Phototherapy Alters the Plasma Metabolite Profile in Infants Born Preterm with Hyperbilirubinemia.

OBJECTIVE: To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB). STUDY DESIGN: From a cohort of prospectively enrolled infants born preterm (n = 92), plasma samples of very preterm (VPT; GA, 28 + 0 to 31 + 6 weeks, n = 27) and moderate/late preterm (M/LPT; GA, 32 + 0 to 35 + 6 weeks, n = 33) infants requiring phototherapy for NHB were collected prior to the initiation of phototherapy and 24 hours after starting phototherapy. An additional sample was collected 48 hours after starting phototherapy in a randomly selected subset (n = 30; VPT n = 15; M/LPT n = 15). Metabolite profiles were determined using ultraperformance liquid chromatography tandem mass spectroscopy. Two-way ANCOVA was used to identify metabolites that differed between GA groups and timepoints after adjusting for total serum bilirubin levels (false discovery rate q-value < 0.05). Top impacted pathways were identified using pathway over-representation analysis. RESULTS: Phototherapy was initiated at lower total serum bilirubin (mean ± SD mg/dL) levels in VPT compared with M/LPT infants (7.3 ± 1.4 vs 9.9 ± 1.9, P < .01). We identified 664 metabolites that were significant for a phototherapy effect, 191 metabolites significant for GA, and 46 metabolites significant for GA × phototherapy interaction (false discovery rate q-value < 0.05). Longer duration phototherapy had a larger mean effect size (24 hours postphototherapy: d = 0.36; 48 hours postphototherapy: d = 0.43). Top pathways affected by phototherapy included membrane lipid metabolism, one-carbon metabolism, creatine biosynthesis, and oligodendrocyte differentiation. CONCLUSION: Phototherapy alters the plasma metabolite profile more than GA in preterm infants with NHB, affecting pathways related to lipid and one-carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation.

Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Light-Emitting Diode (LED) Phototherapy versus Non-LED Phototherapy Devices for Hyperbilirubinemia in Neonates: A Systematic Review and Meta-analysis.

This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39-0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: -8.07, 95% CI: -8.45 to -7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: -0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources. KEY POINTS: · The efficacy of phototherapy is dependent on specific characteristics of light sources of phototherapy devices.. · LED phototherapy demonstrated better efficacy with shorter duration and lower rate of treatment failure.. · Adverse effects of phototherapy devices such as hypothermia, hyperthermia, and skin rash should be monitored..

Use of prophylactic phototherapy for RhD neonatal disease in a referral service.

OBJECTIVE: This study aimed to describe the effect of prophylactic phototherapy in the treatment of infants with Neonatal Hemolytic Disease. METHOD: A retrospective cohort study was carried out with 199 RhD-positive infants, born to RhD-negative mothers, alloimmunized for RhD antigen, between January 2009 and December 2018. RESULTS: The incidence of exchange transfusions in the study population was 9.5%, with a mean maximum bilirubin value of 11.3 mg % (± 4.3mg %). Bilirubin's maximum peak was achieved with a mean of 119.2 life hours (± 70.6h). CONCLUSION: The low incidence of exchange transfusion, the extended maximum bilirubin peak for later ages, and the low mean of the maximum bilirubin values may indicate a positive effect of prophylactic phototherapy in the treatment of this disease. Further studies must be carried out to confirm these findings.

An End-Tidal Carbon Monoxide Nomogram for Term and Late-Preterm Chinese Newborns.

OBJECTIVE: To establish a reference nomogram for end-tidal CO corrected for ambient CO (ETCOc) levels in term and late-preterm Chinese newborns and then assess its efficacy to identify hemolytic hyperbilirubinemia. STUDY DESIGN: We conducted a prospective study by measuring concurrent ETCOc and total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels collected postnatally at 12, 24, 48, 72, 96, and 120 hours of age. ETCOc at the 25th, 50th, 75th, and 95th percentiles at each epoch were used to construct the reference nomogram. We then explored the ability of predischarge ETCOc and TSB/TcB metrics to predict the development of hyperbilirubinemia requiring phototherapy in early postnatal period and jaundice readmission in late postnatal period. RESULTS: Our nomogram, based on 990 measurements from 455 infants who were not nonhemolytic, displayed a steady line within 3 postnatal days, followed by a subsequent decline. From a cohort of infants with a serial ETCOc measurements (n = 130) and those readmitted (n = 21), we found that ETCOc and TSB/TcB ≥75th percentile can identify most hemolytic hyperbilirubinemia between 12 and 72 hours after birth with an area under the curve (AUC) of 0.741. An ETCOc ≥1.7 ppm alone between 96 and 120 hours after birth can identify most hemolytic hyperbilirubinemia with an AUC of 0.816. In addition, 90.5% of readmitted infants had an ETCOc ≥75th percentile. CONCLUSIONS: An ETCOc reference nomogram during the first 5 postnatal days in nonhemolytic term and late-preterm newborns can be used to identify hemolytic hyperbilirubinemia requiring phototherapy in the early postnatal period and readmission in the late postnatal period.

