Sunlight for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates.

BACKGROUND: Acute bilirubin encephalopathy (ABE) and the other serious complications of severe hyperbilirubinemia in the neonate occur far more frequently in low- and middle-income countries (LMIC). This is due to several factors that place babies in LMIC at greater risk for hyperbilirubinemia, including increased prevalence of hematologic disorders leading to hemolysis, increased sepsis, less prenatal or postnatal care, and a lack of resources to treat jaundiced babies. Hospitals and clinics face frequent shortages of functioning phototherapy machines and inconsistent access to electricity to run the machines. Sunlight has the potential to treat hyperbilirubinemia: it contains the wavelengths of light that are produced by phototherapy machines. However, it contains harmful ultraviolet light and infrared radiation, and prolonged exposure has the potential to lead to sunburn, skin damage, and hyperthermia or hypothermia. OBJECTIVES: To evaluate the efficacy of sunlight administered alone or with filtering or amplifying devices for the prevention and treatment of clinical jaundice or laboratory-diagnosed hyperbilirubinemia in term and late preterm neonates. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 5), MEDLINE, Embase, and CINAHL on 2 May 2019. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster RCTs. We updated the searches on 1 June 2020. SELECTION CRITERIA: We included RCTs, quasi-RCTs, and cluster RCTs. We excluded crossover RCTs. Included studies must have evaluated sunlight (with or without filters or amplification) for the prevention and treatment of hyperbilirubinemia or jaundice in term or late preterm neonates. Neonates must have been enrolled in the study by one-week postnatal age. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were: use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, chronic bilirubin encephalopathy, and death. MAIN RESULTS: We included three RCTs (1103 infants). All three studies had small sample sizes, were unblinded, and were at high risk of bias. We planned to undertake four comparisons, but only found studies reporting on two. Sunlight with or without filters or amplification compared to no treatment for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates One study of twice-daily sunlight exposure (30 to 60 minutes) compared to no treatment reported the incidence of jaundice may be reduced (risk ratio [RR] 0.61, 95% confidence interval [CI] 0.45 to 0.82; risk difference [RD] -0.14, 95% CI -0.22 to -0.06; number needed to treat for an additional beneficial outcome [NNTB] 7, 95% CI 5 to 17; 1 study, 482 infants; very low-certainty evidence) and the number of days that an infant was jaundiced may be reduced (mean difference [MD] -2.20 days, 95% CI -2.60 to -1.80; 1 study, 482 infants; very low-certainty evidence). There were no data on safety or potential harmful effects of the intervention. The study did not assess use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, and long-term consequences of hyperbilirubinemia. The study showed that sunlight therapy may reduce rehospitalization rates within seven days of discharge for treatment for hyperbilirubinemia, but the evidence was very uncertain (RR 0.55, 95% CI 0.27 to 1.11; RD -0.04, -0.08 to 0.01; 1 study, 482 infants; very low-certainty evidence). Sunlight with or without filters or amplification compared to other sources of phototherapy for the treatment of hyperbilirubinemia in infants with confirmed hyperbilirubinemia Two studies (621 infants) compared the effect of filtered-sunlight exposure to other sources of phototherapy in infants with confirmed hyperbilirubinemia. Filtered-sunlight phototherapy (FSPT) and conventional or intensive electric phototherapy led to a similar number of days of effective treatment (broadly defined as a minimal increase of total serum bilirubin in infants less than 72 hours old and a decrease in total serum bilirubin in infants more than 72 hours old on any day that at least four to five hours of sunlight therapy was available). There may be little or no difference in treatment failure requiring exchange transfusion (typical RR 1.00, 95% CI 0.06 to 15.73; typical RD 0.00, 95% CI -0.01 to 0.01; 2 studies, 621 infants; low-certainty evidence). One study reported ABE, and no infants developed this outcome (RR not estimable; RD 0.00, 95% CI -0.02 to 0.02; 1 study, 174 infants; low-certainty evidence). One study reported death as a reason for study withdrawal; no infants were withdrawn due to death (RR not estimable; typical RD 0.00, 95% CI -0.01 to 0.01; 1 study, 447 infants; low-certainty evidence). Neither study assessed long-term outcomes. Possible harms: both studies showed a probable increased risk for hyperthermia (body temperature greater than 37.5 °C) with FSPT (typical RR 4.39, 95% CI 2.98 to 6.47; typical RD 0.30, 95% CI 0.23 to 0.36; number needed to treat for an additional harmful outcome [NNTH] 3, 95% CI 2 to 4; 2 studies, 621 infants; moderate-certainty evidence). There was probably no difference in hypothermia (body temperature less than 35.5 °C) (typical RR 1.06, 95% CI 0.55 to 2.03; typical RD 0.00, 95% CI -0.03 to 0.04; 2 studies, 621 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Sunlight may be an effective adjunct to conventional phototherapy in LMIC settings, may allow for rotational use of limited phototherapy machines, and may be preferable to families as it can allow for increased bonding. Filtration of sunlight to block harmful ultraviolet light and frequent temperature checks for babies under sunlight may be warranted for safety. Sunlight may be effective in preventing hyperbilirubinemia in some cases, but these studies have not demonstrated that sunlight alone is effective for the treatment of hyperbilirubinemia given its sporadic availability and the low or very low certainty of the evidence in these studies.

