Fototerapia domiciliaria versus hospitalaria para el tratamiento de la ictericia no hemolítica en lactantes de más de 37 semanas de gestación
Resumen
Antecedentes
La fototerapia habitualmente se utiliza para el tratamiento de la ictericia neonatal, y actualmente en ciertos centros se utiliza la fototerapia domiciliaria. La fototerapia domiciliaria ofrece posibles ventajas al evitar los ingresos hospitalarios prolongados, promover el vínculo entre la madre y el lactante y reducir los costos de hospitalización. Los problemas potenciales incluyen una mayor duración de la fototerapia, un aumento de los reingresos hospitalarios y un aumento de la encefalopatía por bilirrubina.
Objetivos
Comparar la fototerapia domiciliaria exclusivamente versus la fototerapia hospitalaria exclusivamente o una combinación de fototerapia domiciliaria y fototerapia hospitalaria para el tratamiento de la ictericia no hemolítica en lactantes a término de hasta 28 días de vida. Se planificó incluir subgrupos específicos según la duración de la estancia hospitalaria, el método de fototerapia y los criterios de listo para el alta.
Métodos de búsqueda
Se hicieron búsquedas en el registro especializado del Grupo Cochrane de Neonatología (Cochrane Neonatal Review Group), Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL) enero de 2013, número 1, parte de The Cochrane Library, MEDLINE (desde 1966 hasta el 15 de febrero de 2013), CINAHL (desde 1982 hasta el 15 febrero de 2013) y en EMBASE (desde 1988 hasta el 15 febrero de 2013). Se hicieron búsquedas de resúmenes de los Pediatric Academic Societies' Annual Meetings de 2000 a 2013. Se hicieron búsquedas de ensayos en curso en los siguientes sitios web: ClinicalTrials.gov (http://clinicaltrials.gov/) y Current Controlled Trials (http://controlled‐trials.com/).
Criterios de selección
Estudios aleatorios y cuasialeatorios que compararon lactantes a término que recibieron fototerapia domiciliaria exclusivamente versus fototerapia hospitalaria exclusivamente o una combinación de las dos para la ictericia no hemolítica.
Obtención y análisis de los datos
Dos autores de la revisión de forma independiente evaluaron la calidad de los ensayos y extrajeron los datos.
Resultados principales
No se identificaron estudios que cumplieran los criterios de inclusión predefinidos.
Conclusiones de los autores
Actualmente no están disponibles pruebas de alta calidad para apoyar o refutar la práctica de la fototerapia domiciliaria para la ictericia no hemolítica en los lactantes de más de 37 semanas de gestación.
PICO
Resumen en términos sencillos
Fototerapia domiciliaria versus hospitalaria para el tratamiento de la ictericia neonatal sin complicaciones en neonatos a término
Los neonatos desarrollan habitualmente una afección llamada ictericia. La ictericia ocurre como resultado de la acumulación de un pigmento amarillo‐anaranjado llamado bilirrubina en la piel y los ojos. La bilirrubina en mayores concentraciones puede dañar el cerebro y puede tener efectos perjudiciales graves a largo plazo. La fototerapia es una forma de tratamiento utilizada en los neonatos para reducir los niveles de bilirrubina. "La fototerapia domiciliaria" se puede utilizar en el contexto domiciliario con supervisión apropiada. La fototerapia domiciliaria se utiliza solamente en los casos de ictericia neonatal sin complicaciones. La fototerapia domiciliaria puede ofrecer ciertas ventajas como reducción en los costos hospitalarios y mejores vínculos entre el lactante y madre. Por otro lado, la fototerapia domiciliaria se podría asociar con problemas como mayor riesgo de efectos perjudiciales de la bilirrubina sobre el cerebro y un aumento del riesgo de reingreso hospitalario. En esta revisión Cochrane, la fototerapia domiciliaria se comparó con la fototerapia hospitalaria para la ictericia sin complicaciones en neonatos a término. Los autores de la revisión no encontraron estudios que cumplieran los criterios de elegibilidad. Los autores de esta revisión Cochrane concluyen que actualmente no hay pruebas de alta calidad disponibles para apoyar o refutar el uso de la fototerapia domiciliaria para la ictericia neonatal sin complicaciones.
