Can We Use a Transcutaneous Bilirubin Reading After Phototherapy?

Patient Presentation
A 4-day-old male came to clinic for his first examination after discharge from the newborn nursery. He was a full-term infant, born by normal spontaneous vaginal delivery to a G1P1 26 year old Asian mother who had a birth weight of 2958 grams. His hospital course had been complicated by a cephalohematoma of the left side of his head and hyperbilirubinemia that was close to meeting criteria for phototherapy at approximately 36 hours of life at 13.3 mg/dL (cut off 13.6 mg/dL). The team decided to treat him with phototherapy which he received for approximately 18 hours. At that time his serum bilirubin level was 10.6 mg/dL and then had rebounded to a level 6 hours later was 11.1 mg/dl. He was discharged home at approximately 60 hours of life with a weight that was 2825 grams (decreased 4.5%). He was breastfeeding every 2 hours with 4 wet diapers and several stool diapers that were transitioning. The past medical history showed that there was no ABO incompatibility, Coombs test was negative and he did not have sepsis symptoms. The family history was positive for cousins who had had hyperbilirubinemia as infants. The review of systems was negative.

The pertinent physical exam showed an alert male with weight of 2781 grams that was down 6% from birth weight. He examination was negative except for continued jaundice of his skin and eyes. The diagnosis of a well-appearing newborn with jaundice was made. A serum bilirubin level was obtained and was 13 mg/dL. He was sent home with follow up in 2 days. When staffing, the resident asked if a transcutaneous bilirubin could be used to evaluate the infant at this time after phototherapy. The attending remarked that there might be data about this question, but that he was unaware of an actual answer to it.

Discussion
Unconjugated hyperbilirubinemia in the newborn is a normal occurence. After birth the infant must rely on its own relatively immature liver to detoxify metabolites, the infant’s gastrointestinal tract also is not yet working as well for excretion, the infant is usually slightly fluid deficient before breastfeeding and/or bottle feeding are well established, and there is increased breakdown of red blood cells as the fetus has a higher hemoglobin than an infant and thus an infant is relatively hemoconcentrated. The total bilirubin rises from 1.5 mg/dL to 6.5 mg/dL (+ or -2.5 mg/dL) over the first 3-4 days of life. A differential diagnosis of neonatal unconjugated hyperbilirubinemia can be found here. A differential diagnosis of conjugated hyperbilirubinemia can be found here.

Phototherapy uses the skin to change the bilirubin to the more water-soluble lumirubin by using blue light at wavelengths of 420-480 nm. In doing so it causes blanching of the skin which obviously will change TcB levels. Factors which influence correlation between transcutaneous bilirubin (TcB) and total serum bilirubin (TsB) include skin color, TcB measurement body location, TsB level, the specific make and model of TcB bilirubinometer and if phototherapy has been used. Most professional guidelines currently advise against using TcB for determining hyperbilirubin level after phototherapy because of limited data that is available to determine the accuracy and clinical validity after phototherapy. However use of transcutaneous bilimeters in both inpatient and outpatient settings is more common today than in the past and questions about their appropriate use should be asked as clinical practices evolve.

Learning Point
Below are some recent studies that have tried to evaluate different aspects of how long after phototherapy could TcB be used to appropriately evaluate an infant for hyperbilirubinemia.

  • Tan and Dong in 2003 evaluated 70 neonates during and after phototherapy. They found that TcB and TsB were correlated at ~18-24 hours after phototherapy cessation.
  • Fonseca et.al. in 2012 evaluated 39 infants during and after phototherapy and attempted to correlate TcB performed in covered and uncovered skin areas with TsB. Overall, they found that TcB tested in skin-covered areas correlated with TsB but TcB in skin-exposed areas did not.
    They were only able to follow patients 6 hours after phototherapy cessation. Therefore they were not able to determine when recovery of skin color occurred as it had not occurred by end of the 6 hours.

