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

Abstract

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.

1

PRISMA study flow diagram.

2

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.

3

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

1.1. Analysis

Comparison 1: Low‐risk term and late preterm infants (based on risk criteria defined by Bhutani 1999), Outcome 1: Rate of rehospitalization

1.2. Analysis

Comparison 1: Low‐risk term and late preterm infants (based on risk criteria defined by Bhutani 1999), Outcome 2: Incidence of jaundice

1.3. Analysis

Comparison 1: Low‐risk term and late preterm infants (based on risk criteria defined by Bhutani 1999), Outcome 3: Duration of jaundice (days)

2.1. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 1: Treatment failure requiring exchange transfusion

2.2. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 2: Acute bilirubin encephalopathy

2.3. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 3: Death

2.4. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 4: Rate of change of serum bilirubin (μmol/L/hour)

2.5. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 5: Sunburn

2.6. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 6: Hyperthermia (> 38 °C)

2.7. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 7: Proportion of days of effective treatment

2.8. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 8: Hypothermia (< 35.5 °C)

2.9. Analysis

Comparison 2: Infants with confirmed hyperbilirubinemia, Outcome 9: Dehydration