Antenatal Betamethasone: A Prolonged Time Interval from Administration to Delivery Is Associated with an Increased Incidence of Severe Intraventricular Hemorrhage in Infants Born before 28 Weeks Gestation



Melissa Liebowitz, MD
Ronald I. Clyman, MDPress enter key for correspondence informationPress enter key to Email the author

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To examine the effects of antenatal steroids on severe intraventricular hemorrhage (IVH) in infants born during the IVH vulnerable period (<28 weeks gestational age) and to evaluate rates of IVH correlated with the time interval between treatment or retreatment and birth.



Study design

A total of 429 infants (<28 weeks gestation), who delivered ≥24 hours after the first betamethasone (BMZ) course (2 doses), were divided into groups based on the interval between the first course of BMZ and delivery: <10 days or ≥10 days. The primary outcome was severe IVH. Multiple regression analyses were performed to adjust for potential confounders.



Three hundred ninety-two infants delivered after a single BMZ course (312 delivered <10 days; 80 ≥10 days). The incidence of severe IVH was 17% for infants delivered ≥10 days and 7% for those delivered <10 days after a single BMZ course (aOR 4.16; 95% CI 1.59-10.87, P = .004); 37 infants (born ≥10 days from the first BMZ course) received a second/rescue BMZ course. The incidence of severe IVH among infants receiving a second/rescue course was 8%, which was similar to the incidence among infants born <10 days (aOR 1.7; 95% CI 0.41-6.6, P = .48).




In infants born before 28 weeks gestation, delivery ≥10 days from the first BMZ course is associated with a higher incidence of severe IVH; a second/rescue course may reverse this effect.




Antimicrobial resistance - a threat to neonate survival



Description: A new study has found that sepsis accounts for nearly a quarter of new-born deaths in India, with most of episodes occurring within 3 days of birth. The infecting pathogens had an alarming degree of antimicrobial resistance.



A new study has found that sepsis accounts for nearly a quarter of new-born deaths in India, with most of episodes occurring within 3 days of birth. The infecting pathogens had an alarming degree of antimicrobial resistance.



The most infection-related deaths in the neonatal period are high in low- and middle-income countries like India. Yet there is a lack of data on neonatal sepsis rates in these countries.



The Delhi Neonatal Infection Study (a prospective cohort study) was conducted at three tertiary care hospitals in New Delhi from July 2011 to February 2014. From 88,636 live births, 13,530 newborns were enrolled in the study after admission to a neonatal intensive care unit (NICU), and 1,934 had a final diagnosis of sepsis. The incidence of total sepsis was 14.3%, early onset sepsis was common with nearly two-thirds of cases occurring within 72 h of birth. Sepsis was the underlying cause of death in 24% of the enrolled new-borns who died during the study.



Analysis of clinical isolates found that 64% were gram-negative bacteria, with Acinetobacter spp (22%) being the most common, followed by Klebsiella (17%) and Escherichia coli (14%). High rates of multidrug resistance were observed in all three pathogens, with 82% of Acinetobacter isolates, 54% of Klebsiella isolates, and 38% of E coli isolates showing resistance to commonly used antibiotics and extended-spectrum antibiotics such as cephalosporins and carbapenems.



The study highlights the need to undertake research to understand the pathogenesis of early-onset sepsis and to devise measures to prevent related morbidity and mortality



Source: Investigators of the Delhi Neonatal Infection Study (DeNIS) collaboration. Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study.



(Reference: Lancet Glob Health. 2016;4(10):e752-60)



Bosentan as Adjunctive Therapy for PPHN of the Newborn









To evaluate the efficacy, safety, and pharmacokinetics of the endothelin receptor antagonist bosentan as adjunctive therapy for neonates with persistent pulmonary hypertension of the newborn (PPHN).




Study design




This was a phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE-4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled nitric oxide (iNO) treatment (≥4 hours), and had persistent respiratory failure (oxygenation index [OI] ≥12). After 2:1 randomization, bosentan 2 mg/kg or placebo was given by nasogastric tube twice daily for ≥48 hours and up to 1 day after iNO weaning.








