expressed by the decline of total serum bilirubin concentration (TsB).MethodsA trial was conducted on 93 infants, gestational age ≥33 weeks, with uncomplicated hyperbilirubinemia. The infants were treated with conventional phototherapy using LED light for 24 h. The median light irradiance was 66.8 µW/cm2/nm.ResultsThe median decrease in TsB after 24 h was 121 (57-199) µmol/l; the median hemoglobin was 12.0 (7.0-14.7) mmol/l. There was a significant effect of hemoglobin concentration on the decrease in TsB of -3.61 µmol/mmol hemoglobin (P=0.022), after adjusting for initial TsB and postnatal age. That is, assuming the same initial TsB and postnatal age, for each mmol/l increase in hemoglobin, the decrease in TsB was 3.61 µmol/l smaller. In our hemoglobin range, the decrease in TsB is reduced by 28 µmol/l (23%).ConclusionIncreasing hemoglobin levels led to a decrease in the efficacy of phototherapy. Our data provide additional support for the conclusion that the transformation of bilirubin to photobilirubins takes place mainly in the superficial capillaries of the skin.

Rapid test for lung maturity, based on spectroscopy of gastric aspirate, predicted respiratory distress syndrome with high sensitivity.

AIM: Respiratory distress syndrome (RDS) is a major cause of mortality and morbidity in premature infants. By the time symptoms appear, it may already be too late to prevent a severe course, with bronchopulmonary dysplasia or mortality. We aimed to develop a rapid test of lung maturity for targeting surfactant supplementation. METHODS: Concentrations of the most surface-active lung phospholipid dipalmitoylphosphatidylcholine and sphingomyelin in gastric aspirates from premature infants were measured by mass spectrometry and expressed as the lecithin/sphingomyelin ratio (L/S). The same aspirates were analysed with mid-infrared spectroscopy. Subsequently, L/S was measured in gastric aspirates and oropharyngeal secretions from another group of premature infants using spectroscopy and the results were compared with RDS development. The 10-minute analysis required 10 µL of aspirate. RESULTS: An L/S algorithm was developed based on 89 aspirates. Subsequently, gastric aspirates were sampled in 136 infants of 24-31 weeks of gestation and 61 (45%) developed RDS. The cut-off value of L/S was 2.2, sensitivity was 92%, and specificity was 73%. In 59 cases, the oropharyngeal secretions had less valid L/S than gastric aspirate results. CONCLUSION: Our rapid test for lung maturity, based on spectroscopy of gastric aspirate, predicted RDS with high sensitivity.

Effect of phototherapy with turquoise vs. blue LED light of equal irradiance in jaundiced neonates.

BACKGROUND: Blue light with peak emission around 460 nm is the preferred treatment of neonatal hyperbilirubinemia. However, studies using fluorescent light tubes have suggested that turquoise light with peak emission at 490 nm may be more efficient. At present, the predominant light source for phototherapy is light emitting diodes (LEDs). Hence, the aim of this study was to compare the bilirubin-reducing effect in jaundiced neonates treated either with turquoise or with blue LED light with peak emission at 497 or 459 nm, respectively, with equal irradiance on the infants. METHODS: Infants with gestational age ≥33 wk and uncomplicated hyperbilirubinemia were randomized to either turquoise or blue LED light and were treated for 24 h. The mean irradiance footprint at skin level was 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively. RESULTS: Forty-six infants received turquoise light and 45 received blue light. The median (95% confidence interval) decrease of total serum bilirubin was 35.3% (32.5; 37.3) and 33.1% (27.1; 36.8) for infants treated with turquoise and blue lights, respectively. The difference was nonsignificant (P = 0.53). The decrease was positively correlated to postnatal age and negatively to birth weight. CONCLUSION: Using LED light of equal irradiance, turquoise and blue lights had equal bilirubin-reducing effect on hyperbilirubinemia of neonates.

Bilirubin isomer distribution in jaundiced neonates during phototherapy with LED light centered at 497 nm (turquoise) vs. 459 nm (blue).

BACKGROUND: Phototherapy using blue light is the treatment of choice worldwide for neonatal hyperbilirubinemia. However, treatment with turquoise light may be a desirable alternative. Therefore, the aim of this randomized, controlled study was to compare the bilirubin isomer distribution in serum of jaundiced neonates after 24 h of therapy with narrow-band (LED) light centered at 497 nm (turquoise) vs. 459 nm (blue), of essentially equal irradiance. MATERIALS: Eighty-three neonates (≥33 wk gestational age) with uncomplicated hyperbilirubinemia were included in the study. Forty neonates were exposed to light centered at 497 nm and 43 infants with light centered at 459 nm. Irradiances were 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively. RESULTS: After 24 h of treatment no significant differences in serum concentrations of total bilirubin isomers and Z,Z-bilirubin were observed between the 2 groups. Interestingly, concentrations of Z,E-bilirubin, and thus also total bilirubin isomers formed during therapy, were highest for infants receiving light centered at 459 nm, while the concentration of E,Z-bilirubin was highest for those receiving light centered at 497 nm. No significant difference was found between concentrations of E,Z-lumirubin. CONCLUSION: Therapy with LED light centered at 497 nm vs. 459 nm, applied with equal irradiance on the infants, resulted in a different distribution of bilirubin isomers in serum.

Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes.

BACKGROUND: In neonatal jaundice, phototherapy converts bilirubin to more polar photoisomers which can be excreted without conjugation. We measured changes in the concentration of bilirubin Z,E-photoisomer during the first 4 h of intensive phototherapy using single fluorescent lights as a reference, compared to double fluorescent lights, and a single unit of photodiodes. METHODS: Neonates (N = 42; birth weight: 1,200-4,690 g; gestational age: 28-42 wk) were studied during phototherapy. Infants were randomized to: (i) single, or (ii) double fluorescent phototherapy; or (iii) single unit photodiodes. Irradiance was measured. Serum bilirubin (by cooximetry) and Z,E bilirubin (by high-pressure liquid chromatography) were measured at 0,15, 30, 60, 120, and 240 min after the start of phototherapy. Data were analyzed with a linear mixed model. RESULTS: There was a highly significant increase of Z,E-bilirubin over time (P < 0.0001), starting at 15 min. Photoisomers reached ~25% of total bilirubin concentration after 4 h. However, there were no significant differences between the three randomized groups in spite of significantly higher irradiance using double fluorescent lights vs. single fluorescent or photodiodes. CONCLUSION: Formation of bilirubin photoisomers is rapid, and occurs early during intensive phototherapy for neonatal jaundice. The rate and level of photoisomerization was not influenced by irradiance and light source.

Follow-up of extreme neonatal hyperbilirubinaemia in 5- to 10-year-old children: a Danish population-based study.

AIM: To investigate whether infants with neonatal hyperbilirubinaemia but without intermediate or advanced bilirubin encephalopathy develop long-term sequelae, with impairment of motor development, executive function, or hearing. METHOD: This nested double-cohort study included 167 exposed children (107 males, 60 females) born in Denmark 2000 to 2005 at gestational age ≥35 weeks with a total serum bilirubin ≥450 µmol/L (26.3mg/dL) and 163 age-, sex-, and gestational age-matched unexposed children (103 males, 60 females). The children were examined at a mean age of 7.7 years (SD 1.7y) using the Movement Assessment Battery for Children-Second Edition (MABC-2), pure tone audiometry, and the Behavioural Regulation Inventory of Executive Function (BRIEF) questionnaire. RESULTS: The follow-up rate was 70% of the eligible infants in the exposed group and 45% in the unexposed group. Mean difference was -0.2 (95% confidence interval [CI] -1.1 to 0.8) in adjusted standard score for MABC-2 and 0.3 (95% CI -2.9 to 3.5) in adjusted BRIEF executive composite standard score. No children had significant hearing impairment or a diagnosis of cerebral palsy, attention-deficit-hyperactive disorder, or autism spectrum disorder recorded in national registries. INTERPRETATION: No evidence was found of an increased risk of deficits in motor development, executive function, or hearing in children with extreme hyperbilirubinaemia who did not have intermediate or advanced bilirubin encephalopathy.

UGT1A1*28 polymorphism and acute lymphoblastic leukemia in children: a Danish case-control study.

BACKGROUND: Oxidative stress is a possible risk factor in the development of acute lymphoblastic leukemia (ALL) in children. Bilirubin is a potent endogenous antioxidant, and the UGT1A1*28 polymorphism is the main genetic cause of variation in plasma bilirubin in Western Europe. METHODS: In a case-control study of 665 incident cases of ALL in childhood in Denmark 1982-2010 and 1,379 controls, associations between UGT1A1*28 genotypes and ALL in childhood were estimated as odds ratios by logistic regression with adjustment for sex and birth decade. Subgroup analyses were carried out by age at onset in three groups, and on the ALL subtypes precursor B-cell, T-cell, and t(12;21) positive status. Cases were identified in The Danish Registry of Childhood Cancer, and genotypes were estimated from dried blood spots stored in The Danish Neonatal Screening Biobank. Controls were newborns with blood spots taken right before and after a case. RESULTS: We found no association between ALL in childhood and UGT1A1*28 genotypes. The odds ratio was 1.01 (0.88-1.17) for heterozygotes and 1.03 (0.78-1.36) for homozygotes. Also, no associations were found in the subgroup analyses. CONCLUSION: We found no association between the UGT1A1*28 genotypes and ALL in children.

The Danish neonatal clinical database is valuable for epidemiologic research in respiratory disease in preterm infants.

