Development of the premature infant nose throat-model (PrINT-Model): an upper airway replica of a premature neonate for the study of aerosol delivery

Clinical efficacy of aerosol therapy in premature newborns depends on the efficiency of delivery of aerosolized drug to the bronchial tree. To study the influence of various anatomical, physical, and physiological factors on aerosol delivery in preterm newborns, it is crucial to have appropriate in vitro models, which are currently not available. We therefore constructed the premature infant nose throat-model (PrINT-Model), an upper airway model corresponding to a premature infant of 32-wk gestational age by three-dimensional (3D) reconstruction of a three-planar magnetic resonance imaging scan and subsequent 3D-printing. Validation was realized by visual comparison and comparison of total airway volume. To study the feasibility of measuring aerosol deposition, budesonide was aerosolized through the cast and lung dose was expressed as percentage of nominal dose. The airway volumes of the initial magnetic resonance imaging and validation computed tomography scan showed a relative deviation of 0.94%. Lung dose at low flow (1 L/min) was 61.84% and 9.00% at high flow (10 L/min), p < 0.0001. 3D-reconstruction provided an anatomically accurate surrogate of the upper airways of a 32-wk-old premature infant, making the model suitable for future in vitro testing.

Developmental changes in pain expression in premature, full-term, two- and four-month-old infants

The purpose of this study was to examine the behavioural responses of infants to pain stimuli across different developmental ages. Eighty infants were included in this cross-sectional design. Four subsamples of 20 infants each included: (1) premature infants between 32 and 34 weeks gestational age undergoing heel-stick procedure; (2) full-term infants receiving intramuscular vitamin K injection; (3) 2-month-old infants receiving subcutaneous injection for immunisation against DPT; and (4) 4-month-old infants receiving subcutaneous injection for immunisation against DPT. Audio and video recordings were made for 15 sec from stimulus. Cry analysis was conducted on the first full expiratory cry by FFT with time and frequency measures. Facial action was coded using the Neonatal Facial Action Coding System (NFCS). Results from multivariate analysis showed that premature infants were different from older infants, that full-term newborns were different from others, but that 2- and 4-month-olds were similar. The specific variables contributing to the significance were higher pitched cries and more horizontal mouth stretch in the premature group and more taut tongue in the full-term newborns. The results imply that the premature infant has the basis for communicating pain via facial actions but that these are not well developed. The full-term newborn is better equipped to interact with his caretakers and express his distress through specific facial actions. The cries of the premature infant, however, have more of the characteristics that are arousing to the listener which serve to alert the caregiver of the state of distress from pain.

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Growth and developmental outcomes of the extremely preterm infant

Objetive: To provide information for pediatricians and neonatologists to create realistic outcome expectations and thus help plan their actions. Sources of data: Searches were made of the Cochrane Library, MEDLINE, and Lilacs databases. Summary of the findings: The assessment of growth and development over the first 2-3 years must adjust chronological age with respect of the degree of prematurity. There is special concern regarding the prognoses of small for gestational age preterm infants, and for those with bronchopulmonary dysplasia. Attention must be directed towards improving the nutrition of extremely low birth weight infants during their first years of life; these infants have high prevalence levels of failure to catch-up on growth, diseases and rehospitalizations during their first 2 years. They are frequently underweight and shorter than expected during early childhood, but delayed catch-up growth may occur between 8 and 14 years. Extremely low birth weight infants are at increased risk of neurological abnormalities and developmental delays during their first years of life. Educational, psychological, and behavioral problems are frequent during school years. Teenage and adult outcomes show that although some performance differences persist, social integration is not impaired. Conclusions: The growth and neurodevelopment of all ELBW infants must be carefully monitored after discharge, to ensure that children and their families receive adequate support and intervention to optimize prognoses. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Congenital diaphragmatic hernia in the preterm infant.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns. With advances in neonatal critical care and ventilation strategies, survival in the term infant now exceeds 80% in some centers. Although prematurity is a significant risk factor for morbidity and mortality in most neonatal diseases, its associated risk with infants with CDH has been described poorly. We sought to determine the impact of prematurity on survival using data from the Congenital Diaphragmatic Hernia Registry (CDHR). METHODS: Prospectively collected data from live-born infants with CDH were analyzed from the CDHR from January 1995 to July 2009. Preterm infants were defined as <37 weeks estimated gestational age at birth. Univariate and multivariate logistic regression analysis were>performed. RESULTS: During the study period, 5,069 infants with CDH were entered in the registry. Of the 5,022 infants with gestational age data, there were 3,895 term infants (77.6%) and 1,127 preterm infants (22.4%). Overall survival was 68.7%. A higher percentage of term infants were treated with extracorporeal membrane oxygenation (ECMO) (33% term vs 25.6% preterm). Preterm infants had a greater percentage of chromosomal abnormalities (4% term vs 8.1% preterm) and major cardiac anomalies (6.1% term vs 11.8% preterm). Also, a significantly higher percentage of term infants had repair of the hernia (86.3% term vs 69.4% preterm). Survival for infants that underwent repair was high in both groups (84.6% term vs 77.2% preterm). Survival decreased with decreasing gestational age (73.1% term vs 53.5% preterm). The odds ratio (OR) for death among preterm infants adjusted for patch repair, ECMO, chromosomal abnormalities, and major cardiac anomalies was OR 1.68 (95% confidence interval [CI], 1.34-2.11). CONCLUSION: Although outcomes for preterm infants are clearly worse than in the term infant, more than 50% of preterm infants still survived. Preterm infants with CDH remain a high-risk group. Although ECMO may be of limited value in the extremely premature infant with CDH, most preterm infants that live to undergo repair will survive. Prematurity should not be an independent factor in the treatment strategies of infants with CDH.