Twenty-one neonates received a study drug (13 bosentan, 8 placebo). Compared with the placebo group, the group treated with bosentan had a higher median baseline OI and greater need for vasoactive agents. One treatment failure (need for extracorporeal membrane oxygenation) occurred in the group treated with bosentan. The time to weaning from iNO or mechanical ventilation was not different between the groups. Bosentan was well tolerated and did not adversely affect systemic blood pressure or hepatic transaminase levels. Anemia and edema were more frequent in patients receiving bosentan. Blood concentrations of bosentan were low and variable on day 1, and achieved steady state on day 5.








Adjunctive bosentan was well tolerated, but did not improve oxygenation or other outcomes in our patients with PPHN. This effect may be related to delayed absorption of bosentan on treatment initiation in critically ill neonates or to more severe illness of the neonates who received bosentan.




(Robin H. Steinhorn et al. J Pediatr. 2016 Oct;177:90-96.e3)





Dose-Dependent Benefits of Antenatal Steroids in Preemies



By Megan Brooks



October 11, 2016



NEW YORK (Reuters Health) - Results of a large study support antenatal steroid (ANS) administration in extremely premature babies and the goal should be to give a complete course before delivery, researchers say.



The study found that ANS protects against death and neurodevelopmental impairment (NDI) in a dose-dependent fashion in babies born at 22 to 27 weeks gestational age weighing between 401 and 1000 g.



The findings support ANS administration "even in situations where the likelihood of a complete course of antenatal steroids is low because of insufficient time due to imminent delivery, as even an incomplete course of steroids before birth was associated with significantly lower rates of death, complications in the neonatal period such as severe bleeding in the brain and lower neurodevelopmental impairment," lead author Dr. Sanjay Chawla, from the Children's Hospital of Michigan and Hutzel Women's Hospital in Detroit, told Reuters Health by email.



The study published online October 10 in JAMA Pediatrics evaluated 6,121 extreme preemies born at participating sites of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network between 2006 and 2011.



They were grouped retrospectively based on ANS exposure: 848 had no ANS exposure, 1,581 had a partial course of ANS, and 3,692 had a complete course. They were followed from birth to about age two.



Among all 6,121 infants, 4,284 (70%) survived to 18- to 22-month follow-up. Data on neurodevelopmental outcomes and neonatal morbidities were available for 3,892 (91%).



The researchers found significant between-group differences in survival, complications in the neonatal period - including severe intracranial hemorrhage (ICH), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) - and neurodevelopmental outcomes (cerebral palsy, cognitive impairment).



"Infants in the complete steroid treatment group had the best outcome," Dr. Chawla told Reuters Health. "Infants in the incomplete treatment group had significantly lower death, neonatal complications and neurodevelopmental impairment, as compared to infants without any exposure to antenatal steroids." There were dose-dependent benefits of ANS for infants born even at 23 weeks of gestation, he said.



Mortality rates in the no, partial, and complete ANS groups were 43.1%, 29.6%, and 25.2%, respectively. Rates of severe ICH among survivors were 23.3%, 19.1%, and 11.7%, respectively; death or NEC - 48.1%, 37.1%, and 32.5%; and death or BPD - 74.9%, 68.9%, and 65.5%.



The primary outcome of death or NDI occurred in 68.1% of infants with no ANS exposure, 54.4% of infants with partial exposure and 48.1% of those with a complete ANS course (p<0.001). Death and NDI were both separately higher with no ANS exposure compared with partial and complete exposure.



On logistic regression analysis, compared with no ANS, complete and partial ANS courses were associated with a lower likelihood of death or NDI (odds ratios, 0.63 and 0.77).



"The improved neurodevelopmental outcome with a complete course of antenatal steroids was partly related to a reduction in severe bleeding in the brain," the investigators report.



"To our knowledge, the current study differs from other follow-up studies with respect to details on dose of ANS exposure and comparison of outcomes in relation to no, partial, and complete ANS courses," they say.



