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1.
Am J Clin Nutr ; 115(4): 1092-1104, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34982820

RESUMO

BACKGROUND: Newborn oil massage is a widespread practice. Vigorous massage with potentially harmful products and forced removal of vernix may disrupt skin barrier integrity. Hospitalized, very-preterm infants treated with sunflower seed oil (SSO) have demonstrated improved growth but community-based data on growth and health outcomes are lacking. OBJECTIVES: We aimed to test whether SSO therapy enhances neonatal growth and reduces morbidity at the population level. METHODS: We conducted an open-label, controlled trial in rural Uttar Pradesh, India, randomly allocating 276 village clusters equally to comparison (usual care) and intervention comprised of promotion of improved massage practices exclusively with SSO, using intention-to-treat and per-protocol mixed-effects regression analysis. RESULTS: We enrolled 13,478 and 13,109 newborn infants in demographically similar intervention and comparison arms, respectively. Adherence to exclusive SSO increased from 22.6% of intervention infants enrolled in the first study quartile to 37.2% in the last quartile. Intervention infants gained significantly more weight, by 0.94 g · kg-1 · d-1 (95% CI: 0.07, 1.82 g · kg-1 · d-1, P = 0.03), than comparison infants by intention-to-treat analysis. Restricted cubic spline regression revealed the largest benefits in weight gain (2-4 g · kg-1 · d-1) occurred in infants weighing <2000 g at birth. Weight gain in intervention infants was higher by 1.31 g · kg-1 · d-1 (95% CI: 0.17, 2.46 g · kg-1 · d-1; P = 0.02) by per-protocol analysis. Morbidities were similar by intention-to-treat analysis but in per-protocol analysis rates of hospitalization and of any illness were reduced by 36% (OR: 0.64; 95% CI: 0.44, 0.94; P = 0.02) and 44% (OR: 0.56; 95% CI: 0.40, 0.77; P < 0.001), respectively, in treated infants. CONCLUSIONS: SSO therapy improved neonatal growth, and reduced morbidities when applied exclusively, across the facility-community continuum of care at the population level. Further research is needed to improve demand for recommended therapy inside hospital as well as in community settings, and to confirm these results in other settings.This trial was registered at www.isrctn.com as ISRCTN38965585 and http://ctri.nic.in as CTRI/2014/12/005282.


Assuntos
Emolientes , Recém-Nascido Prematuro , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Morbidade , Óleo de Girassol
2.
PLoS Med ; 18(9): e1003680, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34582448

RESUMO

BACKGROUND: Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. METHODS AND FINDINGS: This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. CONCLUSIONS: In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility-community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry-India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.


Assuntos
Emolientes/uso terapêutico , Mortalidade Infantil , Óleo de Girassol/uso terapêutico , Administração Tópica , Adulto , Análise por Conglomerados , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Massagem , Mostardeira , Óleos de Plantas/uso terapêutico , Creme para a Pele/uso terapêutico , Fatores Socioeconômicos , Óleo de Girassol/administração & dosagem
4.
Nutrients ; 12(5)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365850

RESUMO

Necrotizing Enterocolitis (NEC) is associated with prematurity, enteral feedings, and enteral dysbiosis. Accordingly, we hypothesized that along with nutritional variability, metabolic dysfunction would be associated with NEC onset. Methods: We queried a multicenter longitudinal database that included 995 preterm infants (<32 weeks gestation) and included 73 cases of NEC. Dried blood spot samples were obtained on day of life 1, 7, 28, and 42. Metabolite data from each time point included 72 amino acid (AA) and acylcarnitine (AC) measures. Nutrition data were averaged at each of the same time points. Odds ratios and 95% confidence intervals were calculated using samples obtained prior to NEC diagnosis and adjusted for potential confounding variables. Nutritional and metabolic data were plotted longitudinally to determine relationship to NEC onset. Results: Day 1 analyte levels of alanine, phenylalanine, free carnitine, C16, arginine, C14:1/C16, and citrulline/phenylalanine were associated with the subsequent development of NEC. Over time, differences in individual analyte levels associated with NEC onset shifted from predominantly AAs at birth to predominantly ACs by day 42. Subjects who developed NEC received significantly lower weight-adjusted total calories (p < 0.001) overall, a trend that emerged by day of life 7 (p = 0.020), and persisted until day of life 28 (p < 0.001) and 42 (p < 0.001). Conclusion: Premature infants demonstrate metabolic differences at birth. Metabolite abnormalities progress in parallel to significant differences in nutritional delivery signifying metabolic dysfunction in premature newborns prior to NEC onset. These observations provide new insights to potential contributing pathophysiology of NEC and opportunity for clinical care-based prevention.