The Effects of Instrumental Touching on Infant Pain Perception and the Effects of Eutectic Mixture of Local Anesthetics (EMLA) on the Reduction of Pain

Background: Premature infants, who have to spend the first week of their lives in neonatal intensive care units (NICUs), experience pain and stress in numerous cases, and they are exposed to many invasive interventions. The studies have shown that uncontrolled pain experienced during early life has negative and long-term side effects, such as distress, and such experiences negatively affect the development of the central nervous system Objectives: The purpose of the study was to examine the effects of touching on infant pain perception and the effects of eutectic mixture of local anesthetic (EMLA) on the reduction of pain. Patients and Methods: Data for the study were collected between March and August 2012 from the neonatal clinic of a university hospital located in eastern Turkey. The population of the study consisted of premature infants who were undergoing treatment, completed the first month and who were approved for Hepatitis B vaccine. The study consisted of two experimental groups and one control group. Information forms, intervention follow-up forms, and Premature Infant Pain Profile (PIPP) were used to collect the data. EMLA cream was applied on the vastus lateralis muscles of the first experimental group before the vaccination. The second experimental group was vaccinated by imitation (placebo), without a needle tip or medicine. Vaccination was carried out using instrumental touch in this group. A routine vaccination was applied in the control group. Results: Mean pain scores of the group to which EMLA was applied were lower in a statistically significant way (P < 0.05) compared to the pain scores of the other groups. Moreover, it was determined that even though invasive intervention was not applied to the newborns, the touching caused them to feel pain just as in the placebo group (P < 0.005). Conclusions: The results demonstrated that EMLA was an effective method for reducing pain in premature newborns, and the use of instrumental touch for invasive intervention stimulated the pain perception in the newborns.

Parents' perceptions of microneedle-mediated monitoring as an alternative to blood sampling in the monitoring of their infants

OBJECTIVES: Microneedle (MN) arrays could offer a pain-free, minimally invasive approach to monitoring. This is envisaged to be particularly beneficial for younger patients, but parents' views to date are unknown. The aim of this study was to explore parental perceptions of MN-mediated ISF monitoring, as an alternative to the use of conventional blood sampling, and to understand the important factors for technique approval.

METHODS: Semi-structured interviews were conducted with parents with recent experience of a premature birth. Recruitment was through the Northern Ireland premature infant charity, Tinylife. Interviews progressed until data saturation was reached and thematic analysis employed.

KEY FINDINGS: The study included 16 parents. Parental support for MN-mediated monitoring was evident, alongside the unpopularity of traditional blood sampling in neonates. Factors facilitating MN approval included the opportunity for pain reduction, the simplicity of the procedure, the potential for increased parental involvement and the more favourable appearance, owing to the minute size of MNs and similarities with a sticking plaster. Confirmation of correct application, a pain-free patch removal and endorsement from trusted healthcare professionals were important.

CONCLUSION: These findings will inform researchers in the field of MN development and enlighten practitioners regarding parental distress resulting from conventional blood sampling. Further work is necessary to understand MN acceptability among practitioners. This work should assist in the development of an acceptable MN device and facilitate the reduction of parental distress.