Given the dose-dependent protective effects of ANS, the investigators say a study is needed to test whether an accelerated course would improve neonatal outcomes when time does not permit completion of a conventional course.



The study was funded by the National Institutes of Health. The authors have disclosed no conflicts of interest.




JAMA Pediatr 2016.



Heated, Humidified High-Flow Nasal Cannula Effective for RDS of Prematurity



A heated, humidified high-flow nasal cannula (HHHFNC) has similar efficacy and safety to nasal continuous positive airway pressure (nCPAP) in infants with respiratory distress syndrome (RDS) of prematurity, according to a noninferiority trial.



"HHHFNC can be a valid option for managing mild to moderate RDS in preterm infants older than 28 weeks of gestation considering its benefits, such as ease of use and improved patient comfort," Dr. Anna Lavizzari from Universita degli Studi di Milano, Milan, Italy told Reuters Health by email.



nCPAP is commonly used for early respiratory management of preterm infants. HHHFNC is increasingly popular as an alternative form of noninvasive respiratory support, but there have been only a few large randomized controlled trials to assess its efficacy in newborns.



Dr. Lavizzari's team evaluated HHHFNC when applied exclusively as a primary approach to mild to moderate RDS in a prospective unblinded trial of 316 infants older than 28 weeks' gestational age.



Failure of noninvasive respiratory support within 72 hours from the beginning of the study, the primary outcome, occurred in 17 of the 158 infants in the HHHFNC group (10.8%) and in 15 of the 158 infants in the nCPAP group (9.5%), a difference that fell within the predefined noninferiority margin.



Failure rates did not differ significantly between the two modes in any of the gestational age strata, according to the August 8th JAMA Pediatrics online report.



Nor did the two treatment groups differ significantly in any of the secondary respiratory outcomes: overall duration of respiratory support, days of noninvasive respiratory support, days of oxygen supplementation, need for surfactant, duration of caffeine treatment, and rate of bronchopulmonary dysplasia.



Air leaks were uncommon, and the groups did not differ significantly in the rates of other adverse events or complications of prematurity.



"In our clinical practice, we still prefer nasal CPAP and BiPAP as first approach to RDS in younger infants who tend to have more severe RDS and who may need more pressure support," Dr. Lavizzari said.



"Further research should also assess the role of HHHFNC in the respiratory management of infants of lower gestational age and in other respiratory disorders of newborn infants, as well as evaluate how to optimize this technique," she added. "Additional studies should also measure the economic impact of HHHFNC versus other noninvasive respiratory support. Assessing the feasibility and safety of HHHFNC in limited-resource countries should also be done."



Dr. Suma B. Hoffman from University of Maryland Hospital for Children in Baltimore told Reuters Health by email, "In more mature neonates requiring respiratory support HHHFNC is an adequate alternative to nCPAP; however, given other reports in the literature, caution should still be exercised when applying this modality to the less mature population."



"I feel that nCPAP should be favored in the less mature population, especially those under 28 weeks' gestation," she explained. "Several studies, including my own, have shown a higher number of days requiring respiratory support when HHHFNC is used versus nCPAP. I feel that less mature lungs require stable measurable pressure for growth and support that HHHFNC is not equipped to provide."



Dr. Stamatia Alexiou from The Children's Hospital of Philadelphia, Pennsylvania told Reuters Health by email, "In addition to providing distending pressure, HHHFNC has been shown to reduce metabolic demand and decrease resistance in the nasopharynx, which may add to its efficacy in supporting these neonates."



"Given concerns regarding the absence of a pressure-limiting valve in HHHFNC circuits, nCPAP may be preferred in patients requiring higher distending pressures," she said. "It should also be preferred in facilities where clinicians may not be as comfortable using high-flow therapy."



SOURCE: JAMA Pediatr 2016;




Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial



Portions of this study were presented as an abstract at the 30th International Workshop on Surfactant Replacement, Stockholm, Sweden, June 5-6, 2015; 1st Congress of joint European Neonatal Societies (jENS), Budapest, Hungary, September 16-20, 2015; and Pediatric Academic Societies (PAS), Baltimore, MD, April 30-May 3, 2016.



