[Show abstract][Hide abstract] ABSTRACT: Background:
Preterm birth is the leading cause of child death worldwide. Small and sick newborns require timely, high-quality inpatient care to survive. This includes provision of warmth, feeding support, safe oxygen therapy and effective phototherapy with prevention and treatment of infections. Inpatient care for newborns requires dedicated ward space, staffed by health workers with specialist training and skills. Many of the estimated 2.8 million newborns that die every year do not have access to such specialised care.
The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks" (or factors that hinder the scale up) of maternal-newborn intervention packages. For this paper, we used quantitative and qualitative methods to analyse the bottleneck data, and combined these with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for inpatient care of small and sick newborns.
Inpatient care of small and sick newborns is an intervention package highlighted by all country workshop participants as having critical health system challenges. Health system building blocks with the highest graded (significant or major) bottlenecks were health workforce (10 out of 12 countries) and health financing (10 out of 12 countries), followed by community ownership and partnership (9 out of 12 countries). Priority actions based on solution themes for these bottlenecks are discussed.
Whilst major bottlenecks to the scale-up of quality inpatient newborn care are present, effective solutions exist. For all countries included, there is a critical need for a neonatal nursing cadre. Small and sick newborns require increased, sustained funding with specific insurance schemes to cover inpatient care and avoid catastrophic out-of-pocket payments. Core competencies, by level of care, should be defined for monitoring of newborn inpatient care, as with emergency obstetric care. Rather than fatalism that small and sick newborns will die, community interventions need to create demand for accessible, high-quality, family-centred inpatient care, including kangaroo mother care, so that every newborn can survive and thrive.
[Show abstract][Hide abstract] ABSTRACT: Neonatal screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in any population with a male frequency >3-5%, combined with parental education regarding the dietary, environmental and sepsis-related triggers for hemolysis was recommended by the WHO (World Health Organization) Working Group in 1989. As the aim of identifying G-6-PD deficiency in the newborn period is to avert or detect extreme hyperbilirubinemia developing at home, before the development of kernicterus, the parental role in identifying evolving icterus was considered integral to any screening program. Now, a quarter century after publication of this report, severe bilirubin neurotoxicity associated with G-6-PD deficiency continues to be encountered worldwide. Screening programs have not been universally introduced but several national or regional maternal child health programs have implemented neonatal G-6-PD screening. Some reports detail the role of parental education, based on the above mentioned principles, through a variety of audio-visual materials. The paucity of randomized controlled trials or validated evidence to demonstrate the effectiveness of the contribution of parental education fails to meet the ideal testable evidence-based approach. However, our review of the cumulative experience and evidence currently available does supply certain information reflecting a positive impact of screening programs combined with parental input. We propose that the current information is sufficient to continue to support and apply the Working Group's recommendations. In order not to waste unnecessary time available, data may be used in lieu of randomized trials to continue to recommend screening programs, as suggested, in high-risk regions. If the incidence of kernicterus associated with G-6-PD deficiency is to be diminished, G-6-PD screening in combination with parental explanation may be one instance in which the consensus approach suggested by the WHO Working Group, rather than reliance on (nonexistent) evidence-based studies, should continue to be practiced.Journal of Perinatology advance online publication, 16 July 2015; doi:10.1038/jp.2015.77.
Journal of perinatology: official journal of the California Perinatal Association 07/2015; 35(10). DOI:10.1038/jp.2015.77 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the relative contributions of increased bilirubin production (indexed by end-tidal carbon monoxide (CO) concentrations, corrected for ambient CO (ETCOc)) to hour-specific total bilirubin (TB) levels in healthy late preterm and term newborns.
Post hoc analyses of concurrent ETCOc and TB (at 30±6 h of age) and follow-up TB levels at age 96±12 h and up to 168 h after birth were performed in a cohort of 641 term and late preterm infants.
Increased bilirubin production (hour-specific ETCOc ⩾1.7 p.p.m. at age 30±6 h) was noted in ~80%, 42% and 32% of infants in the high-, intermediate- and low-risk TB zones, respectively. One infant with TB <40th percentile and ETCOc <1.7 p.p.m. developed TB ⩾95th percentile at age 168 h, probably due to decreased bilirubin elimination.
Infants in the high-risk quartile of the hour-specific bilirubin nomogram have a higher mean bilirubin production. Infants with TB levels ⩾95th percentile without increased bilirubin production have impaired bilirubin elimination.Journal of Perinatology advance online publication, 16 April 2015; doi:10.1038/jp.2015.32.
Journal of perinatology: official journal of the California Perinatal Association 04/2015; 35(9). DOI:10.1038/jp.2015.32 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: External thermal support is critical for preterm or ill infants due to altered thermoregulation. Incubators are the gold standard for long-term support and have been adopted successfully in many countries. Alternatives such as radiant warmers, blankets and others are often used as standard of care (SoC) in resource-limited settings when infants are otherwise not in Kangaroo Mother Care (KMC).
In this pilot study, we evaluate the feasibility of a conductive thermal mattress (CTM) using phase change materials as a low-cost warmer. We conducted a prospective multicentre open-label randomised controlled trial to determine non-inferiority of this CTM to SoC warming practices in low birthweight infants. The primary outcome was maintenance of axillary temperature.