Assuntos
Aminoácidos/metabolismo , Enterocolite Necrosante/etiologia , Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Recém-Nascido Prematuro/metabolismo , Doenças Metabólicas/etiologia , Distúrbios Nutricionais/etiologia , Estado Nutricional , Análise de Dados , Bases de Dados como Assunto , Enterocolite Necrosante/prevenção & controle , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Doenças Metabólicas/metabolismo , Estudos Multicêntricos como Assunto , Distúrbios Nutricionais/metabolismo
5.
JAMA Pediatr ; 174(7): 649-656, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32338720

RESUMO

Importance: Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g). Objective: To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants. Design, Setting, and Participants: This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018. Interventions: Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT). Main Outcomes and Measures: Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power. Results: Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, -39; 95% CI, -45 to -32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, -0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of -4.5% (95% CI, -10.9 to 2.0). Morbidities did not differ between groups. Conclusions and Relevance: Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT01944696.


Assuntos
Bilirrubina/sangue , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Icterícia Neonatal/terapia , Fototerapia/métodos , Biomarcadores/sangue , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Icterícia Neonatal/sangue , Masculino , Estudos Retrospectivos
6.
J Perinatol ; 40(2): 180-193, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31420582

RESUMO

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.


Assuntos
Icterícia Neonatal/terapia , Fototerapia , História do Século XV , História do Século XVIII , História do Século XX , História do Século XXI , Humanos , Hiperbilirrubinemia Neonatal/história , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/terapia , Recém-Nascido de muito Baixo Peso , Icterícia Neonatal/história , Fototerapia/efeitos adversos , Fototerapia/instrumentação , Controle de Qualidade
7.
Pediatr Res ; 85(6): 865-873, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30710116

RESUMO

BACKGROUND: The action spectrum for bilirubin photodegradation has been intensively studied. However, questions still remain regarding which light wavelength most efficiently photodegrades bilirubin. In this study, we determined the in vitro effects of different irradiation wavelength ranges on bilirubin photodegradation. METHODS: In our in vitro method, normalized absolute irradiance levels of 4.2 × 1015 photons/cm2/s from light-emitting diodes (ranging from 390-530 nm) and 10-nm band-pass filters were used to irradiate bilirubin solutions (25 mg/dL in 4% human serum albumin). Bilirubin and its major photoisomer concentrations were determined; the half-life time of bilirubin (t1/2) was calculated for each wavelength range, and the spectral characteristics for bilirubin photodegradation products were obtained for key wavelengths. RESULTS: The in vitro photodegradation of bilirubin at 37 °C decreased linearly as the wavelength was increased from 390 to 500 nm with t1/2 decreasing from 63 to 17 min, respectively. At 460 ± 10 nm, a significantly lower rate of photodegradation and thus higher t1/2 (31 min) than that at 500 nm (17 min) was demonstrated. CONCLUSION: In our system, the optimum bilirubin photodegradation and lumirubin production rates occurred between 490 and 500 nm. Spectra shapes were remarkably similar, suggesting that lumirubin production was the major process of bilirubin photodegradation.


Assuntos
Bilirrubina/efeitos da radiação , Luz , Bilirrubina/análogos & derivados , Bilirrubina/sangue , Bilirrubina/química , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/terapia , Técnicas In Vitro , Recém-Nascido , Isomerismo , Fotólise/efeitos da radiação , Fototerapia/métodos , Albumina Sérica Humana/química , Albumina Sérica Humana/efeitos da radiação , Espectrofotometria
8.
Placenta ; 75: 1-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30712660

RESUMO

INTRODUCTION: Statins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency. METHODS: At E14.5, untreated pregnant wild-type (WT, n=13-18), untreated HO-1+/- (Het, n=6-9), and Het mice treated with pravastatin (Het+Pravastatin, n=12-14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas. RESULTS: Compared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0-73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2-5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas. DISCUSSION: Pravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.


Assuntos
Heme Oxigenase-1/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Proteínas de Membrana/metabolismo , Placentação/efeitos dos fármacos , Pravastatina/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Camundongos , Pravastatina/farmacologia , Gravidez , Distribuição Aleatória
9.
Lancet Glob Health ; 6(10): e1122-e1131, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30170894

RESUMO

BACKGROUND: Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia. METHODS: We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 µmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%. FINDINGS: Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 µW/cm2/nm (IQR 21·4-56·4) in the FSPT group and 50·4 µW/cm2/nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates. INTERPRETATION: FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants. FUNDING: Thrasher Research Fund and National Center for Advancing Translational Sciences.


