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1.
Acta Paediatr ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38924152

ABSTRACT

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.

2.
Int J Mol Sci ; 24(1)2022 Dec 27.
Article in English | MEDLINE | ID: mdl-36613904

ABSTRACT

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.


Subject(s)
Hyperbilirubinemia, Neonatal , Photochemotherapy , Infant, Newborn , Humans , Phototherapy/methods , Light , Hyperbilirubinemia, Neonatal/therapy , Lighting
3.
Pediatr Res ; 92(3): 816-821, 2022 09.
Article in English | MEDLINE | ID: mdl-34789840

ABSTRACT

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.


Subject(s)
Digestive System Diseases , Hyperbilirubinemia, Neonatal , Jaundice, Neonatal , Action Spectrum , Bilirubin , Humans , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Light , Phototherapy
4.
Acta Paediatr ; 110(6): 1935-1941, 2021 06.
Article in English | MEDLINE | ID: mdl-33560519

ABSTRACT

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.


Subject(s)
Glucosephosphate Dehydrogenase Deficiency , Hyperbilirubinemia, Neonatal , Jaundice, Neonatal , Child , Denmark/epidemiology , Exchange Transfusion, Whole Blood , Glucosephosphate Dehydrogenase , Glucosephosphate Dehydrogenase Deficiency/ethnology , Glucosephosphate Dehydrogenase Deficiency/genetics , Humans , Infant , Infant, Newborn , Middle East/ethnology , Retrospective Studies
5.
Semin Perinatol ; 45(1): 151358, 2021 02.
Article in English | MEDLINE | ID: mdl-33358025

ABSTRACT

The effectiveness of phototherapy for neonatal hyperbilirubinemia based on Danish clinical trials is presented. Randomized controlled trials on the quality of light showed that blue-green fluorescent light (peak emission at 490 nm) was more efficient than blue fluorescent light (peak emission at 452 nm); blue-green light-emitting diode (LED) light (peak emission at 478 nm) was more efficient than blue LED light (peak emission at 459 nm); and blue-green LED light (peak emission at 497 nm) was equivalent to blue LED light (peak emission at 459 nm). Bilirubin-reducing effects correlated with irradiance, dependent on hemoglobin concentration, and independent of rotating infants. Phototherapy from both above and below was more efficient than therapy applied only from above at high levels of irradiance. In conclusion, we estimate and recommend the use of blue-green LED light (peak emission at 480 nm) rather than blue light (peak emission at 460 nm) for treating of neonatal hyperbilirubinemia.


Subject(s)
Hyperbilirubinemia, Neonatal , Jaundice, Neonatal , Bilirubin , Clinical Trials as Topic , Denmark , Humans , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Phototherapy , Randomized Controlled Trials as Topic
6.
Pediatr Res ; 90(1): 74-81, 2021 07.
Article in English | MEDLINE | ID: mdl-33173174

ABSTRACT

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.


Subject(s)
ABO Blood-Group System/immunology , Autoantibodies/immunology , Blood Group Incompatibility/complications , Erythroblastosis, Fetal/immunology , Hyperbilirubinemia, Neonatal/immunology , Immunoglobulin G/immunology , Infant, Newborn, Diseases , Adult , Case-Control Studies , Female , Humans , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Male , Phototherapy , Pregnancy
7.
Pediatr Res ; 89(3): 598-603, 2021 02.
Article in English | MEDLINE | ID: mdl-32335581

ABSTRACT

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.


Subject(s)
Hyperbilirubinemia, Neonatal/blood , Light , Phototherapy/methods , Bilirubin/blood , Denmark , Female , Gestational Age , Humans , In Vitro Techniques , Infant, Newborn , Male , Serum Albumin, Human
8.
J Perinatol ; 41(1): 157-163, 2021 01.
Article in English | MEDLINE | ID: mdl-33070153

ABSTRACT

OBJECTIVES: Investigate characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. STUDY DESIGN: Using a cohort design, we identified term infants evaluated for EOS with blood, cerebrospinal fluid, or urine cultures in 326 NICUs (2011-2016). Using multivariable logistic regression, we investigated the association between EOS and demographic characteristics. RESULTS: Of 142,410 infants, 1197 (0.8%) had EOS, most commonly caused by group B Streptococcus (GBS; 40.6%). Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age <19 years, vasopressor treatment, and ventilator support. CONCLUSION(S): GBS was the most frequent cause of EOS. Early risk factor recognition may help daily management of term infants in NICUs.


