Impact of Retinopathy of Prematurity on Visual Motor Integration.

BACKGROUND: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age. METHODS: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years. RESULTS: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01). CONCLUSION: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.

In vitro comparison of noise levels produced by different CPAP generators.

INTRODUCTION: Minimization of noise exposure is an important aim of modern neonatal intensive care medicine. Binasal continuous positive airway pressure (CPAP) generators are among the most important sources of continuous noise in neonatal wards. The aim of this study was to find out which CPAP generator creates the least noise. METHOD: In an experimental setup, two jet CPAP generators (Infant Flow® generator and MediJet®) and two conventional CPAP generators (Bubble CPAP® and Baby Flow®) were compared. Noise production was measured in decibels in an A-weighted scale [dB(A)] in a closed incubator at 2 mm lateral distance from the end of the nasal prongs. Reproduction of constant airway pressure and air leak was achieved by closure of the nasal prongs with a type of adhesive tape that is semipermeable to air. RESULTS: The noise levels produced by the four generators were significantly different (p < 0.001). Values measured at a continuous constant flow rate of 8 l/min averaged 83 dB(A) for the Infant Flow® generator with or without sound absorber, 72 dB(A) for the MediJet®, 62 dB(A) for the Bubble CPAP® and 55 dB(A) for the Baby Flow®. CONCLUSION: Conventional CPAP generators work more quietly than the currently available jet CPAP generators.

Variety of expiratory resistance between different continuous positive airway pressure devices for preterm infants.

Continuous positive airway pressure (CPAP) systems for preterm infants work with conventional ventilators or use a jet ventilation system. It is assumed that the most important advantage of jet-CPAP systems is a lower expiratory resistance (R(E) ). We investigated the R(E) of seven different CPAP systems. We studied two primary-care CPAP systems, three jet-CPAP generators, and two conventional CPAP devices. All devices were adjusted at 6 mbar and connected with a test lung simulating a standardized expiration volume. Maximum pressure increase during expiration was measured and maximum R(E) was calculated. In primary-care CPAP devices, the maximum R(E) of the Benveniste valve was 9.7 mbar/L/s (SD 1.2) while that of the Neopuff was 102.8 mbar/L/s (SD 7.9) (P < 0.01). In jet-CPAP devices, the R(E) of the Infant Flow was 6.8 mbar/L/s (SD 1.7), the one of the Medijet REF 1000 was 43.5 mbar/L/s (SD 1.5), and that of the Medijet REF 1010 was 36.7 mbar/L/s (SD 0.3) (P < 0.01). In conventional CPAP systems, the R(E) of the Baby Flow was 29.7 mbar/L/s (SD 1.1) and that of the Bubble CPAP was 37.1 mbar/L/s (SD 4.3) (P < 0.01). All CPAP devices created an R(E). Jet-CPAP devices did not produce lower R(E) than conventional CPAP devices.

Danger of low pressure alarm failure in preterm infants on continuous positive airway pressure.

In certain settings of conventional continuous positive airway pressure (CPAP) application, the ventilator may not be able to detect dislodgement of the prongs. This occurs especially in settings with high flow and small prongs. We investigated the relation between ventilator flows, size of the nasal prongs, and pressure generated within the ventilator circuit due to the flow resistance of the prongs. We studied a Baby-flow CPAP connected to a Babylog 8000plus ventilator. Five prongs of increasing size (x-small, small, medium, large, x-large) and one nose mask were connected to the CPAP in turn. Starting at 30 lpm, the flow was reduced in 2 lpm steps. The dynamic pressure caused by the flow resistance of the prongs within the ventilator circuit was recorded. For all devices, we observed a correlation between the reduction of the flow and the reduction in pressure within the ventilator circuit. However, the flow resistance of the x-small prongs generated the highest dynamic pressure (30 mbar at 22 lpm) within the ventilator circuit while the mask gave rise to the lowest pressure (9 mbar at 30 lpm). The pressure value generated with x-small prongs at low flow rate was observed at high flow rate with x-large prongs or with a mask. We conclude that in settings with high flow rates, low CPAP levels, and small prongs, the resistance of the prongs will create enough dynamic pressure within the ventilator circuit to permit the ventilator to compensate a large leakage flow by closing the expiratory valve. Thus, in case of dislodgement of the prongs, the pressure within the ventilator circuit will not decrease below the alarm level, and the machine will not be able to generate an alarm.

Long hospitalization is the most important risk factor for early weaning from breast milk in premature babies.