Association Between Neonatal Phototherapy Exposure and Childhood Neoplasm.

OBJECTIVE: To study the association between phototherapy for the treatment of neonatal jaundice and the risk of childhood neoplasms. STUDY DESIGN: This population-based retrospective cohort study included all infants born at ≥32 weeks of gestation at a single medical center between 1988 and 2018. The incidence of neoplastic diseases was compared between infants exposed to phototherapy and those unexposed. Kaplan-Meier curves and log-rank tests were used for cumulative incidence comparison, and multivariable Cox and Weibull survival analysis were used to adjust for confounding or clinically significant variables. RESULTS: The study population included 342 172 infants, of whom 18 797 (5.5%) were exposed to phototherapy. The median duration of follow-up was 9.5 years (range, birth to 18 years). Phototherapy was associated with a significantly increased risk for childhood malignancies and benign tumors (preterm birth and maternal age-adjusted hazard ratio, 1.89 [95% CI, 1.35-2.67] for malignancies and 1.27 [95% CI, 1.02-1.57] for benign tumors) Specifically, phototherapy was associated with hematopoietic cancers and leukemia (hazard ratio, 2.29 [95% CI, 1.48-3.54; P < .01] for hematopoietic cancers and 2.51 [95% CI, 1.52-4.14; P < .001] for leukemia), but not with solid tumors and lymphoma. CONCLUSIONS: Phototherapy may be associated with a slightly increased childhood risk of neoplasm. It is important to strictly follow phototherapy treatment guidelines to minimize unnecessary exposure.

Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project.

OBJECTIVE: To investigate the clinical and genetic causes of neonatal unconjugated hyperbilirubinemia. STUDY DESIGN: We included 1412 neonates diagnosed with unconjugated hyperbilirubinemia (total serum bilirubin >95 percentile for age), from the China Neonatal Genomes Project between August 2016 and September 2019, in the current study. Clinical data and targeted panel sequencing data on 2742 genes including known unconjugated hyperbilirubinemia genes were analyzed. RESULTS: Among the 1412 neonates with unconjugated hyperbilirubinemia, 37% had severe unconjugated hyperbilirubinemia, with total serum bilirubin levels that met the recommendations for exchange transfusion. Known clinical causes were identified for 68% of patients. The most common clinical cause in the mild unconjugated hyperbilirubinemia group was infection (17%) and in the severe group was combined factors (21%, with infection combined with extravascular hemorrhage the most common). A genetic variant was observed in 55 participants (4%), including 45 patients with variants in genes associated with unconjugated hyperbilirubinemia and 10 patients with variants that were regarded as additional genetic findings. Among the 45 patients identified with unconjugated hyperbilirubinemia-related variants, the genes were mainly associated with enzyme deficiencies, metabolic/biochemical disorders, and red blood cell membrane defects. G6PD and UGT1A1 variants, were detected in 34 of the 45 patients (76%). CONCLUSIONS: Known clinical causes, which varied with bilirubin levels, were identified in approximately two-thirds of the patients. Genetic findings were identified in 4% of the patients, including in patients with an identified clinical cause, with G6PD and UGT1A1 being the most common genes in which variants were detected.

Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences. STUDY DESIGN: Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated. RESULTS: Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and methane (CH4) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH4. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO, NO2, nonmethane hydrocarbon, and CH4 exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH4. A positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO2, nonmethane hydrocarbon, CH4 exposure, and serum hemoglobin levels was noted in male newborns. CONCLUSION: Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.

Nursing diagnosis neonatal hyperbilirubinemia: A survival analysis.

