Review question
In jaundiced newborn infants, is intermittent phototherapy compared with continuous phototherapy effective in reducing bilirubin levels.
Background
Neonatal jaundice is a yellowish discolouration of the of the newborn infant's skin due to high bilirubin (a yellow compound that occurs naturally in the blood) levels. Phototherapy (light therapy) is widely accepted as an effective treatment for jaundiced newborn infants. Phototherapy is usually used continuously but intermittent phototherapy has some potential advantages such as improved maternal feeding and bonding. We do not know if intermittent phototherapy is as effective as continuous phototherapy.
Study characteristics
We found 33 studies that assessed the effect of intermittent phototherapy in infants through searches of medical databases up to January 2022. Of these, 12 studies (involving a total of 1600 infants) were eligible for inclusion in this review. One study is currently ongoing and four are awaiting classification. Our primary outcomes of interest were the rate of fall in the serum bilirubin levels and bilirubin-induced brain dysfunction (BIND). Search is up-to-date as of 31 January 2022.
Key results
We found little or no difference between intermittent phototherapy and continuous phototherapy in reducing bilirubin levels. Continuous phototherapy was more effective in preterm infants, however, we do not know if this is a meaningful difference. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed.
Certainty of evidence
Overall, we rated the certainty of evidence as low or very low. Large, high-quality trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. Continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. Large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.
To assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.
Searches were conducted on 31 January 2022 in the following databases: CENTRAL via CRS Web, MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.
We included RCTs, cluster-RCTs and quasi-RCTs comparing intermittent phototherapy with continuous phototherapy in jaundiced infants (both term and preterm) up to the age of 30 days. We compared intermittent phototherapy with continuous phototherapy by any method and at any dose and duration as defined by the authors.
Three review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Our primary outcomes of interest were rate of decline of serum bilirubin, and kernicterus. We used the GRADE approach to assess the certainty of evidence.
We included 12 RCTs (1600 infants) in the review. There is one ongoing study and four awaiting classification. There was little or no difference between intermittent phototherapy and continuous phototherapy with respect to rate of decline of bilirubin in jaundiced newborn infants (MD -0.09 micromol/L/hr, 95% CI -0.21 to 0.03; I² = 61%; 10 studies; 1225 infants; low-certainty evidence). One study involving 60 infants reported no incidence of bilirubin induced brain dysfunction (BIND). It is uncertain whether either intermittent or continuous phototherapy reduces BIND because the certainty of this evidence is very low. There was little or no difference in treatment failure (RD 0.03, 95% CI 0.08 to 0.15; RR 1.63, 95% CI 0.29 to 9.17; 1 study; 75 infants; very low-certainty evidence) or infant mortality (RD -0.01, 95% CI -0.03 to 0.01; RR 0.69, 95% CI 0.37 to 1.31 I² = 0%; 10 studies, 1470 infants; low-certainty evidence).