Interventions infirmières relatives à l'allaitement maternel de nouveau-nés prématurés

Problématique. Basée sur les constats effectués lors d’un essai clinique randomisé qui visait à évaluer les effets du lait maternel de fin d’expression sur la croissance et le développement de nouveau-nés prématurés et qui s’est soldé par un recrutement infructueux, une intervention de soutien à la lactation chez les mères de nouveau-nés prématurés a été développée. La mère d’un nouveau-né prématuré est en effet trois fois plus à risque qu’une autre de présenter une production lactée insuffisante. Il est donc crucial de soutenir ces mères dans l’établissement et le maintien d’une production lactée adéquate. Le but de cette étude pilote est d’estimer les effets d’une intervention de soutien à la lactation sur l’expression de lait maternel et la production lactée de mères ayant donné naissance prématurément ainsi que d’évaluer les aspects d’acceptabilité et de faisabilité de l’intervention, de l’étude et de ses procédures. Hypothèse de recherche. Les mères de nouveau-nés prématurés qui reçoivent une intervention de soutien à la lactation expriment leur lait significativement plus longtemps et plus fréquemment et produisent significativement un plus grand volume de lait à plus grande concentration lipidique sur une base quotidienne que celles qui reçoivent les soins usuels. Méthode. Devis : Projet-pilote de type essai clinique randomisé. Échantillon: Quarante mères de nouveau-nés prématurés de <30 semaines de gestation admis à une unité de soins intensifs néonatals. Procédures: Les mères du groupe témoin reçoivent les soins usuels alors que celles du groupe expérimental reçoivent une intervention de soutien à la lactation. Cette dernière comporte quatre volets: une séance d’enseignement portant sur l’établissement et le maintien d’une production lactée suffisante, un suivi téléphonique, une ligne d’aide téléphonique et le prêt d’un tire-lait électrique double pompage. Dans les deux groupes, les mères sont amenées à tenir un journal de bord de leurs séances d’expression et du volume de lait maternel exprimé. Résultats. L’étude et ses procédures de même que l’intervention de soutien sont acceptables et faisables. Les résultats observés en lien avec l’hypothèse de recherche sont orientés dans la même direction que cette dernière à l’exception de la concentration lipidique du lait maternel. Recommandations. Une étude à plus grande échelle doit être réalisée afin d’évaluer les effets de l’intervention de soutien à la lactation sur la production lactée de mères de nouveau-nés prématurés. Quant à la clinique, des actions concertées doivent être menées afin de créer un contexte propice et des conditions favorables à l’expression de lait maternel chez les mères de nouveau-nés prématurés.

Prevalencia y factores asociados al embarazo y su reincidencia en adolescentes colombianas

Introducción: El embarazo en adolescentes es uno de los problemas de salud pública más relevantes a nivel mundial. En Colombia, las políticas no han sido efectivas para disminuir la tasa de embarazo en edades tempranas, ni para impedir la reincidencia de la gestación. Este estudio caracteriza esta problemática determinando la prevalencia y los factores asociados tanto del embarazo en adolescentes como de su reincidencia. Métodos: Estudio de corte transversal comparativo a partir de 13,313 adolescentes colombianas respondientes de la Encuesta Nacional de Demografía y Salud, 2010. Se realizaron regresiones multinomiales para comparar el grupo de adolescentes no embarazadas con las que tuvieron uno o varios embarazos y regresión logística para comparar el grupo de embarazo único y el reincidente. Resultados: El 13.3% tuvieron un embarazo y el 3.5% más de uno. Al comparar con las adolescentes que no se embarazaron: a) las adolescentes que tuvieron un embarazo fueron mayores, convivían con su pareja, vivían con más personas, fuera de la familia de origen y habían sido víctimas de abuso sexual y maltrato físico. La probabilidad de embarazo disminuyo en aquellas adolescentes que tenían más recursos económicos, deseaban un menor número de hijos, asistían al colegio, habían usado planificación familiar y recibido educación sexual. b) En las adolescentes que tuvieron más de un embarazo se asociaron los mismos factores sin embargo no hubo diferencias regionales ni asociación con el número deseado de hijos, se encontraron otros factores como el menor nivel educativo y las mujeres de raza negra. La reincidencia también se asocio con la edad mayor del primer compañero sexual, la ausencia de control prenatal y haber tenido un recién nacido prematuro. Conclusiones: Este estudio utilizó una muestra representativa de las adolescentes colombianas. Demuestra tanto las dimensiones del problema como los factores que se encuentran asociados al mismo con lo cual se podrán direccionar programas de prevención adecuados