We equally randomised 160 infants to CTM or SoC. The latter cohort continued to receive warmth by radiant warmers (n=48), blankets (n=18), warmed cradles (n=7) or KMC (n=7) before, during and subsequent to the study. CTM was deemed non-inferior since warmed babies had higher axillary temperature compared with SoC (mean increase 0.11±0.03°C SEM; p<0.001). Post hoc comparison to radiant warmers alone showed that CTM led to a higher axillary temperature (mean increase by 0.14±0.03°C SEM; p<0.001).
Short-term use of CTM compared with radiant warmers and other modes of warming is non-inferior to SoC and efficacious in maintaining body temperature. No adverse effects were reported. An extended multinational trial, preferably one that demonstrates longer-term thermoregulation, is warranted.
Clinical Trials Registry of India (CTRI/2010/091/002916 and CTRI/2011/04/001696).
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Archives of Disease in Childhood - Fetal and Neonatal Edition 03/2015; 100(4). DOI:10.1136/archdischild-2014-306269 · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated levels of end-tidal carbon monoxide corrected for inhaled carbon monoxide (ETCOc), have been correlated with blood carboxyhemoglobin corrected for inhaled carbon monoxide (COHbc) and increased bilirubin production in both healthy newborn infants and those with haemolysis. Elevated bilirubin production has also been reported in infants born premature, born to mothers with diabetes, with bruising or birth trauma, with iso-immune haemolytic disorders, such as maternal-fetal blood group incompatibilities with ABO, Rh, or other minor groups, glucose-6-phosphate dehydrogenase (G6PD) deficiency, structural and functional red blood cell abnormalities and perinatal sepsis (1-6). The 2004 American Academy of Pediatrics (AAP) guideline (7) specifically recommends that ETCOc measurements be used to identify the presence of haemolysis in infants and their subsequent risk for hyperbilirubinemia based on observations that heme degradation from senescing red blood cells leads to the equimolar production of carbon monoxide (CO) and bilirubin in the absence of exposure to high ambient CO or active tissue injury (8).This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND
Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin levels because albumin binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors.METHODS
We utilized a novel modification of a previously-developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubin-induced neurotoxicity.RESULTSTB and BBC levels ranged from 0.7-22.8 and 6.3-47.5mg/dL, respectively. GA correlated with BBC (r=0.54, P <0.0002) with a slope of 0.93mg/dL/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45% and 67% saturation of our observed regression line, respectively.CONCLUSION
We speculate that the spread of BBC levels around the regression line (±5.8mg/dL) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared to TB and GA.Pediatric Research (2014); doi:10.1038/pr.2014.191.
Pediatric Research 11/2014; 77(2). DOI:10.1038/pr.2014.191 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Central apnea, defined as cessation of breathing for ≥20s, is frequent in premature infants born at <34 weeks׳ gestation but uncommon among healthy late preterm (34(0/7)-36(6/7) weeks׳ gestation) and term (≥37 weeks׳ gestation) infants, where it is usually a clinical manifestation of a neurological or metabolic problem. There is growing evidence that marked unconjugated hyperbilirubinemia is associated with central apnea in neonates. This article explores the reported association between acute bilirubin encephalopathy and symptomatic apneic events in newborns and the possible mechanisms involved in the pathogenesis of this phenomenon. The prevalence of symptomatic apneic events in reports of acute bilirubin encephalopathy suggests this clinical finding should be considered a sign of bilirubin neurotoxicity.
Seminars in Perinatology 09/2014; 38(7). DOI:10.1053/j.semperi.2014.08.003 · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extreme hyperbilirubinemia (EHB) caused by neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency is strongly associated with mortality and long-term neurodevelopmental impairment, yet there are limited national strategies to reduce this burden in South Asia. Current known and predicted prevalence of G6PD deficiency in Afghanistan, Bangladesh, Bhutan, India, Nepal, and Pakistan ranges from 3.8 to 15 %, with regional "hot spots" exceeding 22 %. Annually, 3.14 million infants are born at risk for this condition. In 2010, South Asian countries reported 37 million (27 %) of world-wide livebirths ≥ 32 wk gestational-age and G6PD deficiency accounted for > 33 % of the global EHB burden, in contrast to 2.2 % for those born in high-income nations. Traditional national approach includes universal newborn screening in malaria-endemic countries or those with prevalence >3.5 %. However, screening implementation should be best optimized using timely quantitative enzyme assay and identification of at-risk female newborns. Furthermore, economic and social constraints, in context of sub-regional variances, call for flexible problem-solving methods in anticipation of changing community demographics. Thus, incremental and need-based newborn screening programs could be the most optimal approach. A human-centered design (HCD) approach, as an alternate pathway, could build the evidence to translate the complex biology of G6PD deficiency and the biodesign of affordable technologies, allowing facilitation of access to knowledge and services, in order to deliver on a long-term public health mandate. Key steps would encompass the initiation of local inquiry of both quantitative and qualitative data to identify at-risk communities and to prospectively design for local innovative solutions.