  • Grabenhenrich et.al. in 2014 evaluated 86 term and preterm infants during and after phototherapy to determine the difference in TcB to TsB at different time periods during and after phototherapy. They calculated safety margins and found that “In the first 8 hours after treatment, TcB levels of -7.3 mg/dL below the individual phototherapy threshold allowed safe rejection of confirmatory blood sampling. After 8 hours, that safety margin was reduced to approximately -5.0 mg/dL.”
  • Juster-Reicher et.al. in 2015 in a study similar to Tan and Dong, evaluated 371 term infants and followed paired TcB and TsB measurements up to 9 days of life. They found that TcB and TsB measurements correlated 8 hours after cessation of phototherapy.

Questions for Further Discussion
1. How do you use TcB in your clinical practices and when do you correlate with a TsB?
2. What helps you determine when and if a patient may need phototherapy or other treatment for neonatal jaundice?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Jaundice and Common Infant and Newborn Problems.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Tan KL, Dong F. Transcutaneous bilirubinometry during and after phototherapy. Acta Paediatr. 2003;92(3):327-31.

American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul;114(1):297-316.

Fonseca R, Kyralessa R, Malloy M, Richardson J, Jain SK.
Covered skin transcutaneous bilirubin estimation is comparable with serum bilirubin during and after phototherapy.
J Perinatol. 2012 Feb;32(2):129-31.

Grabenhenrich J, Grabenhenrich L, Buhrer C, Berns M.
Transcutaneous bilirubin after phototherapy in term and preterm infants. Pediatrics. 2014 Nov;134(5):e1324-9.

Juster-Reicher A, Flidel-Rimon O, Rozin I, Shinwell ES. Correlation of transcutaneous bilirubinometry (TcB) and total serum bilirubin (TsB) levels after phototherapy. J Matern Fetal Neonatal Med. 2014 Sep 30:1-3.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

Why Does Aspartame Have a Warning Label?

Patient Presentation
A pediatrician’s teenage son who was studying chemistry was reading the ingredient label on a carbonated beverage can and said, “There’s several things here that I can’t even pronounce, but why does it have a specific warning for this thing called aspartame?” The pediatrician smiled and said, “That is an interesting story about using microbiology and chemistry for trying to identify and stop a disease called Phenyloketonuria or PKU before it can hurt babies.” She then went on to briefly explain the history of PKU screening and how it’s linked to the artificial sweetener aspartame.

Discussion
Phenylketonuria (PKU) is an autosomal recessive genetic disease. The PAH gene is found on chromosome 12 and has more than 600 mutations associated with it. The incidence varies but PKU is primarily found in Caucasian populations. The PAH gene codes for phenylalanine hydroxylase (PAH) which catalyzes the amino acid phenylalanine (Phe) to tyrosine. PAH uses a cofactor called tetrahydrobiopterin (BH4) in this process. With a deficiency in PAH, Phe accumulates and can cause severe cognitive impairment and global developmental delay, microcephaly, seizures, poor growth and poor skin pigmentation. Tyrosine also decreases and along with it its products of melanin, L-thyroxine and catecholamine neurotransmitters. The exact cause of the PKU clinical problems may be an accumulation of Phe, deficiency in Tyrosine products or another cause but is unknown exactly currently.

The mainstay of treatment is a low protein, low phenylalanine diet. Phe is an essential amino acid so some Phe must be supplied in the diet but the amount is highly individualized based on the specific mutation, age and other specific needs of the individual. Specialized formula that is Phe-free is used for infants with children and adults using similar alternative formulas as part of their overall diet. The diet centers on consuming mainly fruits and vegetables. Low protein grains are also used, along with much smaller amounts of whole proteins along with Phe-free formulas. Food products for medical diets are more commonly available in recent years with reportedly improved taste and variety, but they can also be more expensive to purchase. Phe blood levels are monitored closely and changes in the diet are made to provide enough but not too much Phe in the diet. A dietician is critical for assisting the patient and family with the diet. The diet is usually recommended throughout the patient’slifetime but in some cases is less restrictive when the patient is an older child or adult.

Other potential treatments for individual patients include Sapropterin dihydrochloride, a BH4 agonist, enzyme replacement therapy, large neutral amino acid therapy (a competitive carrier of Phe) and gene therapy.

