NEONATOLOGY UPDATE
Sunlight Is OK for Neonatal Jaundice, Provided UV Rays Are Filtered Out
Keeping babies out in the sun but protected from harmful UV rays is an effective and affordable option for treating neonatal jaundice in resource-poor settings, according to a new study from Nigeria.
"It is very, very exciting to be able to treat jaundice in newborns in the face of large areas of Nigeria and Africa without access to any phototherapy because of problems with both electricity and equipment," lead author Dr. Tara Slusher from the University of Minneapolis, Minnesota, said in her email to Reuters Health.
She is "not quite ready" to recommend this method as the treatment of choice, however. She says more study is needed to determine how to employ it with less monitoring in very rural settings.
As reported May 26 online in Pediatrics, the researchers enrolled 227 neonates born at the Island Maternity Hospital in Lagos, Nigeria, who developed jaundice within the first 14 days of life.
Babies with serum bilirubin levels within 3 mg/dL of the American Academy of Pediatrics(AAP) recommended treatment levels received the filtered sunlight phototherapy for five to six a day. (The AAP guidance for calculating treatment levels is here: http://pediatrics.aappublications.org/content/114/1/297.full.)
Systemically unwell neonates or with severe jaundice needing exchange transfusion were excluded. Serum bilirubin was estimated daily.
Filtered sunlight phototherapy (FS-PT) was improvised using a metal frame covered with commercial plastic sun-control film costing approximately $300. The Air Blue 80 film (CP Films, Fieldale, VA) transmitted 79% of blue light and was used on cloudy days, while the Gila Titanium (CP Films, Inc) that allowed 33% of blue wavelength light was used on sunny days. Both films cut out most of the harmful UV radiation. Babies were placed under the canopy which was exposed to sunlight.
Effective phototherapy was defined as any fall in bilirubin levels among babies older than 3 days or a rise of less than 0.2 mg/dL/ hr in younger babies. FS-PT was discontinued when bilirubin declined below 12 mg/dL.
The mean gestation age of the study group was 38 weeks. The mean age at admission was 36 hours of age with a mean total bilirubin of 7.9 mg/dl. Overall, babies received FS-PT for mean of 1.13 days with a cumulative total of 257 treatment days for the group.
FS-PT provided effective phototherapy on 92% of the 197 of treatment days for which pre and post bilirubin levels were available, with an average bilirubin decline of 0.06 mg/dL per hour.
Adverse effects were restricted to temperature fluctuations needing transient interruptions to the FS-PT. No cases of sunburn or dehydration were reported.
In email to Reuters Health, neonatologist Dr. VinodBhutani from Stanford University in California called the results "a brilliant promising first step that can be used as a complement to minimize overcrowding in a neonatal units."
It is not yet the treatment of choice, he added, because "further studies for best modes of delivery (need to be done) and cost-effectiveness needs to be evaluated." Prof. Bhutani was not part of the study team.
FS-PT will be most effective in places with good sunlight for most of the year, the researchers say. Assembling the apparatus was challenging - with the need to import the film and manufacture the canopy locally. Cold and inclement weather could limit the use of the equipment, they admit.
Dr. Slusher recommended larger studies in remote areas and in babies with severe jaundice. "We believe it will be a valuable addition to the treatment options available for neonatal jaundice in resource poor setting and it some locales likely the only option," she concluded.
(Pediatrics 2014, http://bit.ly/1kOPkiM)
Hypoxia in Preemies: How Long Should Caffeine Be Used?
Intermittent hypoxia -- brief, repetitive episodes of low hemoglobin oxygen saturation -- are usually not apparent clinically. However, animal studies have demonstrated that intermittent hypoxia may be proinflammatory and contribute to some of the complications seen in premature infants, including retinopathy of prematurity. Although caffeine is used in many infants to address apnea of prematurity (the effects of which are much more clinically evident), few data demonstrate whether caffeine has a role in treating intermittent hypoxia that can persist after resolution of apnea of prematurity.
In Rhein and colleagues' study, preterm infants were enrolled at 16 sites in 2010-2011. All infants were born at 25-32 weeks' gestational age and had received treatment with caffeine. Infants were enrolled when they reached 33 postmenstrual weeks if they had no congenital or genetic disorders and no severe ongoing complications of prematurity that would otherwise affect results. The infants were all breathing room air with good oxygen saturation levels at the time of enrollment and had been off of caffeine for at least 5 days.
Once the infants reached at least 34 weeks' postmenstrual age, they were randomly assigned to either the treatment or placebo group. The treatment group received a 20-mg/kg loading dose of caffeine, followed by a daily dose of 6 mg/kg. Caffeine levels were not assessed in this study.
All infants were placed on pulse oximetry monitors, but the monitors neither alarmed nor displayed values for caregivers or medical providers to see. The study endpoint was reached when the infant was home after hospital discharge for 1 week or the infant reached 40 weeks' postmenstrual age.
Intermittent hypoxia was defined as any oxygen saturation level at least 5% below the infant's resting oxygen saturation level or < 90% for at least 5 seconds. Two primary outcomes were evaluated: the average number of intermittent hypoxia events per hour and the total seconds of saturation < 90% in each infant. The outcomes were stratified by postmenstrual week. Infants were also stratified by gestational age at birth into 2 groups: < 29.5 weeks and > 29.5 weeks.