Subject(s)
Intensive Care Units, Neonatal , Sepsis , Adult , Anti-Bacterial Agents/therapeutic use , Cesarean Section , Female , Humans , Infant , Infant, Newborn , Pregnancy , Risk Factors , Sepsis/diagnosis , Sepsis/drug therapy , Sepsis/epidemiology , Streptococcus agalactiae , Young Adult
10.
Ugeskr Laeger ; 182(14A)2020 03 30.
Article in Danish | MEDLINE | ID: mdl-32285792

ABSTRACT

Approximately 60% of term newborn infants are jaundiced during the first week of life, which is caused by unconjugated bilirubin. Bilirubin encephalopathy is seen with severe hyperbilirubinaemia, when unbound bilirubin crosses the blood-brain barrier. The chronic form is called kernicterus spectrum disorder. To avoid this devastating condition, the treatment of choice for neonatal hyperbilirubinaemia is phototherapy, which is most efficient with LED light of 478-nm wavelength. In this review, we argue, that a systematic approach to hyperbilirubinaemic infants as well as surveillance of extreme neonatal hyperbilirubinaemia is highly important.


Subject(s)
Hyperbilirubinemia, Neonatal , Jaundice, Neonatal , Kernicterus , Bilirubin , Denmark/epidemiology , Humans , Hyperbilirubinemia, Neonatal/diagnosis , Hyperbilirubinemia, Neonatal/epidemiology , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Kernicterus/epidemiology , Kernicterus/etiology , Kernicterus/prevention & control , Phototherapy
11.
J Perinatol ; 40(2): 194-202, 2020 02.
Article in English | MEDLINE | ID: mdl-31907395

ABSTRACT

OBJECTIVE: To determine the incidence and etiology of extreme neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥450 µmol/L, and kernicterus spectrum disorder (KSD) in Denmark between 2000 and 2015. STUDY DESIGN: We identified all infants born between 01.01.2000 and 31.12.2015 with TSB ≥450 µmol/L, ratio of conjugated to TSB <0.30, gestational age ≥35 weeks, and postnatal age ≤4 weeks, using Danish hospitals' laboratory databases. RESULT: We included 408 infants. The incidence of extreme neonatal hyperbilirubinemia among infants with gestational age ≥35 weeks was 42/100,000 during the study period with a seemingly decreasing incidence between 2005 and 2015. Twelve of the 408 infants developed KSD, (incidence 1.2/100,000) Blood type ABO isohemolytic disease was the most common explanatory etiology. CONCLUSIONS: Our study stresses the importance of a systematic approach to neonatal jaundice and ongoing surveillance of extreme neonatal hyperbilirubinemia and KSD.


Subject(s)
Hyperbilirubinemia, Neonatal/epidemiology , Kernicterus/epidemiology , Bilirubin/blood , Cohort Studies , Denmark/epidemiology , Exchange Transfusion, Whole Blood , Female , Gestational Age , Glucosephosphate Dehydrogenase Deficiency/epidemiology , Humans , Hyperbilirubinemia, Neonatal/complications , Hyperbilirubinemia, Neonatal/therapy , Incidence , Infant, Newborn , Jaundice, Neonatal , Kernicterus/diagnosis , Kernicterus/etiology , Magnetic Resonance Imaging , Male , Phototherapy
12.
Acta Paediatr ; 109(2): 280-284, 2020 02.
Article in English | MEDLINE | ID: mdl-31197878

ABSTRACT

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.


Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Amniotic Fluid , Female , Humans , Infant, Newborn , Lung , Phosphatidylcholines , Pregnancy , Respiratory Distress Syndrome, Newborn/diagnosis , Spectrum Analysis , Sphingomyelins
13.
J Perinatol ; 40(2): 180-193, 2020 02.
Article in English | MEDLINE | ID: mdl-31420582

ABSTRACT

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.