Authors' conclusions
Background
Description of the condition
Jaundice is a common condition in neonates, occurring in 60% to 84% of late term and term infants (Keren 2009; Kliegman 2011; Bhutani 2011). Jaundice refers to a yellow discolouration of the skin and sclera that occurs when levels of bilirubin are increased. Bilirubin is produced by the catabolism of haemoglobin. Haeme is broken down in the reticuloendothelial system to biliverdin and carbon monoxide, and biliverdin is reduced to bilirubin by biliverdin reductase (Moerschel 2008). Bilirubin is conjugated by glucuronosyl transferase to bilirubin diglucuronide, which is water soluble and can be excreted easily by the liver and biliary tract (Moerschel 2008). If the rate of bilirubin production exceeds the rate of its elimination, the end result is an increase in total serum bilirubin—a clinical condition called hyperbilirubinaemia.
Distinctive aspects of normal newborn physiology predispose to hyperbilirubinaemia, including increased bilirubin synthesis, decreased binding and transport, impaired conjugation and excretion and enhanced enterohepatic circulation of bilirubin. Breast feeding may also contribute to benign neonatal hyperbilirubinaemia. Normal physiological levels of total serum bilirubin are controversial, as several factors affect these, such as gestational age, birthweight, disease state, degree of hydration, nutritional status and ethnicity. Benign neonatal hyperbilirubinaemia is also known as physiological jaundice. The causes of non‐physiological or pathological hyperbilirubinaemia are varied and include disorders of bilirubin production, disorders of bilirubin clearance, metabolic and endocrine disorders, increased enterohepatic circulation and substances affecting the binding of bilirubin to albumin.
Unconjugated bilirubin is lipid soluble and can easily cross the blood‐brain barrier. Unconjugated bilirubin is toxic to the central nervous system and in high concentrations can penetrate the brain cells, leading to neuronal dysfunction and death. Factors that determine the toxicity of bilirubin in neurons are complex and are not well understood (AAP 2004). Neurological damage can take the form of acute or chronic bilirubin encephalopathy. Acute bilirubin encephalopathy is an evolving encephalopathy that can progress in three phases. In the initial phase, the infant displays lethargy, hypotonia, reduced movement and a poor suck. The intermediate phase consists of cardinal signs of moderate stupor, irritability and increased tone; retrocollis and opisthotonus may be noted. The advanced stage is characterised by deep stupor, increased tone, inability to feed and a shrill cry; seizures may occur (AAP 2004). Chronic bilirubin encephalopathy (called kernicterus) is the term reserved for infants who have permanent sequelae (AAP 2004). Features of chronic bilirubin encephalopathy include athetoid cerebral palsy, high‐frequency sensorineural hearing loss, palsy of vertical gaze and dental enamel hypoplasia (AAP 2004).
Description of the intervention
Phototherapy causes structural changes in the bilirubin molecule and results in the formation of more polar stereoisomers, which are water soluble and can be excreted easily in the urine (Mreihil 2010). Phototherapy can be administered by a variety of different methods (e.g. conventional halogen lamps, fluorescent lamps, fibreoptic systems) (Kumar 2010). Phototherapy has traditionally been used in the hospital setting but can be provided in the home if appropriate equipment and support are available. Home phototherapy can be exclusively home‐based or can be preceded or followed by hospital phototherapy. This is a matter of importance because of the rising trend toward early discharges from hospital. Home phototherapy for uncomplicated physiological hyperbilirubinaemia has led to appropriate reductions in serum bilirubin (Tudehope 2000). Home phototherapy can be performed with conventional lamps or with the use of a fibreoptic system. Factors likely to be considered when a patient is recommended for home phototherapy include distance from hospital, motivation and competency of the parents. A Cochrane review looking at types of phototherapy has been completed. It looks at the effectiveness of fibreoptic compared with conventional phototherapy by assessing several different parameters and use of these treatments in different conditions (Mills 2009), Another Cochrane review compared light‐emitting diodes versus conventional light sources for providing phototherapy (Kumar 2011).
