bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Selenium Excretion in Infancy: Comparison between Term and Preterm Infants
Authors: Tsukahara Hirokazu , Deguchi Yoji , Hiraoka Masahiro , Hori Chikahide , Kimura Keiko , Kawamitsu Tooru , Konishi Yukuo , Kusaka Yukinori , Sudo Masakatsu
Published: October 2009

We evaluated the urinary excretion of selenium (Se), an essential component of glutathione peroxidase, in infants aged 1 week and 1, 4, and 7 months and examined the relationship between urinary Se and renal function. Daytime spot urine samples from a total of 80 infants were analyzed. The Se concentration in urine was measured by fluorometry, while the β2-microglobulin content, an index of renal tubular function, was determined by radioimmunoassay. In healthy term infants, the urinary Se excretion showed a peak level at 1 month of age. In contrast, the urinary Se concentration rapidly decreased in preterm infants from 1 week to 7 months postnatally. The level at 1 week in preterm infants was significantly higher than that in term infants, although the mean levels at 1 4, and 7 months were lower in preterm infants. The level of urinary Se did not correlate significantly with the β2-microglobulin concentration, either in term or preterm infants at any age investigated. Our results suggest that the renal excretion of Se probably reflects the body stores of Se and is not related directly to the renal function in infants. Urinary Se, a noninvasive marker of the Se status, may be used for diagnosis and follow-up of Se deficiency in infants.
Endocrine Regulation of Fetal Adipose Tissue Metabolism in the Pig: Ontogeny of Thyroxine Influence
Authors: Hausman D.B. , Hausman G.J. , Martin R.J.
Published: October 2009

Our previous studies indicated that thyroxine (T4) markedly enhanced adipose tissue development and metabolism when administered to hypophysectomized fetal pigs from days 70 to 90 of gestation. In this study, hypophysectomized (day 70) fetal pigs were implanted with T4 pellets, and blood and adipose tissue samples were obtained upon removal on days 73, 75, 80, or 85 of gestation to examine the time course of T4 response. T4 treatment in hypophysectomized fetuses resulted in an elevation in serum T4 levels by day 73 of gestation, with no further increase on day 80 or 85. Quantitative analysis of subcutaneous adipose tissue indicated that hypophysectomy per se had no influence on lipid deposition, whereas the extent of T4-stimulated lipid deposition increased with fetal age, beginning on day 75. Glucose oxidation and lipogenesis in subcutaneous adipose tissue slices was increased by T4 treatment in hypophysectomized fetuses by day 73 of gestation and further increased with additional time of treatment. Hypophysectomy per se induced a slight increase in lipogenesis only on days 80 and 85 of gestation. Basal lipolysis was unaffected by age, hypophysectomy, or T4 treatment. The responsiveness to a variety of lipolytic stimuli was both accelerated and enhanced by T4 treatment in hypophysectomized fetuses. These results indicate that the T4 influence on adipose tissue development (1) is already apparent following only 3 days of hormone treatment in the hypophysectomized fetuses, (2) clearly precedes hypophysectomy-induced alterations in cellular and metabolic development of adipose tissue, and (3) is not mediated exclusively by serum concentrations of the hormone.
Surface Tension Measurements on Pharyngeal and Tracheal Aspirate Samples from Newborns without and with Respiratory Distress Syndrome
Authors: Friedrich W. , Schmalisch G. , Haufe M. , Kling R. , Wauer R.R.
Published: October 2009

A rapid test determining surfactant deficiency or dysfunction might help in controlling therapy of respiratory distress syndrome (RDS). Forty tracheal aspirate samples (TA) from 40 newborns with RDS (group 1) and 46 pharyngeal from 46 newborns without RDS (reference group) were analyzed by surface tension measurement with the pulsating bubble surfactometer. Five surface tension parameters were compared. Marked differences between both groups could be noted for the parameters: minimum surface tension (γmin) and stability index (S), while maximum surface tension (γmax), surface tension after a 10-second adsorption period and hysteresis area did not have striking differences. The parameters γmin and S have the highest diagnostic value for determining surfactant deficiency or dysfunction. For a rapid test it is sufficient to compare γmin with reference values, because S is calculated from γmin and γmax.
Effects of Cordocentesis on Inferior Vena cava Velocity Waveforms: Differences between Normally Grown and Growth-Retarded Fetuses
Authors: Capponi Alessandra , Rizzo Giuseppe , Rinaldo Donatella , Arduini Domenico , Romanini Carlo
Published: October 2009

The objective of this study was to analyze the effects of cordocentesis on velocity waveforms recorded from the inferior vena cava and to evaluate differences, if any, in the hemodynamic response between normally grown and growth-retarded fetuses. Twenty-five normally grown fetuses and 20 growth-retarded fetuses were considered for this study. This latter group was characterized by abnormal Doppler indices in the umbilical artery and the middle cerebral artery suggestive of uteroplacental insufficiency as the causative factor of the impaired growth. Flow velocity waveforms were measured from the inferior vena cava immediately before and after cordocentesis and the % reverse flow during atrial contraction calculated. In normally grown fetuses the % reverse flow values did not vary significantly after cordocentesis, while in growth-retarded fetuses this index increased significantly after the procedure (p < 0.001). Furthermore, the amplitude of this increase was inversely related to pH levels in umbilical vein (p = 0.004). In conclusion, in growth-retarded fetuses cordocentesis induces an increase of % reverse flow in the inferior vena cava, while no modifications occur in normally grown fetuses. This suggests the presence in growth-retarded fetuses of an impaired cardiac adaptive mechanism to cordocentesis that may explain the higher incidence of complications occurring in such fetuses.
Impact of Central, Obstructive and Mixed Apnea on Cerebral Hemodynamics in Preterm Infants
Authors: Jenni Oskar G. , Wolf Martin , Hengartner Markus , von Siebenthal Kurt , Keel Matthias , Bucher Hans-Ulrich
Published: October 2009