Assuntos
Hiperbilirrubinemia Neonatal/terapia , Fototerapia/métodos , Eletricidade , Feminino , Humanos , Recém-Nascido , Masculino , Fototerapia/efeitos adversos , Estudos Prospectivos , Índice de Gravidade de Doença , Luz Solar , Resultado do Tratamento
10.
J Perinatol ; 38(11): 1532-1535, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30120424

RESUMO

OBJECTIVES: Transcutaneous bilirubin measurements (TcBs) provide a noninvasive method for screening infants for hyperbilirubinemia and have been used extensively in term and late preterm newborns in well baby nurseries, offices, and outpatient clinics. Several studies have also demonstrated the utility of TcBs as a screening tool for infants > 28 weeks' gestation and their ability to reduce the need for blood sampling. The objectives of this study are to identify how often TcBs are used among California Newborn Intensive Care Units (NICUs) in preterm, late preterm and term infants, and other aspects of jaundice management. METHODS: We conducted a survey on TcB use and practices relating to jaundice management in 150 California NICUs between April and October 2016. RESULTS: TcB screening is routinely used in 28% (42/150) of NICUs. Only 7% (11/150) of NICUs use TcB in preterm infants < 28 weeks. Practice varied similarly across NICU levels of care. Among the subset of NICUs that responded to questions related to phototherapy and screening practices, prophylactic phototherapy was used in 38% (23/59) and 90% (55/61) screened for glucose-6-phosphate dehydrogenase deficiency based on race, ethnicity, and/or family history. CONCLUSION(S): Despite studies validating the accuracy of TcB in preterm infants > 28 weeks, only 28% of California NICUs routinely use TcB devices. TcB screening in infants < 28 weeks gestation is not widely used and no recommendation can be made in this regard until there is more experience with its application using a standardized protocol in these infants and on a large scale.


Assuntos
Bilirrubina/análise , Recém-Nascido Prematuro , Icterícia Neonatal/diagnóstico , Triagem Neonatal/instrumentação , Bilirrubina/sangue , California , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Icterícia Neonatal/terapia , Triagem Neonatal/métodos , Fototerapia/efeitos adversos , Fatores de Tempo
11.
Pediatr Res ; 84(4): 494-498, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29967530

RESUMO

BACKGROUND: Bilirubin-induced neurologic dysfunction (BIND) is a spectrum of preventable neurological sequelae in jaundiced newborns. Current total plasma bilirubin (BT) concentration thresholds for phototherapy and/or exchange transfusion poorly predict BIND. METHODS: The unbound (free) bilirubin (Bf) measured at these BT thresholds provides additional information about the risk for BIND. Bf can be readily adapted to clinical use by determining Bf population parameters at current BT thresholds. These parameters can be established using a plasma bilirubin binding panel (BBP) consisting of BT, Bf, and two empiric constants, the maximum BT (BTmax) and the corresponding equilibrium association bilirubin constant (K). RESULTS: BTmax and K provide the variables needed to accurately estimate Bf at BT < BTmax to obtain Bf at threshold BT in patient samples. Once Bf population parameters are known, the BBP in a newborn can be used to identify poor bilirubin binding (higher Bf at the threshold BT compared with the population) and increased risk of BIND. CONCLUSION: The BBP can also be used in jaundice screening to better identify the actual BT at which intervention would be prudent. The BBP is used with current BT thresholds to better identify the risk of BIND and whether and when to intervene.


Assuntos
Bilirrubina/sangue , Doenças do Recém-Nascido/diagnóstico , Icterícia Neonatal/sangue , Icterícia Neonatal/terapia , Fototerapia/métodos , Albuminas/química , Bilirrubina/química , Sítios de Ligação , Fluorometria , Humanos , Recém-Nascido , Cinética , Programas de Rastreamento/métodos , Modelos Teóricos , Triagem Neonatal/métodos , Ligação Proteica , Medição de Risco
12.
Acta Paediatr ; 107(8): 1350-1356, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29532503