How the intervention might work
Neonatal jaundice may have to be treated with phototherapy to prevent the damaging effects of unconjugated hyperbilirubinaemia on the developing brain (Mreihil 2010). Guidelines for the treatment of neonatal jaundice vary worldwide (Hansen 2000). The American Academy of Pediatrics (AAP) clinical practice guidelines were put forth in 2004 with the aim of preventing and treating hyperbilirubinaemia in infants with a gestational age of 35 weeks or more (AAP 2004). Several factors may affect the dose and efficacy of phototherapy, such as spectrum of light emitted, spectral irradiance delivered to the surface of the infant, spectral power, the cause of jaundice and total serum bilirubin at the start of phototherapy (AAP 2004). The evidence base for the treatment of hyperbilirubinaemia in term infants, especially with regards to prevention of neurodevelopmental damage, is very limited; overall, four studies reported an absolute risk reduction rate of 10% to 17% for prevention of serum bilirubin levels greater than 20 mg/dL in healthy infants with jaundice when phototherapy was used (Ip 2004).
Home phototherapy may prevent prolonged hospitalisation. It can promote mother‐infant bonding and lead to increased parental satisfaction (Grabert 1986). Parents may experience a sense of independence and control regarding the care of their baby when using home phototherapy. Its use may result in a reduction in the costs of treatment. Home phototherapy may provide an opportunity to review the mother or the baby for other problems (aside from jaundice) in the early neonatal period, which may not have been obvious in the hospital setting. Three observational studies have looked at home versus hospital phototherapy in term infants. One of these studies revealed that the average reduction in serum bilirubin concentration was similar in the two groups after the first day of treatment. However, the duration of phototherapy was longer for the group treated at home (Slater 1984). The second study revealed that both mean daily reduction in serum bilirubin concentration and mean duration of treatment were significantly less for the home group as compared with the hospital group (Zainab 2003). The third study revealed that the two groups were comparable with regards to reduction in bilirubin levels and duration of phototherapy, and that home phototherapy was a feasible, safe and effective alternative to in‐hospital phototherapy for otherwise healthy, jaundiced infants with motivated and capable parents. This study also demonstrated a significant reduction in costs with home phototherapy (Eggert 1985).
Why it is important to do this review
Potential problems with home phototherapy include increased risk of bilirubin encephalopathy, increased duration of phototherapy and increased risk of readmission to hospital. Home phototherapy can be cheaper to perform than hospital‐based phototherapy, as it releases valuable bed space; however home phototherapy also has the potential for increased costs because of the required equipment and support personnel and the risk of readmission. Home phototherapy may facilitate establishment of the parent‐infant bond. We reviewed the literature to determine the risks and benefits of home versus hospital phototherapy for the treatment of non‐haemolytic jaundice in term infants.
Objectives
To compare exclusively home‐based versus exclusively hospital‐based phototherapy or a combination of home‐ and hospital‐based phototherapy for the management of non‐haemolytic jaundice in term infants up to 28 days of age. We planned to include specific subgroups for duration in hospital, method of phototherapy and criteria for readiness for discharge.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) or quasi‐RCTs in which individual newborns or clusters of infants were randomly assigned to receive phototherapy at home or in the hospital.
Types of participants
Newborn infants (gestation of 37 weeks or more at birth) up to 28 days of age with jaundice or an elevated serum bilirubin (as defined in individual studies) who required phototherapy for non‐haemolytic jaundice. Non‐haemolytic jaundice was defined by the absence of jaundice in the first 24 hours of life or the absence of progressive or prolonged jaundice, a negative Coombs' test and the absence of anaemia or an increased reticulocyte count. Infants otherwise were to be healthy and feeding well.
Types of interventions
Exclusively home‐based phototherapy versus exclusively hospital‐based phototherapy or combinations of hospital and home phototherapy (e.g. phototherapy commenced in the hospital and participant discharged home on phototherapy, or phototherapy commenced at home and participant transferred to hospital for continuation) for non‐haemolytic jaundice in term infants. We planned to consider any type of phototherapy device. We planned to consider for inclusion any trial in which phototherapy was undertaken in the home setting (even if initiated in hospital).
Types of outcome measures
Primary outcomes
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Rate of change of serum bilirubin (micromoles/L/h) from initiation of phototherapy to cessation of phototherapy.
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Duration of phototherapy from initiation to end (hours).
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Duration of time exposed to phototherapy (hours). Some infants will have short periods off phototherapy for feeding, etc.