Pia Härkin, MD





Antti Härmä, MD



Outi Aikio, MD, PhDDescription: correspondencePress enter key for correspondence information


Description: emailPress enter key to Email the author





Marita Valkama, MD, PhD





Markku Leskinen, MD, PhD





Timo Saarela, MD, PhD





Mikko Hallman, MD, PhD



PEDEGO Research Center, and MRC Oulu, University of Oulu, and the Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland



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To study the biologic effect of paracetamol, an inhibitor of prostaglandin synthase, on early closure of ductus arteriosus, and to evaluate possible adverse effects associated with the drug.



Study design



In a controlled, double-blind, phase I-II trial, very low gestational age (<32 weeks) infants requiring intensive care were randomly assigned to intravenous paracetamol or placebo (0.45% NaCl). A loading dose of 20 mg/kg was given within 24 hours of birth, followed by 7.5 mg/kg every 6 hours for 4 days. Daily cardiac ultrasound examinations of ductal calibers were performed before the first dose, and until 1 day after the last dose. The main outcome was a decrease in the ductal caliber without side effects.






Of 63 screened infants, 48 were randomized: 23 were assigned to paracetamol and 25 to placebo. Before the intervention, their ductal calibers were similar. During the intervention, the ductus closed faster in the paracetamol group (hazard ratio 0.49, 95% CI 0.25-0.97, P = .016). The mean (95% CI) postnatal ages for ductal closure were 177 hours (31.1-324) for the paracetamol-treated vs 338 hours (118-557) for controls (P = .045). Paracetamol serum levels were within the therapeutic range, and no adverse effects were evident.






Prophylactic paracetamol induced early closure of the ductus arteriosus without detectable side effects. Further trials are required to determine whether intravenous paracetamol may safely prevent symptomatic patent ductus arteriosus.




Pediatric Infectious Disease Journal:



November 2016 - Volume 35 - Issue 11 - p 1211–1214



doi: 10.1097/INF.0000000000001263



Antimicrobial Reports



Pharmacokinetics of Colistin Following a Single Dose of Intravenous Colistimethate Sodium in Critically Ill Neonates



Nakwan, Narongsak MD; Usaha, Siripa MD; Chokephaibulkit, Kulkanya MD; Villani, Paola BiolD; Regazzi, Mario PharmD; Imberti, Roberto MD



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In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (±SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 ± 0.7 µg/mL and 25.3 ± 10.4 µg·h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 ± 0.9 hours, 9.0 ± 6.5 hours, 7.7 ± 9.3 L/kg and 0.6 ± 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 ± 0.4 µg/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient.




Steroid Treatment in Very Low Birth Weight Infants May Contribute to Vision Problems



In a study in the Journal of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS), researchers found that for very premature infants with birth weights of less than 500 grams, the use of corticosteroids resulted in a 1.6 times increased risk for retinopathy of prematurity (ROP) and a 1.7 times greater chance for advanced ROP.



Data on 1,472 neonates discharged from 167 neonatal intensive care units between 1996 and 2013 were collected from the Pediatrix BabySteps Clinical Data Warehouse, a large scale database of infant health records. Although this database contains information on more than 1.1 million infants, investigators restricted their analysis to extremely premature infants, with birthweights at the very lower limit of viability. These particular infants are at greatest risk for disorders associated with prematurity. Neonates in the study met 3 primary criteria: birth weight of less than 500 grams, discharged from hospital alive, and availability of ophthalmic ROP examination results. Diagnoses of ROP were standardised according to the International Classification of Retinopathy of Prematurity.



According to lead investigator Tammy Z. Movsas, MD, MPH, Midland County Department of Public Health, Midland, Michigan and Michigan State University, School of Human Medicine, East Lansing, Michigan, "Our study group consists of premature infants with birthweights at the lowest level that is compatible with life. This group represents a more homogeneous set of neonates than in other studies that consist of premature infants with a broader range of birthweights. Neonates at these critically low birth weights (and gestational ages) are at the absolute highest vulnerability for a host of neonatal morbidities including ROP and bronchopulmonary dysplasia. Thus, clinical differences between steroid treated and untreated neonates are minimised."