The objective of this study was to evaluate the effect of central, obstructive and mixed apnea on cerebral total hemoglobin concentration (tHb), which is analogous to cerebral blood volume, and to investigate whether tHb alterations correlate with bradycardia and arterial desaturation. Measurements were carried out on 17 preterm infants (gestational age 26–30 weeks) with frequent apneic events. Near infrared spectrophotometry (NIRS) was used to quantify changes in tHb. Respiration was monitored by chest movements using impedance pneumography and by nasal airflow using a thermistor. In addition, heart rate, arterial oxygen saturation in each infant and esophageal pressure in 3 babies were continuously recorded. 130 apneic episodes of > 10 s duration showed four different patterns of tHb alterations: (1) no change in tHb (28%); (2) isolated decrease (35%); (3) isolated increase (12%), or (4) both combined, an initial decrease followed by an increase over the previous baseline level (25 %). Obstructive apneic episodes were associated with a significantly greater maximum fall in tHb (median 11.5; 5th percentile 0 and 95th percentile 30.5 μmol/l) compared to mixed (4.9, 0 and 26.4 μmol/l) and central events (3.0, 0 and 14.0 μmol/l). Changes in tHb correlated with heart rate only in purely central apnea and were not reflected in arterial oxygen saturation in any type of apnea. Obstructive apnea was observed to have the strongest impact on tHb. As these tHb alterations may exacerbate or cause intraventricular hemorrhage, efforts must be made to prevent obstruction of upper airways and to focus monitoring on cerebral perfusion.
Ontogeny of Circulating Leucocytes in the Fetal Guinea Pig
Authors: Jones Amanda C. , Burdge Graham C. , Warner Jill A. , Postle Anthony D. , Warner John O.
Published: October 2009

The ontogeny of leucocytes in the fetal guinea pig was investigated. The total leucocyte concentration increased between days 40 and 56, but thereafter was unchanged at term (day 68). T and B lymphocytes were detected on day 56 and at term, and while T cell concentrations remained constant between day 56 and term, the concentration of B cells decreased. The ratio of CD4+ to CD8+ T cells increased from 0.9 on day 56 to 3.0 at term. All fetal cell concentrations were significantly lower as compared with adult animals. The fetal peripheral blood mononuclear cell proliferative responses to mitogenic stimulation increased from day 40 to 56, but tended to decrease between day 56 and term. The fetal proliferative responses were signficantly lower as compared with adults. Comparison of these data with previous analyses of the pattern of human fetal lymphocyte development indicated that, although there were similarities, such as the timing of the first appearance of circulating lymphocytes, there were also differences, for example the changes which occur between birth and adulthood, between the two species. This suggests that the guinea pig may have a limited use as a model of some aspects of the ontogeny of the human immune system.
Effects of Different Surfactant Preparations on Bacterial Growth in vitro
Authors: Neumeister B. , Woerndle S. , Bartmann P.
Published: October 2009

Several lines of evidence suggest that surfactant and surfactant proteins may have direct effects on inhaled bacteria and are able to interact with lung defence mechanisms in many ways. We examined the effect of three different surfactant preparations (Alveofact®, Survanta® and Exosurf®) approved for treatment of the infant respiratory distress syndrome on different strains of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus agalactiae which are important neonatal pathogens and on Legionella pneumophila serogroup 1 as a frequent cause of pneumonia in adults. Addition of Survanta to saline seemed to delay the reduction of viable bacteria in sterile saline and induced a considerably accelerated growth of all examined E. coli strains. As opposed to this, addition of surfactant did not influence the kinetics of bacterial growth in brain-heart infusion or buffered yeast extract both with the exception of Exosurf which exerted an inhibitory effect on the multiplication of group B streptococci. Though the exact mechanisms underlying these effects remain to be determined, the influence of surfactant therapy on the growth of bacteria within the respiratory tract should be taken into account.
Changes in Cerebral Hemodynamics and Oxygenation during Hypothermic Cardiopulmonary Bypass in Neonates and Infants
Authors: Van Bel Frank , Zeeuwe Petra E.M. , Dorrepaal Caroline A. , Benders Manon J.N.L. , Van De Bor Margot , Hardjowijono Rudy
Published: October 2009