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Incidence of acute bilirubin encephalopathy, which ranges from the initial phase of lethargy, hypotonia, reduced movement and a poor suck to the advanced phase of deep stupor, hypertonia, inability to feed and a shrill cry or seizures.
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Incidence (percentage) of chronic bilirubin encephalopathy or kernicterus, defined by a tetrad of choreoathetoid cerebral palsy, high‐frequency sensorineural hearing loss, palsy of vertical gaze and dental enamel hypoplasia.
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Rate of treatment failure (percentage) (defined as the need for exchange transfusion).
Secondary outcomes
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Need for recommencement of phototherapy after initial cessation for increased serum bilirubin.
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Rate of rehospitalisation within seven days of discharge for recommencement of phototherapy.
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Costs (however defined in individual studies).
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Parent‐infant bonding.
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Maternal satisfaction.
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Nursing satisfaction (as defined in individual studies).
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Co‐interventions (e.g. fluid supplementation, cessation of breast milk).
Search methods for identification of studies
Electronic searches
We used the standard search strategy for the Cochrane Neonatal Review Group. We searched the Cochrane Neonatal Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) January 2013, Issue 1, part of The Cochrane Library, MEDLINE (from 1966 to 15 February 2013), CINAHL (from 1982 to 15 February 2013) and EMBASE (from 1988 to 15 February 2013), using the following strategy.
Medical Subject Heading (MeSH) search terms "Jaundice" OR the text words "hyperbilirubin$"
AND
MeSH search term "Infant" OR the text words "neonat$", "infant", "term", "newborn"
AND
MeSH search term "Phototherapy" OR text words "biliblanket", "wallaby", "phototherapy", "fiber optic"
AND
MeSH search term "randomised controlled trial".
Searching other resources
We searched previous reviews (including cross‐references). Searches were not restricted to publications in the English language or to published data.
We searched for abstracts online from the Pediatric Academic Societies Annual Meetings (Abstract2view) from 2000 to 2013.
We searched for ongoing trials on the following websites: ClinicalTrials.gov (http://clinicaltrials.gov/) and Current Controlled Trials (http://controlled‐trials.com/).
Data collection and analysis
We used the standard methods of The Cochrane Collaboration and its Neonatal Review Group (Higgins 2011).
Selection of studies
Both review authors worked independently to search for trials for inclusion.
Data extraction and management
Both review authors extracted data independently and, when required, resolved differences by discussion. It was planned to contact study investigators to ask for additional information or data if required, once missing data had been identified.
Assessment of risk of bias in included studies
Both review authors worked independently to assess trials for methodological quality. Studies were assessed using the following key criteria: allocation concealment (blinding of randomisation), blinding of intervention, completeness of follow‐up and blinding of outcome measurement, with a rating assigned as follows: low risk—adequate (any truly random process, e.g. random number table; computer random number generator); high risk—inadequate (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number); unclear risk—no or unclear information provided (Higgins 2002).
In addition, we planned to evaluate the following issues and enter the findings into the risk of bias table.
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Sequence generation: Was the allocation sequence adequately generated?
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Allocation concealment: Was allocation adequately concealed?
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Blinding of participants, personnel and outcome assessors: Was knowledge of the allocated intervention adequately prevented during the study? At study entry? At the time of outcome assessment? Although it is impossible to completely blind participants (parents) or health professionals to the nature of the intervention, outcome assessors can be blinded.
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Incomplete outcome data: Were incomplete outcome data adequately addressed?
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Selective outcome reporting: Are reports of the study free of the suggestion of selective outcome reporting?
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Other sources of bias: Was the study apparently free of other problems that could put it at high risk of bias?
Measures of treatment effect
We planned to perform statistical analyses using Review Manager software (RevMan 2011). We planned to analyse categorical data using risk ratio (RR), risk difference (RD), the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH). We planned to analyse continuous data using weighted mean difference (WMD). We planned to report the 95% confidence interval (CI) for all estimates.
Unit of analysis issues
We planned to include in the review cluster‐randomised trials. We planned to confirm that the order of treatments had been randomly assigned (Higgins 2002). We planned to attempt to access paired and unpaired data (Higgins 2002). We planned to impute the correlation coefficient from data provided in the included studies in this meta‐analysis. If this information was not available, we planned to assume a value of 0.4 and conduct a sensitivity analysis by successively using r = 0.3 and r = 0.5.