Results indicated that after correcting for lung disease as well as other factors that can contribute to ROP risk such as gestational age, there is still a higher risk of ROP in steroid-treated infants than in those infants not treated with steroids. 1,059 (72%) of the infants received postnatal steroids while 413 (28%) did not. The overall incidence of ROP (of any stage) for the entire group was 76.6%, and the overall incidence of advanced stage ROP (stages 3, 4, or 5) was 31.3%. The incidence of any ROP was significantly higher in steroid-treated infants (80.5%) than in nontreated infants (66.8%). For advanced stage ROP, incidence was also significantly higher in the treated group (35.3%) compared to the untreated group (21.1%).

"This study of a large database of critically low birth weight survivors indicates that steroid-treated infants have a modest but significantly increased risk for ROP. That said, clinicians need to use their best judgment to balance the positive effects from steroids on developing lungs with potential negative effects on developing eyes in very premature infants," commented Dr. Movsas. This study has potential clinical significance since children with a history of ROP are not only at increased risk for visual impairments from the ROP itself, but are also at increased risk for developing other ocular disorders later in life."

SOURCE: Elsevier Health Sciences;

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The unfinished agenda of preterm births


Description: Large image of Figure.

For several years, World Prematurity Day on Nov 17 has highlighted the global efforts to address preterm births. Initiated by the European Foundation for the Care of Newborn Infants (EFCNI), and later joined by the African organisation LittleBigSouls, the US organisation March of Dimes, and the Australian National Premmie Foundation, there are now many initiatives globally that every year shine a spotlight on the plight of preterm infants and their families. An estimated 15 million babies are born before 37 weeks' gestation worldwide and this number is increasing, with rates varying from 5% to 18% of births between countries. In its latest annual report card released on Nov 1, March of Dimes has given the USA a C grade as the rate of preterm births has increased for the first time in 8 years from 9·57% to 9·63%. And even more worryingly, there were widening racial and ethnic inequalities with the rate being 48% higher in black women and 15% higher among American Indian and Alaska Native women than in white women.

Preventing preterm births and caring for preterm infants well to avert mortality and minimise long-term morbidity is now one of the most urgent goals to make further progress in delivering the Sustainable Development Goal target of reducing mortality of children younger than 5 years. In 2015, neonatal disorders caused 45% (or 2·6 million) of under-5 deaths, according to the latest Global Burden of Disease data. Deaths from preterm birth complications became the leading cause of under-5 mortality in 2015. Complicating aspects are that many of the risk factors for preterm birth, such as hypertension, diabetes, and other non-communicable diseases, exposure to air pollution, advanced maternal age, and poor maternal nutrition are increasing not only in high-income countries, but especially in low-income and middle-income countries. And some of the greatest health disparities not only between but also within countries are found in antenatal care, access to contraception and family planning, skilled birth attendance, and post-natal care. Disadvantaged women and girls are at particular risk for premature births for many reasons, ranging from untreated infections and undernutrition to hard labour during pregnancy.

Prevention has to take a lifecourse approach, with preventing teenage pregnancies, improving nutrition and wellbeing of all women of childbearing age, spacing pregnancies, improved pregnancy care including the optimum treatment of chronic diseases and counselling about risk factors such as alcohol and tobacco, and interventions such as antenatal steroids when appropriate. However, not all preterm births will be preventable and neonatal intensive care standards are crucial to improve survival and minimise long-term sequelae. EFCNI has developed the European Standards of Care for Newborn Health initiative—a collaboration of more than 220 health-care professionals, parent representatives, and selected industry specialists from more than 34 countries. The 11 broad areas of standards for neonatal health are: birth and transfer; patient safety and hygiene practice; infant and family centred care; follow-up and continuing care; data collection and documentation; medical care and clinical practice; care procedures; neonatal intensive care unit design; nutrition; ethical decisions; and education and training. Many of these standards, however, are currently far out of reach for low-income and middle-income countries, where the mortality of those born before 28 weeks' gestation remains extremely high.