Delay in development after open-heart surgery in infants has frequently been reported. Inadequate brain perfusion and oxygenation during deep hypothermic cardiopulmonary bypass (CPB) may play an important role. We investigated the effect of CPB on cerebral perfusion and oxygenation in 12 neonates and infants (age 0–11 months) undergoing open-heart surgery. Changes in cerebral blood volume (ΔCBV; in ml/100 g brain tissue) and oxidation level of the intracerebral mitochondrial enzyme cytochrome aa3 (ΔCytaa3; in µmol/l) were measured with near infrared spectroscopy. Nasopharyngeal temperature (Tnas) for assessment of changes in brain temperature, and mean arterial blood pressure (MAP) were monitored continuously. CBV lowered during cooling and increased during rewarming. These changes were only related with changes in Tnas (p < 0.001; 0.07 ml·100 g-1/°C). No relation was found with changes in MAP or pump flow rate of the heart-lung machine. During steady-state hypothermic CPB, changes in CBV were only related to changes in MAP (p < 0.001). The individual regression lines between ΔCBV and MAP became steeper at lower absolute Tnas. Cytaa3 showed an increase shortly after the initiation of CPB in 9 patients, with a sustained decrease to baseline values in 8 patients towards the end of the CPB period. Two patients who had a circulatory arrest during CPB had a sharp decrease in Δcytaa3 after cessation of the heart-lung pump and showed no complete recovery of ΔCytaa3 to baseline at the end of the CPB period. We conclude that changes in CBV during CPB are related to changes in Tnas. During deep hypothermic steady-state CPB, changes in CBV and MAP were related to each other, suggesting lack of cerebral autoregulation. The large decrease in Cytaa3 in 2 patients with circulatory arrest suggests that this procedure compromises energy metabolism of the brain cell.
Immunologic Parameters in Cord Blood Indicating Early-Onset Sepsis
Authors: Lehrnbecher Thomas , Schrod Lothar , Rutsch Petra , Roos Thomas , Martius Joachim , von Stockhausena Hans-Burckhard
Published: October 2009

Different immunologic parameters were measured in cord blood to test their usefulness in the early diagnosis of early-onset sepsis. Cord blood levels of circulating intercellular adhesion molecule-1 (cICAM-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly elevated in septic compared to nonseptic neonates. No significant difference between either population was seen for cord blood C3a and elastase-α1-proteinase inhibitor complex (Eα1PI). Measured concentrations of cICAM-1, IL-6 and IL-8 in fetal and maternal blood did not correlate, indicating that the neonate’s response to sepsis is clearly different from the mother. Our data suggest that cord blood measurements of cICAM-1, IL-6 and IL-8 might be useful in identifying neonates with early-onset sepsis.
Measurement of Methemoglobin after EMLA® Analgesia for Newborn Circumcision
Authors: Law Rebecca M.T. , Halpern Stephen , Martins Rui F. , Reich Herman , Innanen Veikko , Ohlsson Arne
Published: October 2009

A statistically significant (p = 0.049) increase in methemoglobin (MetHb), which did not exceed normal values, was noted 8 h after application of 1 g of EMLA® (Eutectic Mixture of Local Anesthetics) to the foreskin of 10 normal newborns to reduce pain associated with circumcision. The highest MetHb concentration observed was 3 g/l (toxic > 50 g/l). No infant showed clinical signs of methemoglobinemia. We conclude that EMLA® is safe to use as a local anesthetic in term neonates.
Compartmental Study of Rat Renal Prostaglandin Synthesis during Development
Authors: Fernandez-Tomé María del Carmen , D’Antuono Cecilia , Kahane Veronica L. , Speziale Emir H.S. , Sterin-Speziale Norma B.
Published: October 2009

The biosynthesis of prostaglandins (PGs) from the endogenous and exogenous precursor, arachidonic acid (AA), in renal papilla, medulla and cortex from neonatal to adult rats was investigated. Rat renal papilla and medulla incubated in the presence of [1-14C]AA released radioactive PGE2, PGF2α and PGD2 which increased with age. No radioactive prostaglandins were found in the supernatants of renal cortex at any age studied. The amount of total prostaglandins released from the endogenous precursor also increased from 10 to 70 days of age, PGD2 being the prostaglandin that showed the most important rise. In the cortex, only PGE2 release increased with age. Cyclooxygenase (COX) activity was measured in papillary, medullary and cortical homogenates by using [1-14C]AA as substrate. Papillary and medullary COX activity increased after 10 days of age and continued to rise up to day 30 thereafter remaining unaltered until adulthood. Cortical COX activity was very low and decreased with age. These findings indicate the low capacity of the neonatal rat kidney to synthesize PGs.
Unapparent Systemic Dissemination of Mycobacterium tuberculosis
Authors: Jarreau Pierre-Henri , Delacourt Christophe , Poved Jean-Dominique , Cieuta Cécile , de Blic Jacques , Scheinmann Pierre
Published: October 2009

A healthy 6-week-old girl exposed to tuberculosis presented a positive DNA amplification for Mycobacterium tuberculosis complex in gastric aspirates and cerebrospinal fluid whereas she had no other clinical or biological symptoms. Cultures were negative. This report underlines the interest of polymerase chain reaction for early diagnosis of tuberculosis and suggests the importance of treating exposed neonates and young infants just as active tuberculosis.
Fifty-Hertz Magnetic Field Exposures of Premature Infants in a Neonatal Intensive Care Unit
Authors: Aasen Svein Erik , Johnsson Anders , Bratlid Dag , Christensen Terje
Published: October 2009