AIM: To identify certain variables related to the infants' course that might have an impact on the mothers' decision to breastfeed. PATIENTS AND METHOD: Retrospective survey including all patients <1500 g birth weight (BW) treated between January 1, 2000 and December 31, 2005 at the Neonatal Intensive Care Unit of the Medical University of Vienna who were not transferred to another hospital. Multiple regression analysis of the following variables was carried out: gestational age (GA), BW, length of stay (LOS), parity, singleton or multiple gestation, sex and severe morbidity. RESULTS: Of the 239 patients included, 142 (60%) were fed breast milk at the time of final discharge, 97 (40%) were fed formula. LOS was significantly correlated with the probability of being breastfed: the shorter it was, the higher was the probability of being breastfed at the time of final discharge (p = 0.0064 for singletons, p = 0.001 for multiples). Lower GA also increased the probability of being breastfed, but this was only statistically significant for multiples (p = 0.001). CONCLUSION: This study shows clearly that the most important influencing factor on the mothers' decision to continue breastfeeding is the LOS. Thus more emphasis should be put on encouraging mothers to continue lactation throughout their babies' hospital stay.

Must screening examinations for retinopathy of prematurity necessarily be painful?

PURPOSE: This study investigates the impact of the length of the examination, the insertion of eyelid specula, and the indentation of the globe on the pain and stress sensation of premature infants. METHODS: Ninety-two premature infants in three neonatal wards were included. In two wards, the patients were examined using eyelid specula and scleral indentation as recommended in the official guidelines. In the third ward, the investigation time was minimized and ophthalmoscopy was performed without eyelid specula and scleral indentation. Physical and mental disturbance of the patients was assessed by the Neonatal Infant Pain Score and by monitoring the heart rate. The results were divided into two groups: in the one, eyelid specula and scleral indentation were used, whereas in the other one, they were not used. An independent-samples t-test was performed, which allowed us to calculate the correlation between the way the examination was executed and the condition of the patients. RESULTS: Demographic data and baseline values of heart rate and pain score did not differ between the two groups. Heart rate and pain score during and after the investigation were significantly higher and increased significantly with the duration of the examination for the patients who were investigated using lid specula and scleral indentation. CONCLUSION: Our study shows that indirect ophthalmoscopy without specula causes significantly less stress to infants than screening with lid specula and scleral indentation.

Hippocampal metabolic proteins are modulated in voluntary and treadmill exercise rats.

Systematic protein expression studies in the brain of exercising and sedentary animals have not been carried out so far and it was therefore decided to determine differences in metabolic protein levels in rat hippocampus of sedentary, voluntary and involuntary exercising rats by a proteomic approach. Aged, male Sprague-Dawley rats, 23 months old, were used for the study: the first group consisted of sedentary rats, the second of rats with voluntary exercise from five to 23 months and the third group was performing involuntary exercise on a treadmill from five to 23 months. Two-dimensional gel electrophoresis with subsequent mass spectrometrical identification of spots followed by quantification of spots was carried out. Identification of significantly differential proteins was validated by the determination of the corresponding enzyme activity. Five individual metabolic proteins showed differential protein levels in the three groups: mitochondrial precursors of ornithine aminotransferase, isocitrate dehydrogenase [NAD] subunit alpha, malate dehydrogenase, ubiquinol-cytochrome-c reductase complex core protein 1, and ubiquitin carboxyl-terminal hydrolase isozyme L1. The unambiguously identified metabolic proteins were mainly of mitochondrial localization and fit the expectations of altered mitochondrial activity in exercise. Reduced ubiquitin carboxyl-terminal hydrolase isoenzyme L1 levels in treadmill (forced) exercise show the involvement of the proteasomal pathway as a novel finding. These results not only form the basis for functional studies elucidating mechanisms and differences between voluntary and forced exercise in hippocampal metabolism but also highlight the most intriguing aspect that exercise is affecting the brain at the protein level.

A new modified Seldinger technique for 2- and 3-French peripherally inserted central venous catheters.

This study describes a modified Seldinger technique for 2- and 3-French peripherally inserted central venous catheters: A device similar to that used in heart catherisation with a standard micro-introducer serving as sheath and an arterial catheter serving as inner dilator was pushed forward over a wire guide that had before been inserted via a peripheral venous catheter. With this method 2-and 3-French catheters could be safely inserted into peripheral veins of 14 paediatric patients. In conclusion successful insertion of a small peripheral venous catheter offers in most cases a possibility for the placement of a central venous line.

Amnionitis with Ureaplasma urealyticum or other microbes leads to increased morbidity and prolonged hospitalization in very low birth weight infants.