Cafeina vs aminofilina para la apnea del prematuro: estudio randomizado

La apnea del prematuro es una patología frecuente que se presenta en el 85% de los recién nacidos menores de 34 semanas de edad gestacional y en el 95-100% de los menores de 28 semanas. Con respecto al peso al nacer, se manifiesta en el 92% de los de peso menor a 1250 gramos y en el 50% de los de peso menor a 1500 gramos. Desde 2003, se aprobó en Colombia el uso de citrato de cafeína para la prevención y el tratamiento de la apnea del prematuro, basados en la evidencia. Metodología: Se realizó un estudio de interención simple comparando el citrato de cafeína con la aminofilina para la prevención y manejo de la apnea en pretérminos menores de 35 semanas de edad. Resultados: Se incluyeron 118 recién nacidos pretérminos de los cuales 18,6% fueron menores de 28 semanas, 79,7% de 34 semanas y dos 1,7% mayores o iguales a 34,1 semanas. 56 neonatos recibieron citrato de cafeína. De éstos, 33,9% de forma profiláctica y 66,1%, terapéutica; 28 (23,7%) recibieron aminofilina y 34 (28,8%) no recibieron ninguno de los dos medicamentos. El citrato de cafeína mostró menos efectos secundarios comparado con aminofilina (p <0,01). Discusión: El citrato de cafeína, administrado en forma profiláctica o terapéutica, mostró resultados superiores, estadísticamente significativos, en comparación con aminofilina y con los controles sin tratamiento, para la prevención y el tratamiento de la apnea del prematuro, presentando, además, menores efectos secundarios.

Terapias no farmacológicas en el manejo del dolor en neonatos pretérmino. revisión sistemática de la literatura

Antecedentes El dolor en neonatos ha sido un problema poco explorado. Se ha propuesto el uso de las terapias no farmacológicas para su tratamiento, sin embargo existen pocas aproximaciones sistemáticas para la evaluación de su eficacia. Objetivos Determinar la eficacia de las terapias no farmacológicas en el manejo del dolor en neonatos pretérmino a través de una revisión sistemática. Metodología Se realizó una revisión sistemática de la literatura para evaluar la eficacia de las terapias no farmacológicas en el manejo del dolor en el recién nacido petérmino. La búsqueda se realizó a través de las bases de datos Embase, Cochrane, Bireme y Embase. Se identificaron estudios publicados inglés y español. Se realizó un análisis cualitativo y cuantitativo. Resultados Se incluyeron 10 ensayos clínicos. La solución de sacarosa administrada por vía oral mostró reducir la intensidad del dolor en el recién nacido. La intubación y toma de muestras facilitada por el cuidador mostró también reducir la intensidad del dolor. Conclusión Se recomienda la administración solución de sacarosa y acompañamiento del cuidador durante los procedimientos como medidas para reducir el dolor en el recién nacido pretérmino.

Morbilidad y mortalidad en prematuros menores de 1500 gramos en un hospital regional del 2011 a 2013

Introducción: El presente estudio pretende determinar la mortalidad y caracterizar morbilidad de este grupo de recién nacidos, para establecer planes de mejoramiento. Materiales y método: Estudio descriptivo retrospectivo de corte transversal. Se revisaron 158 historias clínicas de los recién nacidos prematuros menores de 1500 gramos hospitalizados en la unidad de cuidados intensivos neonatales del Hospital Universitario Departamental de Nariño durante el periodo 2011 al 2013. La información fue analizada estadísticamente. Resultados: Se encontró que de 5447 nacidos vivos el 2,9 % fueron menores de 1500 gramos. 52,5 % eran de género masculino, 63,9% nacieron por cesárea. El 23,4 % no recibió esteroides antenatales. La tasa de mortalidad para el periodo de estudio en este grupo de pacientes fue de 7.3 por mil nacidos vivos. El 100% de los recién nacidos de menos de 750 gr fallecieron. Mientras que no se registro ninguna sobrevida de menos de 24 semanas. Conclusiones: Podría establecerse este como límite de viabilidad el peso al nacer < 750 gr y menos de 24 semanas de gestación, en donde la muerte es prácticamente la regla, siempre teniendo en cuenta evaluar cuidadosamente cada caso particular. La morbilidad de los prematuros de muy bajo peso al nacer esta en los rangos reportados en la literatura.