In this study the magnetic flux density in and around incubators of a neonatal intensive care unit was registered and mapped. The mean 50-Hz magnetic flux densities in an incubator were typically in the range of 0.2–1 μT, with maximum values around 1.5 μT. For 1 incubator, harmonics contributed to the field substantially. The field levels varied depending on the type of equipment, the positioning of the electronics and the position of the 240-volt main plugs. The positioning of the infant in the incubator and the precise mattress position in the incubator affected the magnetic flux density to a great extent, as did the positioning of the electronic monitoring and treatment equipment. The flux density values found were fairly low as compared to magnetic field levels present at some work places where high electric currents are used. In intensive care units, however, the duration of exposure can be very long, especially for premature infants. The fields can also be compared with the magnetic field levels of residences and are then approximately 100 times higher. Further studies are necessary – it seems important to record magnetic fields and attempt to reduce the levels. Such a reduction can be achieved by reducing the field from the incubators but also by changing the electronic equipment around the incubators or increasing the distance to the incubator. Further research should of course also study any mechanism by which magnetic fields can affect cells and organisms. Compared to the risks many of these infants are exposed to, it is difficult to say whether the magnetic field levels measured can represent a significant additional risk factor. However, this is an area where one should adopt a prudent avoidance strategy, particulary considering how easily these fields can be reduced, mainly through redesign of the various equipment.
Neither Motor Responses nor Gastric Emptying Vary in Response to Formula Temperature in Preterm Infants
Authors: Anderson Craig A. , Berseth Carol L.
Published: October 2009

The purpose of this study was to assess gastrointestinal responses to formula temperature in preterm infants. Healthy preterm infants were fed 4,250 KJ/1 formula at 6, 24, and 37° C. There was no significant difference in the magnitude of antral or duodenal motor responses among the three temperatures. All infants emptied approximately one third of the bolus feeding by 20 min, but there was no difference among the temperatures. Approximately 10–20% of a bolus feeding remained in the stomach 2 h postprandially, but there was no difference among the temperatures. Thermoreceptors do not appear to be functionally present in the preterm infant, suggesting that the benefit of feeding warmed formula to the preterm infant my have a limited physiological value.
Respiratory Support, Surface Activity and Protein Content during Nosocomial Infection in Preterm Neonates
Authors: Griese Matthias , Westerburg Bettina , Potz Christiane , Dietrich Petra
Published: October 2009

Small volume bronchoalveolar lavages from 10 infants (26.6 ± 0.4 weeks gestational age) during postnatal nosocomial infection were fractioned by differential centrifugation into large (LA) and small (SA) surfactant aggregates. Before deterioration of the clinical status, the surface tension at minimum bubble radius (γmin), as measured in a pulsating bubble surfactometer, was reduced to about 14 mN/m by LA and to about 22 mN/m by the corresponding SA. The γmin of both LA and SA increased during clinical deterioration, was highest at the worst clinical state and returned during recovery to values in the range before deterioration. Respiratory support significantly correlated to γmin at all times. In contrast, no correlation was observed for total protein or albumin content of the LA or SA fractions. The SA fraction was characterized by a 10-fold higher protein content than LA. These data demonstrate functional impairment of surfactant in subfractions during mechanical ventilation and nosocomial infection in preterm neonates that are not fully explained by inhibition with increasing amounts of total protein.
Characterization and Developmental Aspects of Anoxia-Induced Gasping in the Rat
Authors: Gozal David , Torres José E. , Gozal Yair M. , Nuckton Thomas J.
Published: October 2009

With increasing postnatal age, mammals display diminished tolerances for prolonged exposures to severe oxygen deprivation. Similarly, duration and efficiency of gasping, a unique mechanism for enhancing survival after anoxia-induced apnea, are also affected by postnatal age. We hypothesized that maturational patterns of anoxia-induced gasping may encompass more than a single monophasic phenomenon. Each of the putative phases of the gasping response may underlie unique characteristics which could be of relevance to survival capability. To study these issues, adult rats and rat pups at 2–3, 5, 10, 15, and 25 days of age underwent anoxic exposures with 100% N2 in a barometric chamber. In pups aged < 25 days but not thereafter, following an age-dependent period of central apnea, an initial gasping phase characterized by vigorous and frequent periodic bursts of a large inspiratory effort preceded and followed by expiration excursions emerged (phase I). This phase was followed by a period of relative respiratory silence of variable duration with occasional, interspersed phase I-like gasps (phase II). Finally, a third phase easily recognized by the onset of frequent inspiratory-only gasping efforts developed (phase III). The amplitude of phase III inspiratory gasps progressively diminished until their complete cessation. Although overlap between gasping phases was present, a marked age dependency in both duration and gasping frequency within each phase occurred. We conclude that anoxia-induced gasping responses in rat pups < 25 days old are triphasic in nature, exhibit defined phase-locked periodicities and respiratory effort patterns, and undergo significant maturation.
Bilirubin-Oxidizing Activity in Rat Brain
Authors: Ruud Hansen Thor Willy , Allen Jeffrey W.
Published: October 2009

Bilirubin may be cleared from the brain by transport across the blood-brain barrier and by a ‘sink effect’ into the cerebrospinal fluid. However, there is also evidence to suggest that bilirubin may be metabolized in the brain by a process of oxidation. The purpose of this study was to confirm the existence of bilirubin metabolism in the brain and to examine the possible contribution of such an activity to the bilirubin staining pattern characteristic of kernicterus. Mitochondrial membrane fractions were prepared in 0.32 M sucrose from whole rat brains as well as brain regions. The change in optical density of a bilirubin solution at 440 nm was measured over time following addition of the mitochondrial suspension. Our results confirmed the existence of a bilirubin-metabolizing activity in brain mitochondrial membranes. This activity could be removed by heating the mitochondrial suspension and had a definable temperature and pH maxima. The rate of oxidation of bilirubin ranged from 109 to 164pmol/min/mg protein. There were significant differences between rat brain regions in the ability to oxidize bilirubin. However, these differences could not explain the kernicterus staining phenomenon, because the highest activities were found in brain regions which are more heavily stained in kernicterus. We conclude that bilirubin is metabolized by brain mitochondrial membranes at a rate that would appear to represent a biologically meaningful contribution to bilirubin clearance from the brain. In the present model, differences in such an activity between brain regions do not appear to be compatible with a kernicteric staining pattern.
Plasma and Cerebrospinal Fluid Hyperinsulinism in Asphyxiated Piglets
Authors: Ábrahám Csongor S. , Temesvári Péter , Kovács József , Schultz Károly , Molnár Dénes
Published: October 2009