RESUMO

AIM: To identify neonates at risk of haemolytic hyperbilirubinaemia through near-concurrent measurements of total serum/plasma bilirubin (TB) or transcutaneous bilirubin (TcB) and end-tidal breath carbon monoxide (CO), corrected for ambient CO (ETCOc), an index of bilirubin production and haemolysis. METHODS: Paired TB/TcB (mg/dL) and ETCOc (ppm) measurements were obtained in newborns (n = 283) at 20 to <60 hours of age in five nurseries. TB/TcB values were assigned TB/TcB percentile risk values using the Bhutani hour-specific nomogram. In infants having two serial TB/TcB measurements (n = 76), TB rate of rise (ROR, mg/dL/h) was calculated. RESULTS: For the entire cohort (n = 283), 67.1% and 32.9% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.79 ± 1.84 vs 9.14 ± 2.25 mg/dL) and ETCOc (1.61 ± 0.45 vs 2.02 ± 1.35 ppm, p = 0.0002) were different between the groups. About 36.6% of infants with TB/TcB ≥75th percentile had ETCOc ≥ 2.0 ppm. In the subcohort of infants with serial TB/TcB measurements (n = 76), 44.7% and 55.3% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.28 ± 1.97 vs 9.53 ± 2.78 mg/dL), ETCOc (1.72 ± 0.48 vs 2.38 ± 1.89 ppm, p = 0.05) and TB ROR (0.011 ± 0.440 vs 0.172 ± 0.471 mg/dL/h) were different between the groups. CONCLUSION: The combined use of TB/TcB percentile risk assessments and ETCOc measurements can identify infants with haemolytic hyperbilirubinaemia. The addition of TB ROR can identify those infants with elimination disorders.


Assuntos
Bilirrubina/sangue , Monóxido de Carbono/análise , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Triagem Neonatal/métodos , Fototerapia/métodos , Análise de Variância , Estudos de Coortes , Feminino , Idade Gestacional , Hemólise/fisiologia , Humanos , Recém-Nascido , Masculino , Berçários para Lactentes , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Volume de Ventilação Pulmonar , Resultado do Tratamento
13.
Clin Perinatol ; 43(2): 215-32, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27235203

RESUMO

Preterm neonates with increased bilirubin production loads are more likely to sustain adverse outcomes due to either neurotoxicity or overtreatment with phototherapy and/or exchange transfusion. Clinicians should rely on expert consensus opinions to guide timely and effective interventions until there is better evidence to refine bilirubin-induced neurologic dysfunction or benefits of bilirubin. In this article, we review the evolving evidence for bilirubin-induced brain injury in preterm infants and highlight the clinical approaches that minimize the risk of bilirubin neurotoxicity.


Assuntos
Hiperbilirrubinemia Neonatal/prevenção & controle , Kernicterus/prevenção & controle , Fototerapia/métodos , Idade Gestacional , Humanos , Hiperbilirrubinemia Neonatal/complicações , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Recém-Nascido Prematuro , Kernicterus/etiologia , Medição de Risco , Fatores de Tempo
14.
Clin Perinatol ; 43(2): 291-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27235208

RESUMO

Phototherapy has been used to treat newborns with jaundice for more than 50 years with the presumption that it is safe and effective for all infants. In fact, this presumption may not be true for all infants, especially the smallest and most immature. The safety and efficacy of phototherapy have never really been questioned or adequately tested in the latter, yet clinical applications of phototherapy have been further refined as its mechanisms of action have been better understood and alternative light sources have become available. This article addresses what is known about the possible risks of photo-oxidative injury in extremely low birth weight infants.


Assuntos
Hematócrito , Hiperbilirrubinemia Neonatal/terapia , Icterícia Neonatal/terapia , Estresse Oxidativo , Fototerapia/efeitos adversos , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro
16.
Pediatr Res ; 79(3): 387-90, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26571225

RESUMO

BACKGROUND: Phototherapy using light in the spectral range of 410-500 nm, which overlaps the absorption of bilirubin, is the common treatment for neonatal hyperbilirubinemia. Hemoglobin (Hb) absorbs light strongly throughout this same range and thus can compete with bilirubin for this light and consequently reduce the efficacy of phototherapy. Here, we determined the effect of hematocrit (Hct) on in vitro bilirubin photoalteration using narrow-band blue (450 nm) light-emitting diodes (LEDs). METHODS: Suspensions with Hcts from 0 to 80% and 16 ± 1 mg/dl bilirubin were prepared by mixing red blood cells (RBCs), bilirubin (30 mg/dl) in 4% human serum albumin, and normal saline. Aliquots of each suspension were exposed to blue light at equal irradiances. Before and after 60 min of exposure, bilirubin levels in supernatants (n = 46) were measured using a diazo-dye method. RESULTS: Bilirubin photoalteration steeply decreased by ~60% as Hct increased from 0 to 10%. Over the clinically relevant range of 30-70% Hct, the decrease was significant, but less drastic, exhibiting a quasi-linear dependence on Hct. CONCLUSION: Bilirubin photoalteration under blue light in vitro is significantly reduced as Hct increases. Clinical studies are warranted to confirm these in vitro observations that Hct can affect the efficacy of phototherapy.


