A study of the cost and effect of newborn screening for Congenital Adrenal Hyperplasia in Texas

Congenital Adrenal Hyperplasia (CAH), due to 21-Hydroxylase deficiency, has an estimated incidence of 1:15,000 births and can result in death, salt-wasting crisis or impaired growth. It has been proposed that early diagnosis and treatment of infants detected from newborn screening for CAH will decrease the incidence of mortality and morbidity in the affected population. The Texas Department of Health (TDH) began mandatory screening for CAH in June, 1989 and Texas is one of fourteen states to provide neonatal screening for the disorder.^ The purpose of this study was to describe the cost and effect of screening for CAH in Texas during 1994 and to compare cases first detected by screen and first detected clinically between January 1, 1990 and December 31, 1994. This study used a longitudinal descriptive research design. The data was secondary and previously collected by the Texas Department of Health. Along with the descriptive study, an economic analysis was done. The cost of the program was defined, measured and valued for four phases of screening: specimen collection, specimen testing, follow-up and diagnostic evaluation.^ There were 103 infants with Classical CAH diagnosed during the study and 71 of the cases had the more serious Salt-Wasting form of the disease. Of the infants diagnosed with Classical CAH, 60% of the cases were first detected by screen and 40% were first detected because of clinical findings before the screening results were returned. The base case cost of adding newborn screening to an existing program (excluding the cost of specimen collection) was $357,989 for 100,000 infants. The cost per case of Classical CAH diagnosed, based on the number of infants first detected by screen in 1994, was \$126,892. There were 42 infants diagnosed with the more benign Nonclassical form of the disease. When these cases were included in the total, the cost per infant to diagnose Congenital Adrenal/Hyperplasia was $87,848. ^

Comparisons of Mortality and Pre-discharge Respiratory Outcomes in Small-for-gestational-age and Appropriate-for-gestational-age Premature Infants.

BACKGROUND: There are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth. OBJECTIVE: To compare mortality and respiratory morbidity of SGA and AGA premature newborn infants. DESIGN/METHODS: A retrospective study was done of the 2,487 infants born without congenital anomalies at RESULTS: Controlling for GA, premature SGA infants were at a higher risk for mortality (Odds ratio 3.1, P = 0.001) and at lower risk of respiratory distress syndrome (OR = 0.71, p = 0.02) than AGA infants. However multivariate logistic regression modeling found that the odds of having respiratory distress syndrome (RDS) varied between SGA and AGA infants by GA. There was no change in RDS risk in SGA infants at GA 32 wk (OR = 0.41, 95% CI 0.27 - 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 - 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26-36 wks GA than AGA infants. CONCLUSIONS: Premature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at >/=32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.

Assessment of the role of LASER-Doppler in the treatment of port-wine stains in infants

BACKGROUND Port-wine stains (PWS) are malformations of capillaries in 0.3% of newborn children. The treatment of choice is by pulsed dye LASER (PDL), and requires several sessions. The efficacy of this treatment is at present evaluated on the basis of clinical inspection and of digital photographs taken throughout the treatment. LASER-Doppler imaging (LDI) is a noninvasive method of imaging the perfusion of the tissues by the microcirculatory system (capillaries). The aim of this paper is to demonstrate that LDI allows a quantitative, numerical evaluation of the efficacy of the PDL treatment of PWS. METHOD The PDL sessions were organized according to the usual scheme, every other month, from September 1, 2012, to September 30, 2013. LDI imaging was performed at the start and at the conclusion of the PDL treatment, and simultaneously on healthy skin in order to obtain reference values. The results evidenced by LDI were analyzed according to the "Wilcoxon signed-rank" test before and after each session, and in the intervals between the three PDL treatment sessions. RESULTS Our prospective study is based on 20 new children. On average, the vascularization of the PWS was reduced by 56% after three laser sessions. Compared with healthy skin, initial vascularization of PWS was 62% higher than that of healthy skin at the start of treatment, and 6% higher after three sessions. During the 2 months between two sessions, vascularization of the capillary network increased by 27%. CONCLUSION This study shows that LDI can demonstrate and measure the efficacy of PDL treatment of PWS in children. The figures obtained when measuring the results by LDI corroborate the clinical assessments and may allow us to refine, and perhaps even modify, our present use of PDL and thus improve the efficacy of the treatment.