Subject(s)
Jaundice, Neonatal/therapy , Phototherapy , History, 15th Century , History, 18th Century , History, 20th Century , History, 21st Century , Humans , Hyperbilirubinemia, Neonatal/history , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/therapy , Infant, Very Low Birth Weight , Jaundice, Neonatal/history , Phototherapy/adverse effects , Phototherapy/instrumentation , Quality Control
14.
Acta Ophthalmol ; 98(2): 166-171, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31421027

ABSTRACT

PURPOSE: To investigate outcomes of routine vision screening compared to as-indicated ophthalmological investigation of all children born preterm in a Danish region from 1997 to 2014. METHODS: All children born preterm (gestation age < 32 weeks or birthweight < 1500 g) screened for retinopathy of prematurity (ROP) were divided into two groups. From 1997 to 2009, only children treated for ROP or referred for visual problems received ophthalmological investigation (as-indicated group). From 2010 to 2014, all ROP-screened infants were offered ophthalmological investigation at 6 months and 3 years of age (screening group). RESULTS: A total of 560 children were included in the as-indicated period, 41 and 87 were referred for ophthalmological investigation at 6 months and 3 years, respectively. In the screening period, 295 children were included, 251 and 150 of whom underwent vision evaluation at 6 months and 3 years, respectively. Mean visual acuity was 4.1 cycles per degree with Teller acuity cards at 6 months and 0.78 decimal at 3 years. At 3 years, 2.7%(n = 11) in the as-indicated versus 3.5%(n = 10) screening group had visual acuity < 6/18 (p = 0.24). Cerebral palsy (n = 28) and epilepsy (n = 5) were significantly related to vision impairment (p = 0.001/0.006), while treated ROP was not (n = 13). Refractive error was common at 3 years (61%), especially astigmatism (50%). Gestational age, birthweight and ROP were not associated with vision impairment or refractive error. CONCLUSION: Screening preterm children at 6 months and 3 years did not reveal more visually impaired children compared to examination when indicated.


Subject(s)
Premature Birth , Retinopathy of Prematurity/diagnosis , Vision Screening/methods , Birth Weight , Child, Preschool , Denmark , Diagnostic Tests, Routine , Female , Follow-Up Studies , Gestational Age , Humans , Infant , Infant, Premature , Male , Retinopathy of Prematurity/physiopathology , Retrospective Studies , Vision Screening/instrumentation , Visual Acuity/physiology
15.
Acta Paediatr ; 109(2): 285-290, 2020 02.
Article in English | MEDLINE | ID: mdl-31038796

ABSTRACT

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.


Subject(s)
Respiratory Distress Syndrome, Newborn , Sphingomyelins , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Phosphatidylcholines , Pregnancy , Respiratory Distress Syndrome, Newborn/diagnosis , Spectrum Analysis
16.
JAMA Pediatr ; 172(9): 824-831, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30039171

ABSTRACT

Importance: Nasal continuous positive airway pressure (nCPAP) is a well-established treatment of respiratory distress syndrome in preterm infants. Suboptimal weaning from nCPAP may be associated with lung injury, pulmonary morbidity, and infant weight gain. To our knowledge, the best weaning strategy from nCPAP is unknown. Objective: To compare the effect of sudden wean and pressure wean from nCPAP in very preterm infants. Design, Setting, and Participants: A randomized, clinical, open-label, multicenter trial was conducted at 6 neonatal intensive care units in Denmark from September 2012 to December 2016 and included infants born before 32 weeks of gestation. Interventions: Sudden wean with discontinuation of nCPAP without a prior reduction in pressure. Pressure wean with gradual pressure reduction prior to the discontinuation of nCPAP. Main Outcome and Measures: The primary outcome was weight gain velocity from randomization to postmenstrual age 40 weeks. Secondary outcomes included other measures of growth, nCPAP and the duration of oxygen supplementation, postmenstrual age at successful wean and at discharge, successful wean at the first attempt, the number of attempts to wean, and the length of the hospital stay. Prespecified subgroup analyses by gestational age were performed. Results: Of the 372 randomized infants, 185 (49.7%) were randomized to sudden wean and 187 infants (50.3%) to pressure wean. A total of 177 infants in both groups completed the trial (median gestational age for sudden and pressure wean, 30 weeks [interquartile range, 29-31]; male: sudden wean, 89 [50%]; pressure wean, 96 [54%]). There was no difference in mean [SD] weight gain velocity from randomization to 40 weeks postmenstrual age between the 2 groups (22 [6] g/kg/day). No difference was found in any of the secondary outcomes. More infants born before 28 weeks of gestation were successfully weaned from nCPAP during the first attempt in the pressure wean group compared with the sudden wean group (risk difference, 31%; 95% CI, 13%-50%), but there was no difference in the duration of nCPAP and oxygen supplementation. Conclusions and Relevance: Overall, we found no difference in weight gain velocity or any of the secondary outcomes between very preterm infants who were randomized to sudden wean or pressure wean from nCPAP. However, among infants born before 28 weeks' gestation, infants from the pressure wean group were more often successfully weaned during the first attempt without a longer total duration of nCPAP treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01721629.


