Respiratory symptoms in preterm infants: burden of disease in the first year of life

Objective While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. Methods Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. Main outcome measures: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). Patients: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. Results Cough occurred in 80%, wheeze in 44%, rehospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR and CRIB-Score. Conclusions Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

[Iatrogenic preterm births and late preterm births of 340/7 to 366/7 - risks and chances]

Late preterm births with a gestational age of 340/7-366/7 are physiologically, anatomically and metabolically immature and develop medical complications significantly more frequently, have a high morbidity and an elevated mortality. Consideration of this knowledge will in future require new strategies for obstretric, peripartal and neonatal management options that take into account not only maternal risks and demands but also those of the infant.

Surfactant replacement therapy in preterm infants: a European survey

Exogenous surfactant is an undisputed treatment for neonatal respiratory distress syndrome but its efficacy is highly dependent on the treatment strategy. International guidelines have published recommendations on the optimal surfactant replacement strategy.

Interobserver variability in assessment of cranial ultrasound in very preterm infants

Cranial ultrasound (cUS) findings help doctors in the clinical management of preterm infants and in their discussion with parents regarding prediction of outcome. cUS is often used as outcome measure in clinical research studies. Accurate cUS performance and interpretation is therefore required.

Maturation of endogenous glucose production in preterm and term calves

Glucose disposability is often impaired in neonatal calves and even more in preterm calves. The objective of this study was to investigate ontogenic maturation of endogenous glucose production (eGP) in calves and its effects on postnatal glucose homeostasis. Calves (n = 7 per group) were born preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery), or spontaneously born and fed colostrum for 4 d (TC). Blood samples were taken immediately after birth and before and 2h after feeding at 24h after birth (PT; T) or on d 4 of life (TC) to determine metabolic and endocrine changes. After birth (PT and T) or on d 3 of life (TC), fasted calves were gavaged with deuterium-labeled water to determine gluconeogenesis (GNG) and intravenously infused with [U(13)C]-glucose to measure eGP and glucose oxidation (GOx) in blood plasma. After slaughter at 26h after birth (PT, T) or on d 4 of life (TC), glycogen concentrations in liver and hepatic mRNA concentrations and enzyme activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase were measured. Preterm calves had the lowest plasma concentrations of cortisol and 3,5,3'-triiodothyronine at birth. Plasma glucose concentrations from d 1 to 2 decreased more, but plasma concentrations of lactate and urea and glucagon:insulin ratio were higher in PT than in T and TC calves. The eGP, GNG, GOx, as well as hepatic glycogen concentrations and PEPCK activities, were lowest in PT calves. Results indicate impaired glucose homeostasis due to decreased eGP in PT calves and maturation of eGP with ontogenic development.

Stem Cells From Umbilical Cord Wharton's Jelly From Preterm Birth Have Neuroglial Differentiation Potential

Objective:The aim of the study is to determine the neuroglial differentiation potential of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from preterm birth when compared to term delivery.Study Design:The WJ-MSCs from umbilical cords of preterm birth and term controls were isolated and induced into neural progenitors. The cells were analyzed for neuroglial markers by flow cytometry, real-time polymerase chain reaction, and immunocytochemistry. Results:Independent of gestational age, a subset of WJ-MSC displayed the neural progenitor cell markers Nestin and Musashi-1 and the mature neural markers microtubule-associated protein 2, glial fibrillary acidic protein, and myelin basic protein. Neuroglial induction of WJ-MSCs from term and preterm birth resulted in the enhanced transcription of Nestin and Musashi-1.Conclusions:Undifferentiated WJ-MSCs from preterm birth express neuroglial markers and can be successfully induced into neural progenitors similar to term controls. Their potential use as cellular graft in neuroregenerative therapy for peripartum brain injury in preterm birth has to be tested.

Physiological parameters after nonpharmacological analgesia in preterm infants: a randomized trial

To compare the influence of three different nonpharmacological interventions on cortical activation, heart rate and peripheral oxygen saturation (SaO2 ) after heelstick in preterm infants.

Cognitive and behavioral aspects of executive functions in children born very preterm

This study investigated whether children aged between 8 and 12 years born very preterm (VPT) and/or at very low birth weight (VLBW) performed lower than same-aged term-born controls in cognitive and behavioral aspects of three executive functions: inhibition, working memory, and shifting. Special attention was given to sex differences. Fifty-two VPT/VLBW children (26 girls, 50%) born in the cohort of 1998-2003 and 36 same-aged term-born children (18 girls, 50%) were recruited. As cognitive measures, children completed tasks of inhibition (Color-Word Interference Test, D-KEFS; Delis, Kaplan, & Kramer, 2001 ), working memory (digit span backwards, HAWIK-IV; Petermann & Petermann, 2008 ), and shifting (Trail Making Test, number-letter-switching, D-KEFS; Delis et al., 2001 ). As behavioral measures, mothers completed the Behavior Rating Inventory of Executive Function (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000 ). Scales of interest were inhibit, working memory, and shift. Analyses of the cognitive aspects of executive functions revealed that VPT/VLBW children performed significantly lower than controls in the shifting task but not in the working memory and inhibition tasks. Analyses of behavioral aspects of executive functions revealed that VPT/VLBW children displayed more problems than the controls in working memory in everyday life but not in inhibition and shifting. No sex differences could be detected either in cognitive or behavioral aspects of executive functions. To conclude, cognitive and behavioral measures of executive functions were not congruent in VPT/VLBW children. In clinical practice, the combination of cognitive and behavioral instruments is required to disclose children's executive difficulties.