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation.

BACKGROUND Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. METHODS Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. RESULTS In fully treated animals (LPS + MV + 60% O(2)) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. CONCLUSION MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in ~30% of preterm infants born less than 30 wk of gestation (1). Its main risk factors include lung immaturity due to preterm delivery, mechanical ventilation (MV), oxygen toxicity, chorioamnionitis, and sepsis. The main feature is an arrest of alveolar and capillary formation (2). Models trying to decipher genes involved in the pathophysiology of BPD are mainly based on MV and oxygen application to young mammals with immature lungs of different species (3). In newborn rodent models, analyses of lung structure and gene and protein expression are performed for practical reasons directly at the end of MV (4,5,6). However, later appearing changes of gene expression might also have an impact on lung development and the evolution towards BPD and cannot be discovered by such models. Recently, we developed a newborn rat model of MV using an atraumatic (orotracheal) intubation technique that allows the weaning of the newborn animal off anesthesia and MV, the extubation to spontaneous breathing, and therefore allows the evaluation of effects of MV after a ventilation-free period of recovery (7). Indeed, applying this concept of atraumatic intubation by direct laryngoscopy, we recently were able to show significant differences between gene expression changes appearing directly after MV compared to those measured after a ventilation-free interval of 48 h. Immediately after MV, inflammation-related genes showed a transitory modified expression, while another set of more structurally related genes changed their expression only after a delay of 2 d (7). Lung structure, analyzed by conventional 2D histology and also by 3D reconstruction using synchrotron x-ray tomographic microscopy revealed, 48 h after end of MV, a reduced complexity of lung architecture compared to the nonventilated rat lungs, similar to the typical findings in BPD. To extend these observations about late gene expression modifications, we performed with a similar model a full gene expression profile of lung tissue 48 h after the end of MV with either room air or 60% oxygen. Essentially, we measured changes in the expression of genes related to the MMPs and complement system which played a role in many of the six identified mostly affected pathways.

Clinical decisions related to CBC screening of asymptomatic full-term infants at risk for group B streptococcus disease

Objective. Although complete blood count (CBC) changes occur with the development of clinical sepsis in newborns, the CBC has not been reported to be a sensitive predictor of sepsis in asymptomatic full-term newborn infants, nor has it been reported to be related to risk factors for sepsis or clinical decisions. The objective of this study was to evaluate the relationship between the WBC/I:T (immature:total neutrophil) ratio and maternal group B streptococcal (GBS) risk factors (rupture of membranes ≥18 hours, maternal temperature ≥100.4°F, maternal age ≤20 years, previous infant with invasive GBS disease, maternal GBS bacteriuria, and black ethnicity); and to evaluate the relationship between the WBC/I:T ratios and providers' clinical decisions (observe versus repeat the CBC or complete sepsis evaluation) in the asymptomatic full-term newborn at risk for early-onset GBS sepsis. ^ Methods. Medical records of infants admitted to the well baby nursery at a tertiary care teaching hospital in Houston, TX between 1/1/99 and 12/31/00 whose gestational ages were ≥35 weeks; who had mothers with GBS positive or unknown culture status and inadequate intrapartum antibiotic prophylaxis; and who had screening CBCs performed in the first 30 hours of life because of GBS risk were reviewed (n = 412). Demographic information, maternal GBS risk factors, CBC results, clinical decisions, and rationales for clinical decisions were collected. ^ Results. With the exception of black ethnicity (p = .0000, odds ratio = 0.213), no statistically significant differences in risk factors between infants with normal and abnormal WBC counts or normal and abnormal I:T ratios were found. Infants with abnormal WBCs had a significantly higher likelihood of having a CBC repeated (p = 0.002 for WBC). Providers documented the CBC result in the rationale for clinical decisions in 62% of the cases. ^ Conclusion. The CBC results were not related to maternal risk factors for GBS except for ethnicity. Black infants had significantly lower WBC levels than infants of other ethnicities, although this difference was clinically insignificant. Infants with abnormal WBCs had a significantly higher likelihood of undergoing repeat CBCs but not sepsis evaluations. Provider rationale was difficult to evaluate due to insufficient documentation. The screening CBC result did not impact the clinicians' decisions to initiate sepsis evaluations in this population. ^