PURPOSE: To analyze the short-term survival of the nursing diagnosis of neonatal hyperbilirubinemia in hospitalized neonates within the first 24 h of life and over a maximum of 7 days. METHODS: A prospective open cohort study with a longitudinal design was developed with 120 newborns during the first 24 h of life. The survival rate after a nursing diagnosis of neonatal hyperbilirubinemia was analyzed for 7 days. FINDINGS: The number of new cases of neonatal hyperbilirubinemia during the follow-up was 82 (RR: 90.1%, daily incidence rate: 34.17%). The greatest manifestation of the diagnosis occurred in the first three days (n = 97). The median diagnostic survival time was 2 days (95% CI: 2-2). Yellow-orange skin color (RR = 8.08), yellow mucous membranes (RR = 2.05), yellow sclera (RR = 1.99), and female gender (RR = 1.36) had the highest risk ratios. CONCLUSIONS: A rapid impairment of neonatal hyperbilirubinemia in hospitalized neonates was observed. Some clinical indicators were associated with an increased risk for this diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Studies on the prognostic capacity of the clinical indicators of nursing diagnoses like neonatal hyperbilirubinemia strengthen the clinical reasoning of nurses and subsidize diagnostic inferences and accurate clinical decisions.

Enfermedad hemolítica del feto y del recién nacido por aloanticuerpos contra el antígeno M / Hemolytic disease in fetuses and newborns due to antibodies against the M-antigen

Resumen | Hay pocos reportes de enfermedad hemolítica del feto y del recién nacido causada por aloanticuerpos contra el sistema de antígenos MNS, especialmente, porque los anticuerpos que se generan contra estos antígenos son del tipo IgM, los cuales tienen reactividad a temperaturas inferiores a los 37 °C, y, por lo tanto, no son de importancia clínica. A pesar de ello, se han reportado casos con presencia de anticuerpos anti-M de tipo IgG causantes de la enfermedad hemolítica del recién nacido e, incluso, casos de muerte intrauterina por incompatibilidad materno-fetal en el sistema MNS. El proceso hemolítico se asemeja al causado por los anticuerpos anti-Kell, con anemia progresiva por supresión hematopoyética que induce la destrucción de precursores hematopoyéticos en la médula ósea y ausencia de reticulocitos en la periferia. Se reporta el caso de una mujer con 38,5 semanas de gestación, que presentó discrepancia en la hemoclasificación directa y en la inversa. Como resultado, el recién nacido fue positivo en la prueba de Coombs directa sin que existiera incompatibilidad ABO con la madre. La correlación de estos resultados llevó a la detección de un anticuerpo anti-M en el suero materno. El diagnóstico definitivo fue posible gracias a la discrepancia en la hemoclasificación de la sangre materna. A pesar de que los anticuerpos anti-M usualmente no desempeñan un papel importante en la enfermedad hemolítica perinatal, este caso resalta la importancia de determinar la presencia de diferentes anticuerpos que pueden ser de vital interés a la hora de prevenir resultados graves asociados con dicha condición. Además, abre la puerta a nuevas recomendaciones relacionadas con la tamización y el tratamiento temprano de la hemólisis en los recién nacidos.

Abstract | There are few case reports of hemolytic disease in fetuses and newborns (HDFN) caused by alloantibodies against the MNS blood group system. The reason for this dearth is that antibodies toward these antigens are usually IgM, which not only cannot cross the placental circulation but also react at temperatures below 37°C. They are, therefore, of minimal clinical importance. Nevertheless, cases have been reported in which the presence of anti-M IgG antibodies caused severe HDFN and even intrauterine death in the presence of maternal-fetal MNS incompatibility indicating that they could have a high clinical impact. The hemolytic pattern observed in these cases is similar to that caused by anti-Kell antibodies. Progressive anemia is mediated and developed through hematopoietic suppression inducing the destruction of bone marrow precursor cells with the resulting absence of reticulocytes in peripheral blood. This occurred in the case of a woman at 38.5 weeks of gestation who showed a discrepancy between direct and reverse blood type determination. A direct Coombs test was performed on the newborn's blood, which was positive in the absence of maternal-fetal ABO incompatibility. Further tests were performed and anti-M antibodies were found in the maternal serum screening. Our final diagnosis was largely due to discrepancy issues in maternal blood. Although anti-M antibodies do not usually play a significant role in HDFN, this case stresses the importance of identifying the presence of antibodies that can be crucial in preventing HDFN and lead to new recommendations for the screening and prompt treatment of hemolysis in newborns.