Insulin (I) plays a crucial role in the maturation of the perinatal brain, and it may also be involved in the pathogenesis of neonatal brain injuries. The aim of the present study was to reveal the effect of neonatal asphyxia on the regulation of I and glucose (G) metabolism in plasma and cerebrospinal fluid (CSF) in newborn piglets. The I concentrations were measured by radioimmunoassay, while the G levels were analyzed by the G oxidase method during three phases (basal, critical, recovery) of bilateral pneumothorax in newborn piglets. We observed a significant hyperinsulinism (p < 0.001) both in plasma and CSF and a mild hypoglycemia (p < 0.05) during the recovery period. Postasphyxial G infusion (1.1 M, 10 ml·kg––1) amplified the hyperinsulinism. The IcsF/piasma ratio (mean ± SEM; n = 16) was decreasing during cardiovascular failure (0.09 ± 0.02; NS) as compared with the initial value (0.12 ± 0.04), then it returned to basal values by 60min (0.14 ± 0.04; NS), and increased significantly 180min (0.40 ± 0.14; p < 0.05) after resuscitation of the piglets. There was a similar increase in GcsF/piasma ratio in asphyxiated animals at the end of experiments (0.99 ± 0.15 vs. initial 0.76 ± 0.05; p < 0.05). In conclusion, neonatal asphyxia resulted in plasma and CSF hyperinsulinism which may alter hypoxic-ischemic cerebral damages.
Plasma Somatostatin and Cholecystokinin Levels in Preterm Infants during the First Day of Life
Authors: Törnhage Carl-Johan , Serenius Fredrik , Uvnäs-Moberg Kerstin , Lindberg Tor
Published: October 2009

Our knowledge about regulatory gut peptides in preterm infants is scanty. We therefore began a study of plasma somatostatin (SS) and cholecystokinin (CCK) in preterm infants at birth and during the neonatal period. Plasma SS and CCK levels were assessed in 77 mothers and in 91 preterm infants immediately after birth (umbilical cord) and during the first day of life (IF) (n = 69, median age 5 h). The gestational age ranged from 23 to 36 weeks and the birth weight from 460 to 3,350 g. After Sep-Pak C18 semichromatography of plasma, SS and CCK were analyzed by RIA. Both plasma SS and CCK levels increased significantly during the first hours of life. Plasma SS levels were negatively correlated to gestational age, birth weight and birth length. When the SS-1F levels were adjusted for gestational age in a multivariate analysis there was no independent association with birthweight but a weak association with birth length. Plasma CCK-1F levels were not correlated with any of these variables. Plasma SS-1F levels were lower after cesarean section. Plasma SS and CCK levels during the first day were not correlated to multiple birth, mode of anesthesia, umbilical pH, Apgar score and blood glucose level before first meal.
Mid- and Long-Term Outcome of 89 Premature Infants Weighing Less than 1,000 g at Birth, All Appropriate for Gestational Age
Authors: Monset-Couchard M. , de Bethmann O. , Kastler B.
Published: October 2009

Objective: Advances in obstetrical and neonatal care have achieved dramatic reductions in the mortality of extremely low birth weight infants, but concerns regarding the long-term neurodevelopmental prognosis have increased. The study was performed to assess the physical and neurodevelopmental status of premature infants weighing < 1,000 g at birth who were appropriate for gestational age (AGA). Methods: A follow-up study including school level, physical and developmental examination and/or interviews of parents, pediatricians, teachers and social workers was carried out from January 1, 1981 to December 31, 1991, on 176 subjects who had been AGA premature neonates weighing < 1,000 g and were admitted to the Port Royal Neonatal Intensive Care Unit. Eighty-nine survived (50 girls, 39 boys). Five children were lost to follow-up after 3 years of age. Neurological sequelae, developmental and/or intellectual quotients, school level and results, vision, hearing, language, weight, height, and behavior were evaluated. Results: At the last evaluation, 37% of children were completely normal (24% had always been normal); 52% were normal in the 4th year of life, decreasing to 31% in the 8th year. Minor disabilities increased from 31% in the 4th year to 53% in the 8th year. Moderate disabilities ranged yearly between 8 and 14%. Five children had major handicaps diagnosed before 3 years of age (4 cerebral palsies following severe neonatal brain lesions and 1 severe retardation with renal dwarfism). No difference was found between children with or without bronchopulmonary dysplasia. Twelve children (14%) had hearing loss (3 deafness) and 27 (32%) had visual deficits (no blindness). Nursery school begins at 3 for French children: 86% of the followed survivors were at nursery school at 3 years of age, 74% of 6-year-olds were in the first grade, primary school, and 50% of 7-year-olds were in second grade. Half the children with high socioeconomic/cultural risks had some school difficulties. Similar results were collected from various cross-sectional studies in the recent literature. Conclusions: While 20% of the children had moderate to severe disabilities, an increasing number of minor deficiencies appeared with age. Socioeconomic/cultural factors had a deleterious effect even in structurally normal children, but they had an even worse effect in children with minor deficiencies, owing largely to the frequent lack of proper management at home.
Microvascular Pressures in Isolated Perfused Immature Lamb Lungs: Effects of Flow Rate, Left Atrial Pressure and Surfactant Therapy
Authors: Matsuda M. , Anderson-Morris J. , Raj Usha
Published: October 2009

To determine the effect of some physical factors on microvascular pressures in immature lungs, we studied the lungs of 125-day gestation immature lambs (term 150 days). Lambs were delivered and ventilated for 30 min prior to isolation of the lungs. Nine had surfactant (Survanta, 100 mg/kg) instilled into the lungs prior to delivery, and 7 did not (control group). Lungs were kept distended with airway pressure at 20 cm H2O and perfused with autologous blood, using a steady flow pump. Papaverine was added to the blood to eliminate vasomotion. We measured pulmonary artery and arterial, double and venous occlusion pressures, with flow at 100,200 and 260 ml·kg––1·min––1 and left atrial pressure (Pla) at 0, 10 and 15 mm Hg. We found that the vascular pressure profile was similar in control and surfactant-treated lungs under similar conditions of flow and Pla. Our data show that elevation of Pla results in significant increases in capillary (double occlusion) pressure; however, the preterm lung accommodates increases in flow with little change in capillary pressure. An increase in flow rate in the presence of elevated Pla had the greatest effect on capillary pressure. All lungs became hemorrhagic when capillary pressure exceeded 30 mm Hg. We speculate that in preterm infants, stress failure of pulmonary capillaries and hemorrhage will occur when there is marked elevation of capillary pressures resulting from increased blood flow in the presence of pulmonary venous constriction or left ventricular dysfunction.
Risk Factors of Sensorineural Hearing Loss in Preterm Infants
Authors: Borradori C. , Fawer C.-L. , Buclin T. , Calame A.
Published: October 2009

Among 547 preterm infants of ≤ 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.
Brain Stem Auditory-Evoked Response in Relation to Neonatal Glucose Metabolism
Authors: Cowett Richard M. , Howard Gia M. , Johnson Joanne , Vohr Betty
Published: October 2009

Imprecise control of glucose homeostasis is a hallmark of neonatal glucose metabolism. A relatively wide range of glucose concentrations is considered ‘euglycemic’ (2.22–6.94 mmol/l, 40–125 mg/dl) in the neonatal period. We investigated the effects of a wide range of glucose concentrations on brain stem conduction time (BCT) I-V interpeak latency or prolonged wave V latency. Neonates were assessed by brain stem auditory-evoked response followed immediately by heelstick sampling to determine the blood glucose concentration. Twenty-seven appropriate for gestational age (AGA) term neonates (birth weight 3,245 ± 766 g, mean ± SD; gestational age 39 ± 2 weeks) were studied 3.1 ± 3.7 days after birth. Twenty-three AGA preterm neonates (birth weight 2,175 ± 477 g; gestational age 35 ± 1 weeks) were studied 6.0 ± 7.2 days after birth. Brain stem conduction time wave I-V interpeak latency and wave V latency were determined in two trials using a Grason-Stadler ABR screener at a 60-decibel stimulation level in the right ear. Neonates were studied between 33 and 40 weeks gestational age. Although the blood glucose concentration ranged from 1.38 to 6.83 mmol/l (25–123 mg/dl), there was no correlation between either brain stem conduction time wave I-V interpeak latency or wave V latency and blood glucose concentration. We conclude that alterations in glucose concentration within the generally accepted neonatal euglycemic range do not effect the functional status of the brain stem auditory pathway. We suggest that the data can be interpreted to affirm that tighter clinical control of glucose homeostasis is probably not required in the neonatal period.
lnterleukin-1α Upregulates the Expression of Surfactant Protein-A in Rabbit Lung Explants
Authors: Dhar Vijay , Hallman Mikko , Lappalainen Urpo , Bry Kristina
Published: October 2009

Interleukin-1 (IL-1) is an important participant in infectious and inflammatory conditions. Interleukin-1 receptor antagonist (IL-1 ra) prevents the effect of IL-1. We have shown that injection of interleukin-1 α (IL-1α) into the amniotic fluid of pregnant rabbits stimulates the expression of surfactant protein-A (SP-A) in the lungs of the fetuses. We hypothesized that IL-1α similarly enhances the expression of SP-A in rabbit lung explants in vitro. Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth’s medium on a rotating platform in the presence or absence of IL-1α (5.7–570 ng/ml) or IL-Ira (1–10 μg/ml). Dibutyryl cAMP (1 mM) served as a positive control. After 3 days in culture, the explants were harvested and Northern analysis of SP-A was performed using the 1.9-kb rabbit SP-A cDNA probe. IL-1α and dibutyryl cAMP increased the expression of SP-A twofold, as judged by video densitometry. IL-1ra did not change SP-A expression as compared with controls, suggesting that endogenous IL-1 activity was not responsible for the basal level of SP-A expression in the explants. Dibutyryl cAMP increased the expression of SP-B mRNA, whereas IL-1 α had no effect on SP-B mRNA concentration. We conclude that inflammatory mediators interact with lung cells to alter synthesis of important components of the surfactant system.
Effect of Fetal Nephrectomy on Insulin-Like Growth Factors and Their Binding Proteins in Sheep
Authors: Iwamoto Harriet S. , McConnell Carol J.
Published: October 2009

Bilateral nephrectomy retards fetal growth and decreases somatomedin (insulin-like growth factor-I, IGF-I) activity. To determine whether nephrectomy alters the synthesis of IGF-I or its binding proteins (IGFBPs), we studied 6 sets of twin fetuses. Kidneys were removed bilaterally from 1 twin of each set at 112–122 days of gestation (term 145 days). Plasma IGF-I concentrations were greater in nephrectomized fetuses than in the intact twins during the 1st week (261 ± 35 vs. 153 ± 21 ng/ml, p < 0.02; mean ± SE) but not the 2nd week after surgery. Nephrectomy increased the abundance of the IGFBPs to levels 2–3 times greater than those in intact twins. Fetal hepatic IGFBP1 mRNA levels increased in 4 of 6 nephrectomized fetuses, while those of IGF-I, IGF-II, IGFBP2 were unchanged. Nephrectomy markedly alters the abundance of IGF-I and IGFBPs in plasma probably through mechanisms unrelated to synthesis.
Reticuloendothelial System Uptake of Infused 125l-Trypsin in Newborn and Adult Rats
Authors: Levine Jeremiah J. , Pettei Michael J.
Published: October 2009

Previous studies have demonstrated enhanced intestinal trypsin uptake and decreased liver clearance of trypsin in newborn rats compared to adults. In order to examine the effectiveness of the reticuloendothelial system (RES) in clearing trypsin, bovine trypsin (1.25 mg/l00 g body weight) plus trace 125I-trypsin were injected into the portal vein of 2-week-old (n = 57) and adult (n = 44) control rats or following RES stimulation using intraperitoneally injected lipopolysaccharide or RES suppression with intraperitoneally injected oleic acid emulsion. Plasma, liver and spleen 125I activities were assessed at 1 5 or 15 min following infusion in control, stimulated and suppressed animals. Newborn control rats had significantly increased 125I plasma levels with decreased liver and spleen 125I activity compared to control adults. RES stimulation in the newborns did not lead to any change in liver or plasma levels although splenic values increased while adults had a decrease in liver 125I activity. RES suppression in the newborns led to increased plasma and decreased spleen 125I-trypsin values while adult rat levels were unchanged. The immature reticuloendothelial system in newborns is poorly responsive to RES stimulation although it can be made even further inefficient by RES suppression. The combination of RES immaturity and lack of response to stimulation may make newborns susceptible to proteolytic damage, especially during times of increased systemic levels of proteolytic enzymes.
Enhancement of Central Noradrenaline Release during Development Alters the Packing Density of Neurons in the Rat Occipital Cortex
Authors: Ruiz Samuel , Fernández Victor , Belmar Jorge , Hernández Alejandro , Pérez Hernán , Sanhueza-Tsutsumi Miguel , Alarcón Sergio , Soto-Moyano Rubén
Published: October 2009

The effect of chronic yohimbine treatment early in life on packing density of neurons was evaluated in the occipital cortex of young rats. Yohimbine administration to pups between days 5 and 16 of postnatal life (2.5 mg/kg/day i.p.) resulted at 45 days of age in significantly higher neuronal density in layers II–V of the occipital cortex, the effect being more marked in the dorsal region than in the dorsolateral and lateral ones. Results suggest a relationship between enhanced central noradrenaline activity and altered development of the neuropil in the occipital cortex.
Use of Antibodies against the Human Antigen of Erythroblasts for the Detection of Nucleated Erythrocytes in the Maternal Circulation
Authors: Savion Shoshana , Carp Howard , Shepshelovich Jeanne , Irlin † Joseph , Kostykov Michael , Fein Amos , Toder Vladimir
Published: October 2009

In the present study, we tried to detect nucleated erythrocytes in maternal blood by means of the HAE9 antibody that binds to the antigen of erythroblasts (Ag-Eb) on nucleated erythroid cells. Umbilical cord blood and placental cells, which are known to contain a high number of nucleated erythrocytes, indeed demonstrated a high percentage of Ag-Eb-positive cells. In comparison, HAE9 stained up to 4.5% of the peripheral blood cells collected from pregnant women, but not those of nonpregnant women or normal men. These results, demonstrating a simple and reliable method for the identification of nucleated erythrocytes in the maternal circulation using the anti-Ag-Eb antibody, might open new possibilities for the detection of nucleated erythrocytes in maternal blood.
Behavioral Teratogenesis: An Extension to the Teratogenesis of Functions
Authors: Auroux Maurice
Published: October 2009

Major malformations correspond to pathology during the first 2 months of gestation. Thereafter, histological and biochemical abnormalities can result from different negative maternal incidents and, without obvious malformations, change the phenotype of the conceptus. These abnormalities lead to essentially functional disorders often compatible with life and to more or less serious handicaps. All systems, when they arrive at such a stage of development, can be theoretically involved. The central nervous system (CNS) offers a very clear example of such weaknesses because its maturation is particularly long and susceptible to changes even after birth. The steps of this maturation overlap and form a continuum reflected in the pathology. Mental retardation occurring in children born of mothers who were subjected to atomic radiation, or ingested methylmercury from industrial waste, or who suffered the effects of lead, alcohol or tobacco constitutes a clear clinical example. Animal experiments confirm these data, adding pathogenic explanations. These experiments also explore the possible consequences that some medical techniques such as modern reproductive technology, for example embryo freezing, can have on the development of the conceptus. Toxic substances or drugs can also be responsible for such abnormalities through a genetic attack on spermatogenesis. Behavioral teratogenesis also opens a larger persepective related to the optimal quality of the conceptus and the determining factors, from stress or dietary factors during apparently normal pregnancy to paternal age at the moment of conception. Finally, given that other systems than the CNS can be involved in histological or biochemical abnormalities, such as the reproductive system, we must ask what other types of functional pathology can be induced by interventions on gametes, the embryo and the fetus. Thus, behavioral teratogenesis leads to the teratogenesis of functions.
Visual Evoked Potentials for Prediction of Neurodevelopmental Outcome in Preterm Infants
Authors: Ekert Paul G. , Keenan Nancy K. , Whyte Hilary E. , Boulton Jill , Taylor Margot J.
Published: October 2009