A COMPARISON OF NEONATAL MORTALITY BETWEEN HOSPITALS WITH LEVEL III NEWBORN INTENSIVE CARE UNITS AND ALL OTHER HOUSTON HOSPITALS

A number of medical and social developments have had an impact on the neonatal mortality over the past ten to 15 years in the United States. The purpose of this study was to examine one of these developments, Newborn Intensive Care Units (NICUs), and evaluate their impact on neonatal mortality in Houston, Texas.^ This study was unique in that it used as its data base matched birth and infant death records from two periods of time: 1958-1960 (before NICUs) and 1974-1976 (after NICUs). The neonatal mortality of single, live infants born to Houston resident mothers was compared for two groups: infants born in hospitals which developed NICUs and infants born in all other Houston hospitals. Neonatal mortality comparisons were made using the following birth-characteristic variables: birthweight, gestation, race, sex, maternal age, legitimacy, birth order and prenatal care.^ The results of the study showed that hospitals which developed NICUs had a higher percentage of their population with high risk characteristics. In spite of this, they had lower neonatal mortality rates in two categories: (1) white 3.5-5.5 pounds birthweight infants, (2) low birthweight infants whose mothers received no prenatal care. Black 3.5-5.5 pounds birthweight infants did equally well in either hospital group. While the differences between the two hospital groups for these categories were not statistically significant at the p < 0.05 level, data from the 1958-1960 period substantiate that a marked change occurred in the 3.5-5.5 pounds birthweight category for those infants born in hospitals which developed NICUs. Early data were not available for prenatal care. These findings support the conclusion that, in Houston, NICUs had some impact on neonatal mortality among moderately underweight infants. ^

Biochemical mechanisms involved in pulmonary hypo-alveolarization induced by peroxides contaminating parenteral nutrition in newborn guinea pig