Because PKU is autosomal recessive, the risk in subsequent pregnancies with the same parents is 25%. Female PKU patients who themselves wish to have families of their own have their own challenges. The risk of PKU in her partner is low and therefore there is a relatively low risk of her having a child with PKU (~2% in North American populations) but the child will at least carry the gene. The bigger risk is that Phe is actively transported across the placenta so the fetal level exceeds the mother’s level. High levels of Phe can be devastating to the fetus causing severe developmental delay, seizures, congenital heart defects and other problems. Therefore there are strict recommendations for female PKU patients to begin a strict diet before they wish to become pregnant and during the pregnancy to mitigate any of these effects.

Learning Point
Aspartame (L-aspartyl-L-Phemethyl ester) is an artificial sweetener that metabolizes to Phe, L-aspartic acid and methanol. It was first discovered in 1965, and approved by the US Federal Drug Administration in 1981. It is commonly used in a huge number of foods, drinks, candy, desserts, gum/mints etc worldwide, but is also in medicines, vitamins and skim milk powder. All medication formulations must be checked before they can be used by patients, and as formulations change often they need to be checked each time the medication is dispensed. A pharmacist is important member of the patient’s care team.

PKU was first described by Asbjørn Følling (1888-1973) in 1934. In the late 1950’s Dr. Robert Guthrie (1916-1995) developed an easy to do diagnostic test using blood spots on special filter paper (often called Guthrie cards) to detect the level of Phe by a bacterial inhibition assay. This was introduced into clinical practice in the 1960s because it was simple, inexpensive and cost-effective; it has become the quintessential test for preventative screening. Over time, testing for PKU became standard in all 50 US states, and many countries across the world. Because of its success, additional tests have been added to the blood spot or newborn screening (exact diseases tested for vary by location) and the methods of detection have changed with the advances in technology. Tandem mass spectrometry is currently used to detect PKU.

Questions for Further Discussion
1. What diseases do your newborn screening test screen for?
2. For patients that have a positive newborn screening test, howare they contacted and appropriate followup managed? What is the general practitioner’s role in this process?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Phenylketonuria

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Williams RA, Mamotte CDS and Burnett JR. Phenylketonuria: An Inborn Error of Phenylalanine Metabolism. Clin Biochem Rev. 2008 Feb; 29(1): 31-41.

Casey L. Caring for children with phenylketonuria. Can Fam Physician. 2013 Aug;59(8):837-40.

Brosco JP, and Paul DB. The Political History of PKU: Reflections on 50 Years of Newborn Screening. Pediatrics. 2013 Dec; 132(6): 987–989.

Groselj U, Tansek MZ, Battelino T. Fifty years of phenylketonuria newborn screening – A great success for many, but what about the rest? Mol Genet Metab. 2014 Sep-Oct;113(1-2):8-10.

Sharman R, Sullivan KA, Jones T, Young RM, McGill J. Executive functioning of 4 children with hyperphenylalaninemia from childhood to adolescence. Pediatrics. 2015 Apr;135(4):e1072-4.

Committee Opinion No: 636: Management of women with phenylketonuria. Obstet Gynecol. 2015 Jun;125(6):1548-50.

Aspartame. Wikipedia.
Available from the Internet at https://en.wikipedia.org/wiki/Aspartame (rev. 11/1/2015, cited 12/4/15).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

Is Coconut Oil Really Helpful as a Topical Antibacterial Agent?

Patient Presentation
An 8-year-old male came to clinic with pharyngitis, rhinorrhea and cough for 2 days. He had a mild fever and was drinking. The past medical history showed that he had atretic nasolacrimal ducts that easily caused build up of mucoid discharge when he had upper respiratory illness. The pertinent physical exam showed a mildly ill male with normal temperature and vital signs. His eyes had clear/mucoid discharge that was somewhat matted on his eyelashes, but did not appear purulent. He had clear nasal discharge and his throat showed erythematous tonsils with two small white patches. His ears and lungs were clear. The laboratory evaluation was negative for a rapid strep test and a throat culture was sent to the laboratory.