Visual evoked potentials (VEPs) have proved to be accurate predictors of outcome in term infants with hypoxic-ischemic encephalopathy. Parallels between term asphyxia and hypoxic-ischemic injury in the preterm brain suggested the hypothesis that VEPs may predict the development of periventricular leukomalacia (PVL) and later cerebral palsy. 123 infants less than 32 weeks’ gestational age were enrolled in the study. VEPs were done in the first 3 weeks of life (usually first week). VEPs did show a statistically significant association with PVL (p < 0.04) although false-positive recordings were twice as frequent as true-positive recordings. VEPs were not associated with grade III–IV intraventricular hemorrhage (p = 1.0). Unlike asphyxiated term infants, VEPs were not predictive of abnormal neurodevelopmental outcome in the preterm population.
Beneficial Effect Induced by a Beta-Adrenoceptor Blocker on Fetal Growth in Streptozotocin-Diabetic Rats
Authors: Clabaut M. , Stirnemann B. , Bouftila B. , Robert I.
Published: October 2009

Treatment by a β1,β2-adrenoceptor antagonist has been much used during pathological pregnancies. These agents can reduce the oxygen consumption of the myocardium, increase the coronary blood flow towards ischemic heart areas and improve return of venous blood flow towards the heart. The aim of this study was to determine the mechanism of action of this agent and to investigate whether a total β-adrenoceptor antagonist could reduce the fetoplacental disorders elicited in streptozotocin-diabetic pregnant rats. Diabetes was engendered on day 7.5 of pregnancy, and the animals were studied on day 21. Untreated nondiabetic rats or nondiabetic rats treated with propranolol, a total β-adrenoceptor blocker (2 mg kg––1/day, i.p.), had a healthy placenta without vascular disturbances, with normal arterial blood velocity in the uterine artery, placenta, umbilical cord and fetal aorta, and showed eutrophic fetuses (3.9 ± 0.0 g, mean ± SEM). Untreated diabetic rats had severe placental lesions, with a reduction of arterial blood velocity in the uterine artery (p < 0.01), placenta (p < 0.01) and umbilical artery (p < 0.05), and exhibited fetal hypotrophy (2.3 ± 0.1 g, mean ± SEM, p < 0.001) compared with nondiabetic untreated rats. Treatment of diabetic rats with propranolol (2 mg kg––1/day, i.p.) enhanced fetal weight (3.66 ± 0.2 g) and slightly increased fetal insulin secretion, restored arterial blood velocity to control values in the uterine artery and fetal aorta and reduced placental lesions. In conclusion, our results suggest that the beneficial effects of propranolol were at least in part related to an improvement of uteroplacental hemodynamics; it induced a better redistribution of the blood towards the placenta and the fetal systemic circulation. Propranolol treatment could protect cell membranes against free oxygen radicals and lipid peroxidation, involved in the pathogenesis of ischemic injury in diabetes.
Testing Surfactant Treatment Responses: A Comparison of Two Models
Authors: Henry Michelle D. , Ikegami Machiko , Jobe Alan H.
Published: October 2009

We have compared treatment responses of two surfactants in two animal models of respiratory distress syndrome. Preterm rabbits at 27 days gestation and premature lambs at 126 days gestation were treated with natural sheep surfactant Survanta® (Ross Laboratories), or no surfactant and then were ventilated with the same ventilation style to achieve tidal volumes of 8 ml/kg. Dynamic compliances at 15 min were higher for control and surfactant-treated rabbits than for preterm lambs. Sheep surfactant and Survanta increased compliances in rabbits, but only sheep-surfactant-treated lambs had compliances higher than controls at 15 min of age. Maximal lung volumes (milliliters per kilogram) of the rabbits (after 15 min ventilation) were about twice those of the lambs (after 4 h of ventilation). Lung volumes of sheep-surfactant-treated rabbits were larger than for Survanta-treated rabbits, but no differences in lung volume were evident between the surfactant-treated lambs. The two models for testing surfactants do not give the same results when directly compared.
Fetal Encephalopathy after Maternal Anaphylaxis
Authors: Luciano Rita , Zuppa Antonio A. , Maragliano Giovanna , Gallini Francesca , Tortorolo Giuseppe
Published: October 2009

Fetal hypoxic-ischemic encephalopathy can be diagnosed at birth by means of cerebral ultrasound scanning. The morphological appearance of the lesions depends on the time elapsed between the insult and examination of the brain. We report a case of a neonate affected by multicystic encephalomalacia and corpus callosum atrophy attributable to an episode of maternal anaphylactic shock which occurred at 27 weeks of gestation following intravenous iron injection. The diagnosis was made by means of a cerebral ultrasound scan performed at birth and confirmed by magnetic resonance. This case demonstrates that maternal severe acute hypotension during pregnancy can cause fetal cerebral damage similar to the hypoxic-ischemic injuries occurring in the perinatal period.