La dysplasie broncho-pulmonaire (DBP), caractérisée par un défaut de l’alvéolarisation, est une complication pathologique associée à un stress oxydant chez le nouveau-né prématuré. La DBP est présente chez près de 50 % des nouveau-nés de moins de 29 semaines de gestation. La nutrition parentérale (NP) que ces nouveau-nés reçoivent pour cause d’immaturité gastro-intestinale est une source importante de stress oxydant. En effet, leur NP est contaminée par des peroxydes, dont l’ascorbylperoxyde qui est une forme peroxydée du déshydroascorbate. La génération des peroxydes est catalysée par la lumière ambiante. La photoprotection de la NP, quoique difficile d’application en clinique, est associée à une diminution de l’incidence de la DBP chez les enfants prématurés. Chez l’animal nouveau-né, la photoprotection de la NP est associée à un meilleur développement alvéolaire. Ainsi, nous émettons l’hypothèse que l’ascorbylperoxide infusé avec la NP cause la perte d’alvéoles suite à une apoptose exagérée induite par l’oxydation du potentiel redox du glutathion. Cette oxydation du potentiel redox serait occasionnée par l’inhibition de la transformation hépatique de la méthionine en cystéine, menant à une diminution de la synthèse de glutathion au foie et dans les tissus tels que les poumons. La confirmation de cette hypothèse suggérera qu’un ajout de glutathion dans la NP permettra une meilleure détoxification de l’ascorbylperoxide par l’action de la glutathion peroxydase, et préviendra l’oxydation du potentiel redox et ainsi, la perte d'alvéoles par apoptose. Objectifs : Le but de mon projet de recherche est de comprendre les mécanismes biochimiques liant la NP et le développement de la DBP chez le nouveau-né prématuré et de proposer une alternative nutritionnelle prévenant le développement de cette complication fréquemment observée dans cette population. Les objectifs spécifiques sont : 1) d’évaluer l’impact, au poumon, de l’infusion de l’ascorbylperoxyde sur l’axe métabolique potentiel redox du glutathion - apoptose - le développement alvéolaire; 2) d’étudier l’impact de l’ascorbylperoxyde et du potentiel redox sur l’activité hépatique de la méthionine adénosyltransférase (MAT), première enzyme de la cascade métabolique transformant la méthionine en cystéine; et 3) de tenter de prévenir l’impact négatif de la NP ou de l’infusion d’ascorbylperoxyde sur le poumon en améliorant le statut en glutathion. Méthodes: Par un cathéter fixé dans la jugulaire, des cochons d’Inde de trois jours de vie (n = 8 par groupe) ont reçu en continu durant 4 jours une NP ou une solution de base (dextrose + NaCl) enrichie des différentes molécules à l’essai. Le premier objectif a été atteint en enrichissant la solution de base en ascorbylperoxyde à 0, 20, 60 et 180 μM. Ces solutions contenaient ou non 350 μM H2O2 pour se rapprocher des conditions cliniques. Le second objectif a été atteint en investiguant les mécanismes d’inhibition de la MAT dans des animaux infusés ou non avec des solutions contenant la solution de base, des peroxydes, du glutathion et la NP (dextrose + acides aminés + multivitamines + lipides). Le troisième objectif a été atteint en ajoutant ou non à une solution d’ascorbylperoxide ou à la NP 10 μM de glutathion (GSSG), afin d’obtenir une concentration plasmatique normale de glutathion. Après 4 jours, les poumons étaient prélevés et traités pour la détermination de GSH et GSSG par électrophorèse capillaire, le potentiel redox était calculé selon l'équation de Nernst et le niveau de caspase-3 actif (marqueur d’apoptose) par Western blot et l’index d’alvéolarisation quantifié par le nombre d’interceptes entre des structures histologiques et une droite calibrée. Les données étaient comparées par ANOVA, les effets étaient considérés comme significatifs si le p était inférieur à 0,05. Résultats: L’infusion de l’ascorbylperoxyde, indépendamment du H2O2, a induit une hypoalvéolarisation, une activation de la caspase-3 et une oxydation du potentiel redox de manière dose-dépendante. Ces effets ont été empêchés par l’ajout de GSSG à la NP ou à la solution d’ascorbylperoxyde (180 M). L’ascorbylperoxyde et le H2O2 ont inhibé l’activité de MAT tandis qu’elle était linéairement modulée par la valeur du potentiel redox hépatique. Conclusion : Nos résultats suggèrent que l’ascorbylperoxyde est l’agent actif de la NP conduisant au développement de la DBP. Ainsi la correction des bas niveaux de glutathion induits par les peroxydes de la NP favorise la détoxification des peroxydes et la correction du potentiel redox pulmonaire ; ce qui a protégé les poumons des effets délétères de la NP en outrepassant l’inhibition de la MAT hépatique. Nos résultats sont d'une grande importance car ils donnent de l'espoir pour une prévention possible de la DBP.

Biochemical mechanisms involved in pulmonary hypo-alveolarization induced by peroxides contaminating parenteral nutrition in newborn guinea pig

La dysplasie broncho-pulmonaire (DBP), caractérisée par un défaut de l’alvéolarisation, est une complication pathologique associée à un stress oxydant chez le nouveau-né prématuré. La DBP est présente chez près de 50 % des nouveau-nés de moins de 29 semaines de gestation. La nutrition parentérale (NP) que ces nouveau-nés reçoivent pour cause d’immaturité gastro-intestinale est une source importante de stress oxydant. En effet, leur NP est contaminée par des peroxydes, dont l’ascorbylperoxyde qui est une forme peroxydée du déshydroascorbate. La génération des peroxydes est catalysée par la lumière ambiante. La photoprotection de la NP, quoique difficile d’application en clinique, est associée à une diminution de l’incidence de la DBP chez les enfants prématurés. Chez l’animal nouveau-né, la photoprotection de la NP est associée à un meilleur développement alvéolaire. Ainsi, nous émettons l’hypothèse que l’ascorbylperoxide infusé avec la NP cause la perte d’alvéoles suite à une apoptose exagérée induite par l’oxydation du potentiel redox du glutathion. Cette oxydation du potentiel redox serait occasionnée par l’inhibition de la transformation hépatique de la méthionine en cystéine, menant à une diminution de la synthèse de glutathion au foie et dans les tissus tels que les poumons. La confirmation de cette hypothèse suggérera qu’un ajout de glutathion dans la NP permettra une meilleure détoxification de l’ascorbylperoxide par l’action de la glutathion peroxydase, et préviendra l’oxydation du potentiel redox et ainsi, la perte d'alvéoles par apoptose. Objectifs : Le but de mon projet de recherche est de comprendre les mécanismes biochimiques liant la NP et le développement de la DBP chez le nouveau-né prématuré et de proposer une alternative nutritionnelle prévenant le développement de cette complication fréquemment observée dans cette population. Les objectifs spécifiques sont : 1) d’évaluer l’impact, au poumon, de l’infusion de l’ascorbylperoxyde sur l’axe métabolique potentiel redox du glutathion - apoptose - le développement alvéolaire; 2) d’étudier l’impact de l’ascorbylperoxyde et du potentiel redox sur l’activité hépatique de la méthionine adénosyltransférase (MAT), première enzyme de la cascade métabolique transformant la méthionine en cystéine; et 3) de tenter de prévenir l’impact négatif de la NP ou de l’infusion d’ascorbylperoxyde sur le poumon en améliorant le statut en glutathion. Méthodes: Par un cathéter fixé dans la jugulaire, des cochons d’Inde de trois jours de vie (n = 8 par groupe) ont reçu en continu durant 4 jours une NP ou une solution de base (dextrose + NaCl) enrichie des différentes molécules à l’essai. Le premier objectif a été atteint en enrichissant la solution de base en ascorbylperoxyde à 0, 20, 60 et 180 μM. Ces solutions contenaient ou non 350 μM H2O2 pour se rapprocher des conditions cliniques. Le second objectif a été atteint en investiguant les mécanismes d’inhibition de la MAT dans des animaux infusés ou non avec des solutions contenant la solution de base, des peroxydes, du glutathion et la NP (dextrose + acides aminés + multivitamines + lipides). Le troisième objectif a été atteint en ajoutant ou non à une solution d’ascorbylperoxide ou à la NP 10 μM de glutathion (GSSG), afin d’obtenir une concentration plasmatique normale de glutathion. Après 4 jours, les poumons étaient prélevés et traités pour la détermination de GSH et GSSG par électrophorèse capillaire, le potentiel redox était calculé selon l'équation de Nernst et le niveau de caspase-3 actif (marqueur d’apoptose) par Western blot et l’index d’alvéolarisation quantifié par le nombre d’interceptes entre des structures histologiques et une droite calibrée. Les données étaient comparées par ANOVA, les effets étaient considérés comme significatifs si le p était inférieur à 0,05. Résultats: L’infusion de l’ascorbylperoxyde, indépendamment du H2O2, a induit une hypoalvéolarisation, une activation de la caspase-3 et une oxydation du potentiel redox de manière dose-dépendante. Ces effets ont été empêchés par l’ajout de GSSG à la NP ou à la solution d’ascorbylperoxyde (180 M). L’ascorbylperoxyde et le H2O2 ont inhibé l’activité de MAT tandis qu’elle était linéairement modulée par la valeur du potentiel redox hépatique. Conclusion : Nos résultats suggèrent que l’ascorbylperoxyde est l’agent actif de la NP conduisant au développement de la DBP. Ainsi la correction des bas niveaux de glutathion induits par les peroxydes de la NP favorise la détoxification des peroxydes et la correction du potentiel redox pulmonaire ; ce qui a protégé les poumons des effets délétères de la NP en outrepassant l’inhibition de la MAT hépatique. Nos résultats sont d'une grande importance car ils donnent de l'espoir pour une prévention possible de la DBP.

Implementing universal newborn hearing screening programs : early identification of hearing loss.

Shipping list no.: 99-0282-P.

Missing links : coordinating federal drug policy for women, infants, and children : hearing before the Committee on Governmental Affairs, United States Senate, One Hundred First Congress, first session, July 31, 1989.

Shipping list no.: 90-200-P.

Universal newborn hearing screening in Illinois, 2003-2004 /

"This publication was supported in part by Grant/Cooperative Agreement US50/CCU523303-04 and Early Hearing Detection and Intervention Award UR#CC1520048 from the U.S. Centers for Disease Control and Prevention. ..."--Leaf ii.

Skin exposure during conventional phototherapy in preterm infants: A randomized controlled trial

Objective: To assess the effect of reduced skin exposure in preterm infants receiving overhead phototherapy treatment on total serum bilirubin (TSB). Methods: Randomized controlled trial. Preterm infants (>1500 g birthweight and less than or equal to 36 weeks gestation) were randomized to being nursed either partially clothed with only disposable nappies and in posturally supported positions (n = 30) or naked without postural support (n = 29). Primary outcome was mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment (irradiance of 6 muWcm(-2)/nm at a wavelength of 425-475 nm). The incidence of rebound jaundice, number of infants continuing to receive phototherapy treatment at 24 h periods, parental stress, mother-infant interaction and mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment were examined. Results: Mean TSB percentage change at 24 h of completed treatment for the partially clothed group was 15.4% (+/-18) and for the naked group 19% (+/-15) (mean difference 3.6% 95% CI -5.1, 12.3). No other outcomes were significantly affected by reduced skin exposure to overhead phototherapy treatment. Conclusion: Our results show no statistically significant difference in TSB level change using either nursing practice.

Monitoring Infants By Automatic Video Processing

This work has, as its objective, the development of non-invasive and low-cost systems for monitoring and automatic diagnosing specific neonatal diseases by means of the analysis of suitable video signals. We focus on monitoring infants potentially at risk of diseases characterized by the presence or absence of rhythmic movements of one or more body parts. Seizures and respiratory diseases are specifically considered, but the approach is general. Seizures are defined as sudden neurological and behavioural alterations. They are age-dependent phenomena and the most common sign of central nervous system dysfunction. Neonatal seizures have onset within the 28th day of life in newborns at term and within the 44th week of conceptional age in preterm infants. Their main causes are hypoxic-ischaemic encephalopathy, intracranial haemorrhage, and sepsis. Studies indicate an incidence rate of neonatal seizures of 0.2% live births, 1.1% for preterm neonates, and 1.3% for infants weighing less than 2500 g at birth. Neonatal seizures can be classified into four main categories: clonic, tonic, myoclonic, and subtle. Seizures in newborns have to be promptly and accurately recognized in order to establish timely treatments that could avoid an increase of the underlying brain damage. Respiratory diseases related to the occurrence of apnoea episodes may be caused by cerebrovascular events. Among the wide range of causes of apnoea, besides seizures, a relevant one is Congenital Central Hypoventilation Syndrome (CCHS) \cite{Healy}. With a reported prevalence of 1 in 200,000 live births, CCHS, formerly known as Ondine's curse, is a rare life-threatening disorder characterized by a failure of the automatic control of breathing, caused by mutations in a gene classified as PHOX2B. CCHS manifests itself, in the neonatal period, with episodes of cyanosis or apnoea, especially during quiet sleep. The reported mortality rates range from 8% to 38% of newborn with genetically confirmed CCHS. Nowadays, CCHS is considered a disorder of autonomic regulation, with related risk of sudden infant death syndrome (SIDS). Currently, the standard method of diagnosis, for both diseases, is based on polysomnography, a set of sensors such as ElectroEncephaloGram (EEG) sensors, ElectroMyoGraphy (EMG) sensors, ElectroCardioGraphy (ECG) sensors, elastic belt sensors, pulse-oximeter and nasal flow-meters. This monitoring system is very expensive, time-consuming, moderately invasive and requires particularly skilled medical personnel, not always available in a Neonatal Intensive Care Unit (NICU). Therefore, automatic, real-time and non-invasive monitoring equipments able to reliably recognize these diseases would be of significant value in the NICU. A very appealing monitoring tool to automatically detect neonatal seizures or breathing disorders may be based on acquiring, through a network of sensors, e.g., a set of video cameras, the movements of the newborn's body (e.g., limbs, chest) and properly processing the relevant signals. An automatic multi-sensor system could be used to permanently monitor every patient in the NICU or specific patients at home. Furthermore, a wire-free technique may be more user-friendly and highly desirable when used with infants, in particular with newborns. This work has focused on a reliable method to estimate the periodicity in pathological movements based on the use of the Maximum Likelihood (ML) criterion. In particular, average differential luminance signals from multiple Red, Green and Blue (RGB) cameras or depth-sensor devices are extracted and the presence or absence of a significant periodicity is analysed in order to detect possible pathological conditions. The efficacy of this monitoring system has been measured on the basis of video recordings provided by the Department of Neurosciences of the University of Parma. Concerning clonic seizures, a kinematic analysis was performed to establish a relationship between neonatal seizures and human inborn pattern of quadrupedal locomotion. Moreover, we have decided to realize simulators able to replicate the symptomatic movements characteristic of the diseases under consideration. The reasons is, essentially, the opportunity to have, at any time, a 'subject' on which to test the continuously evolving detection algorithms. Finally, we have developed a smartphone App, called 'Smartphone based contactless epilepsy detector' (SmartCED), able to detect neonatal clonic seizures and warn the user about the occurrence in real-time.