Dealing with missing data
We planned to attempt to contact study authors to ask for missing data.
Assessment of heterogeneity
If sufficient included studies were identified, we planned to assess heterogeneity using the I2 statistic and the Chi2 test. If we found statistical heterogeneity, we planned to look for an explanation. Apart from the planned subgroup analyses detailed below, no other a priori specific potential causes of heterogeneity were explored.
Assessment of reporting biases
To determine whether selective reporting might have occurred, we planned to look for prespecified outcomes in trial registries and compare them with reported outcomes. If discrepancies were noted, we planned to attempt to contact the corresponding author.
In assessing for duplication bias, we planned to closely examine articles from repeated authors or sites and compare sample size, characteristics and details of studies. If overlap was apparent, we planned to attempt to contact the corresponding author.
If we were not successful in contacting study authors, we planned to include in our conclusions possible sources of reporting bias.
We planned to attempt to determine whether publication bias was present by plotting results of studies and determining whether they were published. If skewing was seen, with positive results being published and negative results not being published, we planned to report this.
We planned to determine the range of languages, locations and citation sources to examine potential bias.
Data synthesis
We planned to carry out an intention‐to‐treat analysis based on the first assigned method of phototherapy. For the meta‐analysis, we planned to report WMD and 95% CI for continuous variables. For categorical outcomes, we planned to report RR and 95% CI. For significant findings, we planned to report RD, NNTB and NNTH.
We planned to use the fixed‐effect model for meta‐analysis.
Subgroup analysis and investigation of heterogeneity
We planned to perform subgroup analyses if possible based on the following.
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Method of phototherapy.
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Fibreoptic.
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Conventional.
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Light‐emitting diode.
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Other.
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Duration of hospital‐based phototherapy before discharge for home phototherapy.
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No hospital phototherapy.
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Less than 24 hours of hospital phototherapy before discharge.
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More than 24 hours of hospital phototherapy before discharge.
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Age of initiation of home phototherapy.
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Criteria for readiness for home phototherapy, however defined in individual studies.
Sensitivity analysis
We planned to perform a sensitivity analysis (data permitting) to see whether results differ according to the quality of included studies (e.g. adequacy of randomisation: quasi‐randomised vs randomised).
Results
Description of studies
The above search strategy failed to identify any studies that met the predefined selection criteria.
Results of the search
All records identified in the electronic search could be excluded easily on the basis of title and abstract alone. No additional records were identified through other sources. The above search strategy failed to identify any studies that met the selection criteria.
Included studies
No study that could be included in this review was identified. No planned or ongoing studies were identified.
Excluded studies
No study that needed to be assessed for exclusion was identified.
Risk of bias in included studies
As no study was included, risk of bias was not assessed.
Allocation
As no study was included, allocation was not assessed.
Blinding
As no study was included, blinding was not assessed.
Incomplete outcome data
As no data were included, attrition bias could not be assessed.
Selective reporting
As no study was included, reporting bias could not be assessed.
Other potential sources of bias
As no study was included, no assessment for other sources of bias could be undertaken.
Effects of interventions
No study was included; therefore effects of interventions could not be determined.
Discussion
No studies that met the selection criteria for this review were identified. With the potential to use the new light‐emitting diode blanket systems, it is likely that home phototherapy is just as effective as hospital‐based systems. Potential problems with home phototherapy include increased risk of bilirubin encephalopathy, increased duration of phototherapy and increased risk of readmission to hospital. Home phototherapy is cheaper to perform than hospital‐based phototherapy, as it releases valuable bed space; however, it has the potential for increased costs due to required equipment and support personnel and risk of readmission. Home phototherapy may facilitate establishment of the parent‐infant bond. More research is required to assess the risks and benefits of home‐based phototherapy for non‐haemolytic jaundice in infants at more than 37 weeks' gestation.
Summary of main results
No studies met the predefined criteria for inclusion in this review.
Overall completeness and applicability of evidence
Not applicable, as no studies with predefined criteria were found.
Quality of the evidence
Not applicable, as no studies with eligible criteria were found.
Potential biases in the review process
Not applicable, as no studies with eligible criteria were found.
Agreements and disagreements with other studies or reviews
Not applicable, as no studies with eligible criteria were found.