OBJECTIVE: To investigate the influence of culture proven intrauterine infection on preterm morbidity and to test the effect of antimicrobial treatment. METHODS: Retrospective cohort study conducted between October 1997 and February 2001 in patients with preterm premature rupture of membranes or preterm labor. Vaginal swabs were sampled and amniocentesis for microbiologic culture of the amniotic fluid was performed. Patients with Ureaplasma urealyticum in the amniotic fluid were treated with josamycin. Infants were followed post partum according to birth weight, gestational age, APGAR score and infant morbidity. RESULTS: In 49 eligible patients, 40% of cultures were positive, 22% for Ureaplasma urealyticum, 12% for other bacteria and 6% for candida. Children of mothers with positive amniotic fluid cultures had significantly lower gestational ages (26+4 weeks for Ureaplasma urealyticum [p=0.04] and 25+5 weeks for other microorganisms [p=0.0017] versus 28+6 weeks for mothers with negative amniotic fluid cultures) and lower birth weights (975 g [n.s.] and 828 g [p=0.0072] versus 1,041 g) but were appropriate for their gestational ages. 33.3% and 66.7% versus 24% of the children were mechanically ventilated [n.s.], duration of mechanical ventilation was 5.3 [p=0.02] and 10.1 days [p=0.04] versus 1.4 days, and prevalence of chronic lung disease was 38% and 33% versus 11% [n.s.]. Prevalence of severe intraventricular hemorrhage (12.5% [n.s.] and 33% [p=0.04] versus 3.4%) and nosocomial infections (50% for both groups of positive cultures versus 10.3% for negative cultures, p=0.02 and 0.03, respectively) was higher and median length of stay was significantly longer (121 [p=0.02] and 107 days [p=0.03] versus 60 days) in these patients. Maternal positive vaginal swab cultures were not associated with any of the above-mentioned factors. In none of the patients treated with macrolids for proven Ureaplasma urealyticum amnionitis could the microbes be eradicated. CONCLUSION: Maternal positive amniotic fluid cultures have been associated with lower gestational age and lower birth weight. Rate of infant morbidity was higher and length of stay was significantly longer in this group. Positive vaginal swabs were not predictive for infant morbidity. Treatment of mothers showing positive amniotic fluid cultures with macrolids was not effective.

A flow sensor suitable for use with split-flow ventilation--first preclinical data.

Volutrauma caused by artificial ventilation represents a major morbidity risk for premature infants. Our working group has recently developed an innovative "split-flow ventilation" system aiming at the reduction of tidal volumes (TVs). The main problem for the practical use of this system is the fact that conventional measurements of commercially available flow sensors are distorted by the split flow. In this study, we present the first preclinical data from testing an adapted flow sensor combination recognizing the split flow. A preterm infant test lung was conventionally ventilated, modified by insertion of a split-flow line. In addition to the customary flow sensor (FS-1), a second flow sensor (FS-2) was integrated into the split-flow line, and a third (FS-3) was placed at the exit of the test lung for reference measurements. The signals of all three flow sensors were read and processed by a computer. The program was set to graphically add up flow curves 1, 2, and 3 during one ventilation loop. After 10 runs, a mean curve of FS-1+2 was calculated and compared to the mean curve of FS-3. Furthermore, the mean TV of 10 runs measured by FS-1+2 was calculated and compared with the mean TV calculated by FS-3. The summation curve FS-1+2 proved identical to the reference curve FS-3. FS-1+2 yielded a TV of 6.6 +/- 0.01 mL (inspiratory) and 6.7 +/- 0.02 mL (expiratory). The corresponding values of FS-3 were 6.5 +/- 0.20 mL and 6.6 +/- 0.09 mL, respectively. According to our results, the presented flow sensor constellation allows exact flow measurements in the experimental setting and appears suitable for usage in a split-flow ventilation circuit under clinical conditions.

Trends in infant mortality in Austria between 1984 and 2002.

Infant mortality rate is an important medical indicator and is often used for comparing countries with respect to welfare and public health. Among other factors, effective medical technology, better access to pre- and postnatal care for all socioeconomic groups and better nutrition have decreased infant mortality in Austria from about 200 deaths per 1000 live births at the beginning of the 20th century to about 5 deaths per 1000 live births at the end. In this study we present the trends in infant mortality, based on 1,654,519 individual birth records, in Austria since 1984. The infant mortality rate dropped rapidly from about 12 per 1000 live births in 1985 to 4.6 per 1000 live births during the last two years of our study (2001/02). Infant mortality rates stratified by cause of death show somewhat differing trends. In particular, the number of deaths due to peripartal problems decreased as the result of improvements in obstetrics and neonatology, but in 1995 a change in the definition of live birth led to a rise of about 20% in the stillbirth rate. At present, Austria has one of the lowest infant mortality rates of all European countries; however, between 1999 and 2002 the mortality rate has been fairly static. A further reduction in mortality clearly cannot be achieved by advances in medicine alone. It remains a challenge for health politicians, physicians and society at large to reduce the prevalence of well-known risk factors such as alcohol abuse, heavy overweight and smoking during pregnancy.