Oxygen targeting in preterm infants using the Masimo SET Radical pulse oximeter

BACKGROUND: A pretrial clinical improvement project for the BOOST-II UK trial of oxygen saturation targeting revealed an artefact affecting saturation profiles obtained from the Masimo Set Radical pulse oximeter.

METHODS: Saturation was recorded every 10 s for up to 2 weeks in 176 oxygen dependent preterm infants in 35 UK and Irish neonatal units between August 2006 and April 2009 using Masimo SET Radical pulse oximeters. Frequency distributions of % time at each saturation were plotted. An artefact affecting the saturation distribution was found to be attributable to the oximeter's internal calibration algorithm. Revised software was installed and saturation distributions obtained were compared with four other current oximeters in paired studies.

RESULTS: There was a reduction in saturation values of 87-90%. Values above 87% were elevated by up to 2%, giving a relative excess of higher values. The software revision eliminated this, improving the distribution of saturation values. In paired comparisons with four current commercially available oximeters, Masimo oximeters with the revised software returned similar saturation distributions.

CONCLUSIONS: A characteristic of the software algorithm reduces the frequency of saturations of 87-90% and increases the frequency of higher values returned by the Masimo SET Radical pulse oximeter. This effect, which remains within the recommended standards for accuracy, is removed by installing revised software (board firmware V4.8 or higher). Because this observation is likely to influence oxygen targeting, it should be considered in the analysis of the oxygen trial results to maximise their generalisability.

Agreement of Mixed Venous Carbon Dioxide Tension (PvCO2) and Transcutaneous Carbon Dioxide (PtCO2) Measurements in Ventilated Infants

Background: Noninvasive transcutaneous carbon dioxide monitoring has been shown to be accurate in infants and children, limited data are available to show the usefulness and limitations of partial transcutaneous carbon dioxide tension (PtCO2) value. Objectives: The current study prospectively determines the effectiveness and accuracy of PtCO2 measurements in newborns. Materials and Methods: Venous blood gas sampling and monitoring of the PtCO2 level (TCM TOSCA, Radiometer) were done simultaneously. All measurements are performed on mechanically ventilated infants. Partial venous carbon dioxide tension (PvCO2) values divided into three groups according to hypocapnia (Group 1: < 4.68 kPa), normocapnia (Group 2: 4.68–7.33 kPa), hypercapnia (Group 3: > 7.33 kPa) and then PvCO2 and PtCO2 data within each group were compared separately. Results: A total of 168 measurements of each PvCO2 and PtCO2 data were compared in three separated groups simultaneously (13 in Group 1, 118 in Group 2, and 37 in Group 3). A bias of more than ± 0.7 kPa was considered unacceptable. PtCO2 was related to PvCO2 with acceptable results between the two measurements in hypocapnia (mean difference 0.20 ± 0.19 kPa) and normocapnia (0.002 ± 0.30 kPa) groups. On the other hand in hypercapnia group PtCO2 values were statistically significant (P < 0.001) and lower than PvCO2 data (mean difference 0.81 ± 1.19 kPa) Conclusions: PtCO2 measurements have generally good agreement with PvCO2 in hypocapnic and normocapnic intubated infants but there are some limitations especially with high level of CO2 tension. Monitoring of PtCO2 is generally a useful non-invasive indicator of PvCO2 in hypocapnic and normocapnic infants.