The continuing progress in the survival of premature infants, at least in high-income countries where now more than 90% of those born at 28 weeks' gestation survive to discharge, raises further questions about the long-term outcomes of those born prematurely. There is evidence that children born prematurely have increased risk of respiratory illnesses and lower achieved lung growth, as well as emerging evidence that they have increased risk of type 2 diabetes, hypertension, and other chronic diseases earlier in adulthood than those born at term. However, much progress in neonatal care is relatively recent with exogenous surfactant only given to those born in the early 1990s.

What is most needed at a global level is the reassurance of the continuing UN commitment to the Every Woman, Every Child agenda and the Global Strategy for Women's, Children's and Adolescents' Health (2016–2030). Only with this broad lifecourse approach firmly rooted in human rights and equity, continuing and accelerated efforts by the many partners already involved, and firm financial support will we tackle the unfinished agenda of preterm births and neonatal mortality. The next UN Secretary-General, Antonio Guterres, must make this one of his top priorities.

(The Lancet; Published: 12 November 2016; DOI:

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Transcutaneous Bilirubin Testing Is Feasible in Neonates


Transcutaneous bilirubinometry (TcB) is feasible and safe for evaluation of jaundiced neonates, researchers report.

"I strongly favor the use of the transcutaneous bilirubinometry, like any non-invasive procedure, over invasive and painful procedures in children, as long as it is safe and effective," Dr. Jolita Berkhof from Amalia Children's Clinic, Zwolle, The Netherlands told Reuters Health by email. "The only drawback is the cost. The device is costly, so poor resource countries might be reluctant to invest in the method."

TcB is a valid method for assessing the severity of jaundice, but it is uncommonly used in sick neonates because blood sampling in these children is often done for other indications and serum bilirubin can be measured simultaneously.

In a randomized trial involving 430 hospitalized jaundiced newborns, Dr. Berkhof and colleagues sought to quantify the reduction in blood draws as a result of implementing TcB from 32 weeks' gestational age, compared with visual assessment with subsequent blood sampling for determination of serum bilirubin.

Use of the Air-Shields Jaundice Meter-103 (Drager Konica Minolta, Lubeck, Germany) was associated with a 38.5% reduction in the number of blood draws per neonate (21.1% of those in the neonatal ward for sick neonates and 44.4% of those in the maternity ward), according to the November 4th Pediatrics online report.

There were no significant differences in secondary outcomes (highest serum bilirubin level, phototherapy, severe serum bilirubin, length of hospitalization, and serum bilirubin value above exchange transfusion threshold) between the TcB and control groups.

There were no cases of clinical kernicterus, and none of the measured serum bilirubin values was extreme (at or above 425 umol/L) or hazardous (at or above 512 umol/L).

In 158 paired samples, TcB bilirubin values were an average 7.0 umol/L higher than the respective serum bilirubin levels, with limits of agreement between -56.9 and 71.0 umol/L.

"We should further investigate if the use of the bilirubinometer can be applied during and after phototherapy as well; this would further reduce the number of blood draws and costs," Dr. Berkhof said.

Dr. Jeffrey Maisels from Beaumont Children's Hospital, Royal Oak, Michigan told Reuters Health, "This study confirms numerous previous observations of the safety and utility of transcutaneous bilirubin measurements in newborn infants and that transcutaneous measurements significantly reduce the number of serum bilirubin measurements required. This is, however, the first randomized controlled trial in a Western population documenting the reduction in serum bilirubin measurements."

"As I've written before, the benefits to infants, parents, and care providers of an instantaneous, noninvasive estimate of the serum bilirubin level, are abundant," Dr. Maisels concluded. "The authors note the benefit of these measurements in hospitalized infants, but even greater benefits could be derived from having these instruments available in every hospital outpatient clinic, every emergency department, and in the office of every pediatrician and family practitioner."

Isala's Foundation for Innovation and Research funded this study. The authors had no financial conflicts to declare. (SOURCE:;  Pediatrics 2016).



-Will Boggs MD In Reuters, November 08, 2016