Risk of Neonatal Short-Term Adverse Outcomes Associated with Noninfectious Intrapartum Hyperthermia: A Nested Case-Control Retrospective Study.

OBJECTIVE: This study aimed to identify risk factors for adverse neonatal outcomes in neonates born to mothers with noninfectious intrapartum hyperthermia. STUDY DESIGN: A retrospective study was conducted of 460 singleton deliveries diagnosed with noninfectious intrapartum hyperthermia. Logistic regression was used to estimate the association between ante- and intrapartum risk factors and neonatal outcomes. RESULTS: The 460 singleton pregnant women were 19 to 43 years of age. They developed an intrapartum temperature of ≥37.5°C somewhere between 340/7 to 414/7 weeks' gestation; 437 (95%) were nulliparous. Meconium-stained amniotic fluid was associated with positive pressure ventilation or intubation ventilation (odds ratio [OR] = 5.940, 95% confidence interval [CI]: 2.038-17.318), birth depression (OR = 6.288, 95% CI: 2.273-17.399), and wet lung (OR = 2.747, 95% CI: 1.322-5.709). Induction of labor with artificial rupture of membranes (AROM; OR = 2.632, 95% CI: 1.325-5.228) was associated with neonatal infections. Maternal temperature ≥ 38°C was associated with neonate's artery blood gas pH < 7.3 (OR = 2.366, 95%CI: 1.067-5.246) and wet lung (OR = 2.909, 95% CI: 1.515-5.586). Maternal elevated C-reactive protein (CRP) was associated with neonatal infections (OR = 1.993, 95% CI: 1.260-3.154) and wet lung (OR = 2.600, 95% CI: 1.306-5.178). CONCLUSION: Meconium-stained amniotic fluid, induction of labor, maternal temperature ≥ 38°C, and elevated CRP during labor were risk factors for adverse neonatal outcomes.

Normothermia in Patients With Sepsis Who Present to Emergency Departments Is Associated With Low Compliance With Sepsis Bundles and Increased In-Hospital Mortality Rate.