The analysis groups included 53 infants who were assigned to the control group and 42 assigned to the caffeine group. Three additional infants assigned to the caffeine group had insufficient data for analyses.
Study Findings
Across each postmenstrual age week, the infants who received caffeine demonstrated fewer episodes of intermittent hypoxia and spent less time, on average, below 90% oxygen saturation. For example, at 35 weeks' postmenstrual age, infants in the treatment group experienced 3.6 episodes of intermittent hypoxia per hour of recording compared with 8.4 episodes in the placebo group. This represented 52% fewer episodes. Similarly, the treatment group experienced 50.9 seconds per hour of saturation < 90% compared with 106 seconds among the placebo group.
The general pattern of less frequent episodes of intermittent hypoxia and reduced mean time with saturations < 90% was present across all postmenstrual age weeks, but the differences only reached statistical significance in the groups at 35 and 36 weeks' postmenstrual age. Although the pattern held for infants of 37, 38, and 39 weeks' postmenstrual age, the 95% confidence intervals for those differences all included 1. That said, even at 39 weeks' postmenstrual age, treatment group infants experienced 2.2 episodes of intermittent hypoxia per hour of recording vs 3.0 episodes per hour among the placebo group, but each group experienced approximately 40 seconds of oxygen saturation < 90% per hour of recording.
In 5 of the treatment infants, caffeine was discontinued as a result of tachycardia, but no other significant adverse events were noted. Rhein and colleagues conclude that extended treatment with caffeine for premature infants previously treated with caffeine can reduce the frequency and duration of intermittent hypoxia episodes.
Viewpoint
I'll go out on a limb and presume that many pediatric providers won't be thrilled at the prospect of premature infants spending even more time on caffeine, but these are results are very eyebrow-raising. The authors are very careful to comment that this study measures an intermediate outcome: reduction of potentially harmful events. In their discussion, they comment that it would be very important to demonstrate that the reduction of intermittent hypoxia actually produces clinical benefits, such as improved neurologic or other outcomes, in premature infants. They also allude to data from other studies that suggest that caffeine doses may have to be adjusted for older premature infants, those above 36 weeks' gestation, as a potential explanation for why the differences in intermittent hypoxia among the older infants did not reach statistical significance.
(Rhein LM, Dobson NR, Darnall RA, et al; Caffeine Pilot Study Group, JAMA Pediatr. 2014;168:250-257)
Neonatal Sepsis as a Risk Factor for Neurodevelopmental Changes in VLBW Preterm Infants
To evaluate neonatal sepsis as a risk factor for abnormal neuromotor and cognitive development in very low birth weight preterm infants at 12 months of corrected age.
Methods
This was a prospective cohort study that followed the neuromotor and cognitive development of 194 very low birth weight preterm infants discharged from a public neonatal intensive care unit. The Bayley Scale of Infant Development (second edition) at 12 months of corrected age was used. The outcomes were the results of the clinical/neurological evaluation and the scores of the psychomotor development index (PDI) and mental development index (MDI) of the Bayley Scale of Infant Development II. The association between neonatal sepsis and neuromotor development and between neonatal sepsis and cognitive development was verified by logistic regression analysis.
Results
mean birth weight was 1,119 g (SD: 247) and mean gestational age was 29 weeks and 6 days (SD: 2). Approximately 44.3%(n = 86) of the infants had neonatal sepsis and 40.7% (n = 79) had abnormal neuromotor development and/or abnormal psychomotor development index (PDI < 85) at 12 months of corrected age. On the mental scale, 76 (39.1%) children presented abnormal cognitive development (MDI < 85). Children with neonatal sepsis were 2.5 times more likely to develop changes in neuromotor development (OR: 2.50; CI: 1.23R08;5.10). There was no association between neonatal sepsis and cognitive development impairment.
Conclusion
Neonatal sepsis was an independent risk factor for neuromotor development impairment at 12 months of corrected age, but not for mental development impairment.
(Rachel C. Ferreiraa, Rosane R. Melloa, et al. J Pediatr (Rio J). 2014; 90:293-9.)
Surfactant Protein-D–Encoding Gene Variant Polymorphisms Are Linked to Respiratory Outcome in Premature Infants
Associations between the genetic variation within or downstream of the surfactant protein-D–encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to investigate whether SFTPD variations affect serum SP-D levels in infants and pulmonary outcome in premature infants.
Study design
Serum SP-D levels were measured in 211 mature and 202 premature infants, and 7 SFTPD single-nucleotide polymorphisms (SNPs) were genotyped. SNP analysis and haplotype analysis were used to associate genetic variation to SP-D, respiratory distress (RD), oxygen requirement, and respiratory support.
Results
The 5R42;-upstream SFTPD SNP rs1923534 and the 3 structural SNPs rs721917, rs2243639, and rs3088308 were associated with the SP-D level. The same SNPs were associated with RD, a requirement for supplemental oxygen, and a requirement for respiratory support. Haplotype analyses identified 3 haplotypes that included the minor alleles of rs1923534, rs721917, and rs3088308 that exhibited highly significant associations with decreased SP-D levels and decreased ORs for RD, oxygen supplementation, and respiratory support.
Conclusion
These findings extend and validate previous observations of SFTPD association with the risk of respiratory outcomes and suggest SFTPD as an essential factor affecting pulmonary adaptation in premature infants. (GrithLykke Sorensen, et al. J Pediatr. 2014;165:683-9.)