Executive functions of children born very preterm--deficit or delay?

This cross-sectional study examined the performance of children born very preterm and/or at very low birth weight (VPT/VLBW) and same-aged term-born controls in three core executive functions: inhibition, working memory, and shifting. Children were divided into two age groups according to the median (young, 8.00-9.86 years; old, 9.87-12.99 years). The aims of the study were to investigate whether (a) VPT/VLBW children of both age groups performed poorer than controls (deficit hypothesis) or caught up with increasing age (delay hypothesis) and (b) whether VPT/VLBW children displayed a similar pattern of performance increase in executive functions with advancing age compared with the controls. Fifty-six VPT/VLBW children born in the cohort of 1998-2003 and 41 healthy-term-born controls were recruited. All children completed tests of inhibition (Color-Word Interference Task, Delis-Kaplan Executive Function System (D-KEFS)), working memory (Digit Span Backwards, HAWIK-IV), and shifting (Trail Making Test, Number-Letter Sequencing, D-KEFS). Results revealed that young VPT/VLBW children performed significantly poorer than the young controls in inhibition, working memory, and shifting, whereas old VPT/VLBW children performed similar to the old controls across all three executive functions. Furthermore, the frequencies of impairment in inhibition, working memory and shifting were higher in the young VPT/VLBW group compared with the young control group, whereas frequencies of impairment were equal in the old groups. In both VPT/VLBW children and controls, the highest increase in executive performance across the ages of 8 to 12 years was observed in shifting, followed by working memory, and inhibition.

Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008

Background While survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling. Methods Prospective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7 and 276/7 weeks gestational age during 2000–2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System. Results Of 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p < 0.001). At 360/7 weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p < 0.05). Survival without moderate or severe ND increased from 27% to 39% during the observation period (p = 0.02). Conclusions In this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability.

The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates. A systematic literature review

BACKGROUND: Neonates in a neonatal intensive care unit are exposed to a high number of painful procedures. Since repeated and sustained pain can have consequences for the neurological and behaviour-oriented development of the newborn, the greatest attention needs to be paid to systematic pain management in neonatology. Non-pharmacological treatment methods are being increasingly discussed with regard to pain prevention and relief either alone or in combination with pharmacological treatment. AIMS: To identify effective non-pharmacological interventions with regard to procedural pain in neonates. METHODS: A literature search was conducted via the MedLine, CINAHL, Cochrane Library databases and complemented by a handsearch. The literature search covered the period from 1984 to 2004. Data were extracted according to pre-defined criteria by two independent reviewers and methodological quality was assessed. RESULTS: 13 randomised controlled studies and two meta-analyses were taken into consideration with regard to the question of current nursing practice of non-pharmacological pain management methods. The selected interventions were "non-nutritive sucking", "music", "swaddling", "positioning", "olfactory and multisensorial stimulation", "kangaroo care" and "maternal touch". There is evidence that the methods of "non-nutritive sucking", "swaddling" and "facilitated tucking" do have a pain-alleviating effect on neonates. CONCLUSIONS: Some of the non-pharmacological interventions have an evident favourable effect on pulse rate, respiration and oxygen saturation, on the reduction of motor activity, and on the excitation states after invasive measures. However, unambiguous evidence of this still remains to be presented. Further research should emphasise the use of validated pain assessment instruments for the evaluation of the pain-alleviating effect of non-pharmacological interventions.

Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants

BACKGROUND: A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries. OBJECTIVE: To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants. DESIGN: Sixteen preterm neonates of <34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography. RESULTS: The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO2, and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively). CONCLUSION: A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.

The Young's modulus of fetal preterm and term amniotic membranes

OBJECTIVE: To examine the Young's modulus of the human amniotic membranes, as well as its relationship to gestational age. To determine whether cellular and material-related parameters affect this modulus. STUDY DESIGN: In a prospective study at the Obstetric outpatient clinic of the University Hospital Zurich Young's modulus, thickness and mesenchymal:epithelial cell ratio of amniotic membranes of preterm (N=23) and term (N=40) placentae were examined. Significance (P<0.05) was calculated with the Mann-Whitney two-sample rank sum test and Wilcoxon signed rank test, while correlations were made using the Spearman's correlation. RESULTS: The Young's modulus of preterm amniotic membranes was significantly higher than that of term membranes. It varied within the same amniotic membrane. The thickness of the amnion in both preterm and term membranes did not differ significantly. The thinner the preterm and term amniotic membranes, the higher the Young's modulus was. There was no relation to the mesenchymal:epithelial cell ratio in the amnion. CONCLUSIONS: Preterm amniotic membranes are stiffer than term amniotic membranes. Tentatively, we hypothesise that there may be a correlation between the extracellular matrix components and the elastic properties of the membrane.