Metoder för att främja amning av prematura barn : en systematisk litteraturstudie

Syftet med denna studie var att beskriva vilka metoder som användes på en neonatalavdelning för att främja amningen hos prematura barn. Arbetet är en systematisk litteraturstudie där 15 vetenskapliga artiklar användes. Litteratursökningen gjordes i databaserna Blackwell Synergy, CINAHL, Elin@dalarna, PubMed och Medline. Litteraturgenomgången visade att det fanns ett flertal metoder för att främja amning av prematura barn på neonatalavdelningen. Föräldrarna behöver få hjälp av personalen att skapa sociala band till sitt barn och med att förstå att det är dem som är av största betydelse för barnet. NIDCAP-vård var en omvårdnadsmodell som underlättade för samspelet mellan mor och barn. Mamman behöver ständig uppmuntran av personalen och pappan för att lyckas med sin amning. Studier har visat att känguruvård har positiva effekter på amningen och för att utveckla ett tidigt sugbeteende. Barnets tidiga kontakt vid mammas bröst och att mamman så snart som möjligt efter förlossningen börjar pumpa ur bröstmjölk främjar amningen. Andra metoder som främjar amning är att barnet fått känna doften av mammans mjölk och att mamman fått tillgång till en personlig ”amningsexpert”. Tillmatning med kopp eller användning av amningsnapp var metoder som visade sig öka chansen till amning samt bröstmjölkskonsumtionen hos prematura barn.

Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk

Two cases of zinc deficiency in breastfed neonates were investigated where zinc levels in the mothers' milk were reduced by more than 75 % compared to normal. The objective of this study was to find the molecular basis of the maternal zinc deficiency condition. Significant reductions in mRNA expression and protein levels of the zinc transporters SLC30A5 and SLC30A6 were found in maternal tissue, suggesting a causal link to the zinc-deficient milk. Novel splice variants of the SLC30A6 transcript were detected. No modifications were found in coding regions, or in transcription binding sites of promoter regions or in 5' and 3' untranslated regions of both transporters in lymphoblasts and fibroblasts isolated from both mothers. Altered DNA methylation in SLC30A5 at two CpG sites was detected and may account for the reduced levels of SLC30A5 mRNA and protein in lymphoblasts. Reduced SLC30A6 mRNA and protein levels in lymphoblasts may be secondary to reduced SLC30A5 expression, as they function as a heterodimer in zinc transport. In conclusion, two cases of zinc deficiency are linked to low levels of the SLC30A5 and SLC30A6 zinc transporters. These two zinc transporters have not been previously associated with zinc deficiency in milk.

O exame neurológico do recém-nascido pré-termo não complicado: avaliação pela escala de saint-anne dargassies, e screening pelas escalas de amiel-barrier-shnider modificada e prechtl ao termo

This study compared the evolution of posture, tone and neonatal reflexes in preterm infants without clinical or neurological complications before and after the age of term using the scale of Saint-Anne Dargassies. To reach the age of the term, was applied Scales Amiel-Barrier-Shnider changed and the Prechtl, traditionally used in the evaluation of term newborns, looking for possible changes to the term, while also evaluating the sensitivity of these scales. We studied 20 non-complicated preterm infants, both sexes aged 32-36 weeks, born in Januário Cicco Maternity School, from August 2006 to August 2007. Was applied to the scale of Saint-Anne Dargassies every two weeks until reach the term, and the range of Amiel-Barrier-Shnider changed and the Prechtl, after reaching 39 and 41 weeks. The evaluation result of articular angles was subjected to the test of Friedman ANOVA, significant differences between the three measurements of the scale of Saint-Anne Dargassies only for angles heel-to-ear to term. Neonatal reflexes changed in the period of prematurity were the cardinal points reflexes, Moro reflexes, cross extensions reflex and the automatic walking reflexes. The posture was the parameter which remained unchanged in the three scales. Considering a significance level of 5% by applying Cochran Q Test, it was found that the scale of Saint-Anne Dargassies is more sensitive to detect suspects. With this methodology and the results it was possible to prepare a manuscript: The neurological examination of non-complicated preterm newborns using the Sanit-Anne Dargssies Scale from birth to term: normal or altered? In which we describe that despite the good clinical condition, the RNP show changes in tone and neonatal reflexes. These data are important because though non-complicated RNP need further attention its maturation process, enabling us to detect and intervene early. With these results we can build a scale simplified neurological assessment made with items found most altered during the application of three scales. The development of this project has a multidisciplinary approach, because it involved Paediatric Neurologist, Physiotherapist and Neonatologist, as recommended by PPGCSA