OBJECTIVES: To investigate the impact of normothermia on compliance with sepsis bundles and in-hospital mortality in patients with sepsis who present to emergency departments. DESIGN: Retrospective multicenter observational study. PATIENTS: Nineteen university-affiliated hospitals of the Korean Sepsis Alliance participated in this study. Data were collected regarding patients who visited emergency departments for sepsis during the 1-month period. The patients were divided into three groups based on their body temperature at the time of triage in the emergency department (i.e., hypothermia [< 36°C] vs normothermia [36-38°C] vs hyperthermia [> 38°C]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 64,021 patients who visited emergency departments, 689 with community-acquired sepsis were analyzed (182 hyperthermic, 420 normothermic, and 87 hypothermic patients). The rate of compliance with the total hour-1 bundle was lowest in the normothermia group (6.0% vs 9.3% in hyperthermia vs 13.8% in hypothermia group; p = 0.032), the rate for lactate measurement was lowest in the normothermia group (62.1% vs 73.1% vs 75.9%; p = 0.005), and the blood culture rate was significantly lower in the normothermia than in the hyperthermia group (p < 0.001). The in-hospital mortality rates in the hyperthermia, normothermia, and hypothermia groups were 8.5%, 20.6%, and 30.8%, respectively (p < 0.001), but there was no significant association between compliance with sepsis bundles and in-hospital mortality. However, in a multivariate analysis, compared with hyperthermia, normothermia was significantly associated with an increased in-hospital mortality (odds ratio, 2.472; 95% CI, 1.005-6.080). This association remained significant even after stratifying patients by median lactate level. CONCLUSIONS: Normothermia at emergency department triage was significantly associated with an increased risk of in-hospital mortality and a lower rate of compliance with the sepsis bundle. Despite several limitations, our findings suggest a need for new strategies to improve sepsis outcomes in this group of patients.

Pavement Burns Treated at a Desert Burn Center: Analysis of Mechanisms and Outcomes.

Burns from contact with hot pavement are a common mechanism treated at burn centers located in desert climates. Previous work has shown increased risk of pavement burns as ambient temperatures rise above 95 degrees. In direct sunlight, pavement absorbs radiant energy causing the temperature to rise high enough to cause second-degree burns in seconds. The goal of this study is to review the mechanisms and outcomes of patients suffering pavement burns and to compare patients who presented with hyperthermia to their normothermia counterparts. A retrospective chart review was performed on pavement burns at an ABA-verified Burn Center for 5 years from 2014 to 2018. A total of 195 patients were identified. It was found that 50.5% of admitted pavement burn patients required burn excision and 35.9% required split-thickness skin grafting. The leading causes of pavement burn admissions were found down by EMS and walking on pavement at 21.6% each, followed by mechanical falls at 15.1%. We found that patients with recorded hyperthermia had statistically significant increase in 30-day hospital mortality, intensive care unit days, surgical procedures, and %TBSA. Data provided from this study can be used for a public health initiative to help patients who may be at risk of acquiring pavement burns. The data may also be helpful for clinicians gaining information about the management, mechanism, and outcomes of pavement burn patients.

Drug-associated hyperthermia: A longitudinal analysis of hospital presentations.

WHAT IS KNOWN AND OBJECTIVE: Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs can affect thermoregulation through mechanisms including altering the neurotransmitters that cause increased heat production or decreased heat loss and may, therefore, be associated with hyperthermia. This study aimed to examine hospitalizations and emergency department (ED) presentations due to hyperthermia and to investigate the potential association with drug therapy. METHODS: A retrospective analysis of ED presentations and hospitalizations due to hyperthermia in all four major hospitals in Tasmania, Australia, between July 2010 and December 2018 was performed. Data of patients aged ≥18 years were extracted from the hospital digital medical records and analysed for the prevalence, trends and various potential risk factors for hyperthermia, such as age, environmental temperature and drug therapy. RESULTS: This study included 224 patients. The data illustrated a trend with time, albeit not statistically significant, towards increasing hospital presentations due to hyperthermia. Antiepileptics (P = .03) and furosemide (P = .04) were the most frequently used drugs in patients with primary hyperthermia. The high use of levothyroxine in the study population (6.7%) stood out compared with the estimated national average (2.1%). Various drug classes associated with hyperthermia were used significantly more in the age group ≥60 years, suggesting polypharmacy in the elderly as a contributing factor for hyperthermia. WHAT IS NEW AND CONCLUSION: This study reports a possible association of some drugs, particularly diuretics (furosemide), antiepileptics and levothyroxine, with hyperthermia. Healthcare professionals should be aware of the increasing prevalence of hyperthermia and the possible involvement of drugs.