The Indian Journal of Pediatrics 04/2014; 81(6). DOI:10.1007/s12098-014-1410-y · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Moderate preterm infants remain at increased risk for adverse outcomes, including acute bilirubin encephalopathy (ABE). Evidence-based guidelines for management of hyperbilirubinemia in preterm infants less than 35 weeks' gestational age are not yet optimized. High concentrations of unconjugated bilirubin can cause permanent posticteric neurologic sequelae (kernicterus). Clinical manifestations of ABE in preterm infants are similar to, but often more subtle than, those of term infants. This review outlines clinical strategies to operationalize management of hyperbilirubinemia in moderately preterm infants to meet recently published consensus-based recommendations.
Clinics in perinatology 12/2013; 40(4):679-88. DOI:10.1016/j.clp.2013.07.007 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.
Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.
Twenty-four million (18% of 134 million live births ≥32 wk gestational age from 184 countries; uncertainty range: 23–26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800–477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000–131,000), with a 24% risk for death (114,100; uncertainty range: 59,700–172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.
Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.
[Show abstract][Hide abstract] ABSTRACT: This study investigated the effectiveness of simple-to-implement adjustments of phototherapy devices on irradiance levels in a cross-section of Nigerian hospitals. A total of 76 phototherapy devices were evaluated in 16 hospitals while adjustments were implemented for a subset of 25 devices for which consent was obtained. The mean irradiance level was 7.6 ± 5.9 µW/cm(2)/nm for all devices prior to adjustments. The average irradiance level improved from 9.0 µW/cm(2)/nm to 27.3 µW/cm(2)/nm for the adjusted group (n = 25) compared with 6.8 ± 5.4 µW/cm(2)/nm for the unadjusted group (n = 51). Simple, inexpensive adjustments to phototherapy devices with sub-optimal irradiance levels can significantly improve their effectiveness to acceptable international standards and should be widely promoted in resource-constrained settings.
[Show abstract][Hide abstract] ABSTRACT: Background:
The therapeutic phototherapy action spectrum ranges from 420 to 500 nm. However, a recent report of improved efficacy of fluorescent "turquoise" light (~490 nm) as compared with blue light (~450 nm) underscores the need to define an optimal action spectrum for precision-targeted phototherapy using very narrow wavelength ranges.
We used a current semi-empirical model of the optical properties of skin for robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin (Hb), melanin, and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra" were assembled from the calculated values.
All the calculated action spectra displayed a peak between 472 and 480 nm (most at 476 nm), which is a significant shift from the well-reported 460 nm absorption peak of bilirubin. Of note, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit (Hct).
We speculate that a narrow range of light at 476 nm would be 60% more effective than blue (broadband) fluorescent lamps. Because Hb serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the Hct. A high Hct could reduce therapeutic efficiency.
Pediatric Research 04/2013; 74(1). DOI:10.1038/pr.2013.67 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% in babies <30, 31-32, and 33-34 wks gestational age, respectively. Phototherapy initiated at 24±12 hr effectively prevented hyperbilirubinemia in infants <2,000 g even in the presence of hemolysis. This approach (in 1985) reduced exchange transfusions from 23.9% to 4.8%. Now with 3 decades of experience in implementing effective phototherapy, the need for exchange transfusions has virtually been eliminated. However, bilirubin neurotoxicity continues to be associated with prematurity alone. The ability to better predict this risk, other than birthweight and gestation, has been elusive. Objective tests such as total bilirubin, unbound or free bilirubin, albumin levels, and albumin-bilirubin binding, together with observations of concurrent hemolysis, sepsis, and rapid rate of bilirubin rise have been considered, but their individual or combined predictive utility has yet to be refined. The disruptive effects of immaturity, concurrent neonatal disease, cholestasis, use of total parenteral nutrition or drugs that alter bilirubin-binding abilities augment the clinical risk of neurotoxicity. Current management options rely on the "fine-tuning" of each infant's exposure to beneficial antioxidants and avoidance of silent neurotoxic properties of bilirubin navigated within the safe spectrum of operational thresholds demarcated by experts.
[Show abstract][Hide abstract] ABSTRACT: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked enzymopathy can lead to severe hyperbilirubinemia, acute bilirubin encephalopathy and kernicterus in the United States. Neonatal testing for G6PD deficiency is not yet routine and the American Academy of Pediatrics recommends testing only in jaundiced newborns who are receiving phototherapy whose family history, ethnicity, or geographic origin suggest risk for the condition, or for infants whose response to phototherapy is poor. Screening tests for G6PD deficiency are available, are suitable for use in newborns and have been used in birth hospitals. However, US birth hospitals experience is limited and no national consensus has emerged regarding the need for newborn G6PD testing, its effectiveness or the best approach. Our review of current state of G6PD deficiency screening highlights research gaps and informs specific operational challenges to implement universal newborn G6PD testing concurrent to bilirubin screening in the United States.Journal of Perinatology advance online publication, 21 February 2013; doi:10.1038/jp.2013.14.
Journal of perinatology: official journal of the California Perinatal Association 02/2013; 33(7). DOI:10.1038/jp.2013.14 · 2.07 Impact Factor