El contacto piel a piel como promotor de la lactancia materna, y su posible relación con la disminución de la hiperbilirrubinemia / Skin-to-skin contact as a promoter of breastfeeding, and its possible relationship with the reduction of hyperbilirubinemia

INTRODUCCIÓN: El contacto piel a piel (CPP) postparto es una práctica de atención de salud fuertemente aconsejada por la OMS, por los beneficios a largo y a corto plazo que conlleva tanto para la salud de la madre como para la del recién nacido. OBJETIVO: Realizar una búsqueda bibliográfica con el objetivo de determinar los beneficios que tiene la CPP durante el periodo del postparto inmediato sobre la lactancia materna (LM) y la ictericia neonatal (IN). RESULTADOS: Los resultados muestran que el CPP aumenta diversos indicadores de éxito de lactancia materna, dentro de los cuales destacan: aumento en la efectividad de la primera lactancia, mayor probabilidad de mantener la LM a 4 meses, aumento del periodo de LM en promedio, mayor probabilidad de LM exclusiva a 6 meses. No se encontraron mayores beneficios al iniciar el CPP antes de los 10 minutos, ni al prolongarlo más de 60 minutos. Además, el CPP indirectamente disminuye la probabilidad de presentar IN, debido a que aumenta la frecuencia de LM, indicador que se asocia de manera indirecta a los niveles de bilirrubina en el recién nacido. CONCLUSIÓN: La revisión de la literatura especializada nos permite concluir que el contacto temprano entre la madre y su hijo en sala de partos, piel a piel, tiene efectos significativamente positivos en la lactancia materna y puede llegar a representar un factor protector de la hiperbilirrubinemia no conjugada en el RN.

Postpartum skin-to-skin contact (SSC) is a health care practice strongly advised by the WHO because of the long- and short-term benefits for both maternal and newborn health. This update summarizes the main findings supporting the recommendation to perform SSC during the immediate postpartum period, specifically the benefits on breastfeeding (BF) and neonatal jaundice (NI). The results show that SSC increases several indicators of breastfeeding success, including: increased effectiveness of the first breastfeeding, greater probability of maintaining BF at 4 months, increased BF period on average, greater probability of exclusive BF at 6 months. No greater benefits were found when initiating SSC before 10 minutes, nor when prolonging it for more than 60 minutes. In addition, SSC indirectly decreases the probability of presenting NI, because it increases the frequency of BF, an indicator that is indirectly associated with bilirubin levels in the newborn. CONCLUSION: A review of the specialized literature allows us to conclude that postpartum skin-to-skin contact (SSC) has significantly positive effects on breastfeeding and may represent benefits in bilirubin levels in the newborn.

Cord blood bilirubin and prediction of neonatal hyperbilirubinemia and perinatal infection in newborns at risk of hemolysis

Abstract Objective To assess the accuracy of umbilical cord bilirubin values to predict jaundice in the first 48 h of life and neonatal infection. Method Newborn infants treated at a regional well-baby nursery born at ≥36 weeks of gestation were included in this retrospective cohort study. All infants born in a 3-year period from mothers with O blood type and/or Rh-negative were included and had the umbilical cord bilirubin levels measured. Hyperbilirubinemia in the first 48 h was defined as bilirubin levels above the phototherapy threshold. Neonatal infection was defined as any antibiotic treatment before discharge. Results A total of 1360 newborn infants were included. Two hundred and three (14.9%) newborn infants developed hyperbilirubinemia in the first 48 h of life. Hyperbilirubinemic infants had smaller birth weight, higher levels of umbilical cord bilirubin, a higher rate of infection and were more often direct antiglobulin test positive. Umbilical cord bilirubin had a sensitivity of 76.85% and a specificity of 69.58% in detecting hyperbilirubinemia in the first 48 h, with the cut-off value at 34 µmol/L. The area under the receiver operating characteristic curve was 0.80 (95% CI: 0.78-0.82). Umbilical cord bilirubin had a sensitivity of 27.03% and specificity of 91.31% in detecting perinatal infection. The area under the receiver operating characteristic (ROC) curve was 0.59 (95% CI: 0.57-0.63). Conclusions A positive correlation was found between umbilical cord bilirubin and hyperbilirubinemia in the first 48 h of life. Umbilical cord bilirubin is a poor marker for predicting neonatal infection.