Subject(s)
Continuous Positive Airway Pressure/methods , Infant, Premature , Length of Stay/statistics & numerical data , Respiratory Distress Syndrome, Newborn/therapy , Ventilator Weaning/methods , Denmark , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Male , Treatment Outcome
17.
Pediatr Res ; 84(2): 228-232, 2018 08.
Article in English | MEDLINE | ID: mdl-29892033

ABSTRACT

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.


Subject(s)
Bilirubin/blood , Galactosemias/complications , Hyperbilirubinemia, Neonatal/blood , Kernicterus/blood , Adolescent , Brain Diseases/blood , Brain Diseases/complications , Child , Child, Preschool , Cohort Studies , Denmark/epidemiology , Female , Follow-Up Studies , Humans , Hyperbilirubinemia, Neonatal/complications , Infant , Infant, Newborn , Kernicterus/complications , Male , Mutation , Phototherapy , Retrospective Studies
18.
PLoS One ; 13(6): e0197938, 2018.
Article in English | MEDLINE | ID: mdl-29856793

ABSTRACT

BACKGROUND: Hyperbilirubinemia is a common problem in neonates that can progress into kernicterus. Suspected neonatal hyperbilirubinemia is a common reason for contact with the healthcare system. The severity and management of jaundice are determined based on estimated bilirubin levels. However, no easy and accessible tool for self-assessing neonatal jaundice is currently available. Smartphones could potentially be transformed into a medical device that could be used by both patients and practitioners. OBJECTIVE: To investigate whether a digital image produced by a camera embedded on a smartphone can be a used as a screening tool for neonatal hyperbilirubinemia. STUDY DESIGN: A total of 64 randomly selected newborns were enrolled. The inclusion criteria were healthy Caucasians, gestational age >35 weeks, age >24 hours and ≤14 days old, and parental informed consent. The exclusion criteria were facial skin lesions and light treatment. Images of the glabella were obtained with an iPhone 6 via i) directly applied pressure, ii) a dermatoscope, or iii) a dermatoscope equipped with a Wratten No. 11 filter. The red, green and blue colour intensities of each image were compared to bilirubin levels. RESULTS: Only the dermatoscope-acquired intensities of the green and blue channels were significantly correlated (p < 0.001) with bilirubin measurements (Pearson's r: 0.59 and 0.48, respectively). For the green and blue channels, discrimination limits of 212 and 190, respectively, revealed a sensitivity and specificity of 100% and 62.5%, respectively, for green and 90.9% and 60%, respectively, for blue for a plasma bilirubin above 205 µmol/L. CONCLUSIONS: The results of this study indicate that a smartphone equipped with a consistent light source in the form of a dermatoscope may be a simple screening tool for neonatal hyperbilirubinemia. However, the method requires some improvement before clinical application.


Subject(s)
Bilirubin/blood , Blood Chemical Analysis/instrumentation , Skin , Smartphone/instrumentation , Female , Humans , Hyperbilirubinemia, Neonatal/blood , Hyperbilirubinemia, Neonatal/diagnosis , Infant, Newborn , Male
19.
Pediatr Res ; 82(6): 947-951, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28876328

ABSTRACT

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.


Subject(s)
Hemoglobins/metabolism , Hyperbilirubinemia, Neonatal/therapy , Phototherapy , Bilirubin/blood , Female , Humans , Hyperbilirubinemia, Neonatal/blood , Infant, Newborn , Male , Prospective Studies
20.
Curr Pediatr Rev ; 13(3): 176-180, 2017.
Article in English | MEDLINE | ID: mdl-28721812

ABSTRACT

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.


Subject(s)
Jaundice, Neonatal/therapy , Phototherapy/methods , Bilirubin/analogs & derivatives , Humans , Infant, Newborn , Phototherapy/adverse effects
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