Assuntos
Bilirrubina/sangue , Hematócrito , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/terapia , Luz , Fototerapia/métodos , Adulto , Bilirrubina/química , Contagem de Eritrócitos , Eritrócitos/citologia , Humanos , Albumina Sérica/química
17.
N Engl J Med ; 373(12): 1115-24, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26376136

RESUMO

BACKGROUND: Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown. METHODS: We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn. RESULTS: We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 µW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0°C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion. CONCLUSIONS: Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810.).


Assuntos
População Negra , Helioterapia , Hiperbilirrubinemia Neonatal/terapia , Sistema ABO de Grupos Sanguíneos , Bilirrubina/sangue , Feminino , Idade Gestacional , Helioterapia/efeitos adversos , Helioterapia/métodos , Humanos , Recém-Nascido , Masculino , Nigéria , Resultado do Tratamento
18.
Pediatr Res ; 77(2): 334-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25420178

RESUMO

BACKGROUND: Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors. METHODS: We utilized a novel modification of a previously developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubin-induced neurotoxicity. RESULTS: TB and BBC levels ranged from 0.7-22.8 to 6.3-47.5 mg/dl, respectively. Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002) with a slope of 0.93 mg/dl/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45 and 67% saturation of our observed regression line, respectively. CONCLUSION: We speculate that the spread of BBC levels around the regression line (± 5.8 mg/dl) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared with TB and GA.


Assuntos
Bilirrubina/metabolismo , Bilirrubina/toxicidade , Recém-Nascido Prematuro/metabolismo , Síndromes Neurotóxicas/sangue , Síndromes Neurotóxicas/etiologia , Medição de Risco/métodos , Análise de Variância , Bilirrubina/sangue , Fluorometria/métodos , Idade Gestacional , Humanos , Recém-Nascido , Modelos Logísticos , Estudos Prospectivos , Ligação Proteica
19.
Neuroimage Clin ; 5: 169-77, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25068107

RESUMO

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.


Assuntos
Encéfalo/patologia , Recém-Nascido de muito Baixo Peso/fisiologia , Encéfalo/crescimento & desenvolvimento , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Masculino
20.
Pediatrics ; 133(6): e1568-74, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24864170

RESUMO

OBJECTIVES: Evaluate safety and efficacy of filtered-sunlight phototherapy (FS-PT). METHODS: Term/late preterm infants #14 days old with clinically significant jaundice, assessed by total bilirubin (TB) levels, were recruited from a maternity hospital in Lagos, Nigeria. Sunlight was filtered with commercial window-tinting films that remove most UV and significant levels of infrared light and transmit effective levels of therapeutic blue light. After placing infants under an FS-PT canopy, hourly measurements of axillary temperatures, monitoring for sunburn, dehydration, and irradiances of filtered sunlight were performed. Treatment was deemed safe and efficacious if infants were able to stay in FS-PT for $5 hours and rate of rise of TB was ,0.2 mg/dL/h for infants #72 hours of age or TB decreased for infants .72 hours of age. RESULTS: A total of 227 infants received 258 days of FS-PT. No infant developed sunburn or dehydration. On 85 (33%) of 258 treatment days, infants were removed briefly from FS-PT due to minor temperature-related adverse events. No infant met study exit criteria. FS-PT was efficacious in 92% (181/197) of evaluable treatment days. Mean 6 SD TB change was ­0.06 6 0.19 mg/dL/h. The mean 6 SD (range) irradiance of FS-PT was 38 6 22 (2­115) mW/cm2/nm, measured by the BiliBlanket Meter II. CONCLUSIONS: With appropriate monitoring, filtered sunlight is a novel, practical, and inexpensive method of PT that potentially offers safe and efficacious treatment strategy for management of neonatal jaundice in tropical countries where conventional PT treatment is not available.


Assuntos
Negro ou Afro-Americano , Países em Desenvolvimento , Helioterapia/métodos , Doenças do Prematuro/terapia , Icterícia Neonatal/terapia , Bilirrubina/sangue , Temperatura Corporal , Feminino , Filtração , Helioterapia/efeitos adversos , Maternidades , Humanos , Recém-Nascido , Icterícia Neonatal/sangue , Masculino , Nigéria , Resultado do Tratamento
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