BACKGROUND: We examined the quality of the information on the use of surfactant and the use of and duration of nasal continuous positive airway pressure (nCPAP), oxygen supplementation, and mechanical ventilation in the Danish Neonatal Clinical Database (NeoBase). METHODS: We included all neonates born with a gestational age < 32 weeks admitted to a Neonatal Intensive Care Unit (NICU) at two university hospitals in 2005. On discharge, the clinicians complete a structured form with information related to the delivery and course of stay in the NICU. These forms were entered into the NeoBase. The nurses' daily bedside documentation was used as reference standard. Concordance was used as a measure of agreement between the NeoBase and the reference standard. For the dichotomous variables the concordance was defined as the sensitivity of the information registered in the NeoBase. For the continuous variables, it was based on the discrepancy in days between the NeoBase and the reference standard. The percentage of concordance was described as high (> 90), moderate (70-90) or low (< 70). RESULTS: Overall, 153 infants participated in the study. Concordance was high for all dichotomous variables. The NeoBase slightly underestimated the duration of nCPAP and mechanical ventilation. The duration of oxygen therapy was neither over- nor underestimated in the NeoBase. Concordance was low for all continuous variables if we assumed that the registered information was identical. It was 100% for duration of mechanical ventilation and moderate for nCPAP and oxygen supplementation if we allowed for a discrepancy of 1 day. CONCLUSION: The NeoBase is a valuable tool for clinical and epidemiologic research and quality assurance regarding neonatal respiratory disease.

Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels.

BACKGROUND: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. METHODS: Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010. RESULTS: Twenty-four million (18% of 134 million live births ≥ 32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments. CONCLUSION: Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

Relation between serum bilirubin levels ≥450 µmol/L and bilirubin encephalopathy; a Danish population-based study.

AIM: Describe the relation between levels of total serum bilirubin (TsB) ≥450 µmol/L and acute intermediate, acute advanced and chronic bilirubin encephalopathy. MATERIAL AND METHODS: All infants born at gestational age ≥35 weeks in Denmark between 2000 and 2007 with a TsB ≥450 µmol/L according to the national laboratory information system. Infants diagnosed with bilirubin encephalopathy were found in the Danish National Registry of Patients. RESULTS: 502,766 infants at gestational age ≥35 weeks were identified. Two hundred twenty-four developed a TsB ≥450 µmol/L, equivalent to an incidence of 45/100,000/year, and it increased during the period. Incidence of infants with peak TsB of 450-499, 500-599 and 600-1000 µmol/L were 29.6, 12.7 and 2.2 per 100,000, respectively. Three infants had acute advanced bilirubin encephalopathy and got severe sequelae, whereas the two infants with acute intermediate encephalopathy developed normally. Their peak TsB was ≥544 µmol/L. Having a peak TsB 600-1000 µmol/L, the risk of acute advanced and chronic bilirubin encephalopathy was 27% (95% CI 6;61), and the incidence of these conditions was 0.6 (95% CI 0.1;1.7) per 100,000. CONCLUSION: The incidence of infants with TsB ≥450 µmol/L was 45/100,000/year. Infants with a TsB ≥600 µmol/L had a substantial risk of developing acute advanced and chronic bilirubin encephalopathy, and the incidence of these conditions was 0.6 per 100,000.

Comparison of the transcutaneous bilirubinometers BiliCheck and Minolta JM-103 in preterm neonates.

AIM: To investigate the trueness and uncertainty of two transcutaneous bilirubinometers BiliCheck and Minolta JM-103 in preterm infants; establish cut-off values for the transcutaneous bilirubin (TcB) level, indicating the need for total serum bilirubin (TsB) measurement; and estimate how many blood samples could be saved. METHODS: In 133 neonates with gestational ages 28(+0) -34(+6) weeks, 239 measurements of TcB by BiliCheck (TcB(B)) and JM-103 (TcB(M)) and of TsB were performed. RESULTS: Median TsB of the first samples was 160 (range, 53-293) µmol/L, whereas median TcB(B) was 12 µmol/L (8%) lower and TcB(M) 67 µmol/L (40%) lower. TcB(B) underestimated TsB for TsB ≥180µmol/L. All TcB(M) values, except one, underestimated TsB. The underestimation increased with increasing TsB. Multiple regression analysis showed that post-natal age and ethnicity were confounding factors for TcB(M); none were found for TcB(B). The uncertainty was the same for the two instruments. By using cut-off values of 70% of the phototherapy limit for TcB(B) and 35% for TcB(M), the sensitivity of the screening would be 95% and 97%, and 36% and 24% of the blood samples could be saved, respectively. CONCLUSION: TcB determined with JM-103 gave values much lower than those obtained with BiliCheck. The underestimation of TsB increased with increasing concentrations. By using transcutaneous bilirubinometers in preterm neonates, 24-36% of the blood samples could be saved.