Effect of the Y-piece of the ventilation circuit on ventilation requirements in extremely low birth weight infants.

OBJECTIVE: Volutrauma caused by high tidal volumes contributes considerably to the development of bronchopulmonary dysplasia. Yet high tidal volumes are required to overcome dead space. In an experimental arrangement we tested whether reduction of dead space might reduce ventilation requirements and thus reduce volutrauma in preterm infants. MATERIALS AND METHODS: The time required to eliminate CO2 by standardized mechanical ventilation from a preterm infant's test lung flooded with CO2 was measured. Four different Y-pieces and flow sensor combinations were tested with and without a device for closed suction: Y-piece without flow sensor; integrated flow sensor; small dead-space flow sensor; and a new dead-space free-flow sensor for preterm infants. CO2 concentrations were measured by a capnograph. Mean CO2 elimination times (+/-SD) were compared. RESULTS: Mean CO2 elimination time was 37.5 s (+/-1.18 s) with and 37.4 s (+/-0.97 s) without closed suction device for the Y-piece without flow sensor, 47.7 s (+/-0.82 s) and 45.5 s (+/-1.18 s) for the integrated flow sensor, 42.5 s (+/-1.27 s) and 41.1 s (+/-0.99 s) for the small dead-space flow sensor and 38.3 s (+/-1.16 s) and 36.8 s (+/-0.79 s) for the dead-space free-flow sensor. CONCLUSION: CO2 elimination time with and without closed suction device was nearly identical for the Y-piece without flow sensor and for the dead-space free-flow sensor. With both systems, ventilation requirements were significantly lower than for the integrated flow sensor and for the small dead-space flow sensor (integrated flow sensor vs dead-space free-flow sensor 23.6 and 24.5%, respectively, small dead-space flow sensor vs dead-space free flow sensor 11.7 and 10.9%, respectively); thus, we think that introduction of the innovative dead-space free-flow sensor into clinical practice might reduce incidence and severity of bronchopulmonary dysplasia by reduction of volutrauma.

Is the use of early nasal CPAP associated with lower rates of chronic lung disease and retinopathy of prematurity? Nine years of experience with the Vermont Oxford Neonatal Network.

OBJECTIVE: The neonatal regional tertiary care center of the University of Vienna (VC) has been a member of the Vermont Oxford Neonatal Network (VONN) since 1994. During the period 1994--2002, important differences between the VC and the VONN in both pre- and postnatal management and in late morbidities such as chronic lung disease (CLD) and severe retinopathy of prematurity (ROP) were observed. We hypothesize that stabilization of very-low-birth-weight (VLBW) infants on nasal continuous positive airway pressure (NCPAP) immediately after birth, combined with a restrictive use of artificial ventilation, might be responsible for lower rates of CLD and ROP. PATIENTS AND METHODS: Obstetric and neonatal data for all 1299 VLBW infants (401-1500 g) from the VC were compared with corresponding data for the 201,167 VLBW infants from the VONN for the period 1994--2002 with regard to respiratory management and patient outcome. Morbidity criteria were in accordance with VONN definitions. RESULTS: The percentage range for treatment and morbidity criteria for the VC and VONN are related to differences among various years within the observation period. Infants were stabilized at birth on NCPAP in 45-86% of cases in the VC vs. 37-63% in the VONN, the rate of mechanical ventilation was 40-59% vs. 66-74%, and use of surfactant was 31-50% vs. 55-64%. CLD was diagnosed in 14-32% of cases in the VC vs. 27-39% in the VONN, discharge on supplemental oxygen took place in 2-4% vs. 12-17% of cases and ROP (stages III and IV) was found in 1-10% vs. 8-12%. CONCLUSION: The association of lower rates of CLD and ROP in the VC compared to the VONN might be related to differences in early respiratory management of VLBW infants at high risk of development of respiratory distress syndrome. This needs to be confirmed in a large multicenter trial.

Dead-space washout by split-flow ventilation. A new method to reduce ventilation needs in premature infants.

OBJECTIVE: Chronic lung disease caused by volutrauma is one of the most important consequences of preterm delivery. In this pilot study a new method is presented that consists of flushing part of the dead space with fresh gas in order to reduce high tidal volumes, the chief cause of volutrauma. The aim of the study was to evaluate if the new method could reduce ventilatory effort in preterm infants by diminishing dead space. DESIGN AND SETTING: In split-flow ventilation, gas required for dead-space washout is split off from the regular ventilation circuit. The split flow bypasses the apparatus dead space and fills it retrogradely with fresh breathing gas, mainly in the pause between exhalation and inspiration. The mean per-minute ventilation and ventilation index after 12 h of conventional ventilation were compared with corresponding mean values after 12 h of split-flow ventilation in 17 preterm infants weighing <2,000 g. Statistical analysis was performed using the T -test for matched pairs. RESULTS: After switching from conventional ventilation to split-flow ventilation, the mean per-minute ventilation per kilogram of body weight decreased significantly from a mean value of 0.314+/-0.097 l/kg/min to 0.190+/-0.043 l/kg/min ( p <0.001), while the ventilation index decreased significantly from 28.47+/-7.48 to 16.10+/-4.13 ( p <0.001). CONCLUSION: Split-flow ventilation significantly reduces apparatus dead space during ventilation in preterm infants. This leads to reduced ventilatory effort.

Infantile sialic acid storage disease and protein-losing gastroenteropathy.

We report on a boy who presented at birth with gastroschisis and thereafter developed the characteristic clinical symptoms of infantile sialic acid storage disease within the first two months of life. Measurements of free sialic acid excretion (tenfold increase) in the urine and a 15-fold elevation of free sialic acid in cultured fibroblasts proved the diagnosis. The clinical course was complicated by hypertrophic cardiomyopathy, recurrent infections, hypothyroidism, and intestinal protein losses, which had never been described before in an infantile sialic acid storage disease patient. The child died at the age of 10 months. Clinical and laboratory findings are discussed and compared with other cases described in the literature.

Fatal air embolism in an extremely low birth weight infant: can it be caused by intravenous injections during resuscitation?

OBJECTIVE: A preterm infant with a birth weight of 384 g who succumbed to vigorous resuscitation for sudden respiratory failure on the third day of life is presented. Postmortem examination revealed, apart from extensive pulmonary hemorrhage, a fatal amount of air mainly in the right ventricle. We believe that this air had been introduced via peripheral venous cannulas due to inadvertent and unavoidable air admixture to each injection volume administered with a syringe, and we develop an experimental model to confirm that fatal amounts of air can indeed accumulate with frequent change over of syringes within a short period of time. DESIGN: An empty 50-ml syringe was connected to a 15-cm-long connection line via a three-way tap. With a 1 ml syringe 100 doses of 0.5 ml aqua were injected into the connection line. The amount of air which had collected in the 50 ml syringe after the 100 injection cycles was measured. This process was repeated three times each by three of the authors and the average air volume introduced with 100 injections calculated for each investigator. RESULTS: The average amounts of air which had entered the closed system after 100 acts of syringe assembly and aqua administration were 1.84, 1.95, and 2.0 ml. This corresponds to an average volume of almost 0.02 ml per injection.

Development and evaluation of VIE-PNN, a knowledge-based system for calculating the parenteral nutrition of newborn infants.

Calculating the daily changing composition of parenteral nutrition for small newborn infants is troublesome and time consuming routine work in neonatal intensive care. The task needs expertise and experience and is prone to inherent calculation errors. We designed VIE-PNN (Vienna Expert System for Parenteral Nutrition of Neonates), a knowledge-based system (KBS) in order to reduce daily routine work and calculation errors. VIE-PNN was redesigned several times because the clinicians accepted the system only when it saved time. The most recent version of VIE-PNN uses an Hypertext Markup Language (HTML)-based client-server architecture and is integrated into the intranet of the local patient data management system. Since more than 3 years all parenteral nutrition plans are calculated using VIE-PNN. Evaluating the system's performance and the users contentedness, we compared 50 nutrition plans calculated in parallel using VIE-PNN or a hand-held calculator, retrospectively analyzed more than 5000 nutrition plans stored in VIE-PNNs database and evaluated a user questionnaire. Nutrition plans were calculated in a mean time of 2.4 versus 7.1min using VIE-PNN or the hand-held calculator. Errors and omissions in the nutrition plans were detected in 22% versus 56% and errors in the VIE-PNN's plans occurring only with interactively changed values. Reviews of stored plans show that a mean of 4 out of 16 parameters were interactively changed. VIE-PNN was well accepted. Most important reasons for the successful operation of VIE-PNN in the daily routine work were time savings and robustness of the system.