The diagnosis of of an upper respiratory tract infection with pharyngitis was made. The physician said, “This looks like a viral infection but we will continue to monitor the throat culture. I don’t think your eyes have a bacterial infection but are just real watery.” The mother said, “Yeah, this is how his eyes look when he has a cold. They may look a little worse because we have been using coconut oil on his eyelids. It seems to help protect his skin from all the tears and goop he gets. Plus it’s easier to wipe it off. I’ve also read that it acts kind of like an antibiotic. Anyways it seems to help when he has a cold.” The pediatrician noted that the coconut oil didn’t seem to be hurting anything, and noted to herself that another parent said that she was using coconut oil for her daughter’s atopic dermatitis.

Discussion
Coconut oil along with many other plant oils are used by humans for many reasons. It is often used as a food ingredient either as an ingredient or in food preparation such as frying. It is also used topically and applied to skin, hair or nails to provide protection or help improve their condition. Some people use it for hygiene such as rinsing their mouths while others ingest it like a medication as they feel it improves various acute or chronic diseases.

There are relatively few scientific studies of coconut oil use in children or even adults. A PubMed search on 11/23/15 of coconut oil in human children with ages birth to 18 years found only 57 articles from 1973-2015. On the same day the American Academy of Pediatrics website (aap.org) was searched and found coconut oil being used as part of a healthy diet. Similarly, the Cochrane Collaboration (cochrane.org) and the National Guideline Clearinghouse (http://www.guidelines.gov) returned no results about coconut oil when searched. The National Institutes of Health National Center for Complementary and Integrative Medicine (https://nccih.nih.gov) also does not list coconut oil as one of its health topics. The Federal Drug Administration (fda.org) regards coconut oil as GRAS or generally recognized as safe and specifically states that “[n]one of the available biological information indicates that these substances are hazardous to man or animals even when consumed at levels that are orders of magnitude greater than could result form their use….”

Learning Point
There’s little research that supports the use of coconut oil specifically as an antibacterial agent. Those studies that are available recently have small numbers. A 2007 study found that coconut oil had in-vitro activity against Candida species. A 2008 study found that coconut oil did have improved antibacterial effects for Staphylococcus aureus compared to olive oil in adult atopic dermatitis patients (N=52 for total study patients). A 2013 study found that two coconut oils did not have antibacterial effects for Staphylococcus aureus in rodents.

Preterm infant massage therapy studies have found some benefits to using coconut oil in addition to the massage itself. Infants had greater weight gain possibly because of transdermal absorption of the oil which then potentially could be used as a nutritional source by the infant. Another study also found better thermoregulation.

Questions for Further Discussion
1. What resources do you use for information about nutritional supplements or complementary and integrative medicine?
2. What plant, petroleum or synthetic oils do you prescribe and for what uses?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Herbal Medicine

Information prescriptions for patients can be found at MedlinePlus for these topics: Topics and Complementary and Integrative Medicine.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Ogbolu DO, Oni AA, Daini OA, Oloko AP. In vitro antimicrobial properties of coconut oil on Candida species in Ibadan, Nigeria. J Med Food. 2007 Jun;10(2):384-7.

Verallo-Rowell VM, Dillague KM, Syah-Tjundawan BS. Novel antibacterial and emollient effects of coconut and virgin olive oils in adult atopic dermatitis. Dermatitis. 2008 Nov-Dec;19(6):308-15.

Field T, Diego M, Hernandez-Reif M. Preterm infant massage therapy research: a review. Infant Behav Dev. 2010 Apr;33(2):115-24.

Manohar V, Echard B, Perricone N, Ingram C, Enig M, Bagchi D, Preuss HG. In vitro and in vivo effects of two coconut oils in comparison to monolaurin on Staphylococcus aureus: rodent studies. J Med Food. 2013 Jun;16(6):499-503.

Federal Drug Administration. Select Committee on GRAS Substances (SCOGS) Opinion: Coconut oil, peanut oil, oleic acid (packaging), and linoleic aid.
Available from the Internet at http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/SCOGS/ucm261259.htm (rev. 9/29/2015, cited 11/23/15).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital