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Biomedical subjects

M Obladen

Publications and source records attributed to M Obladen.

At least 91 records · Page 5Linked to original sources
PubMed1994

The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group.

BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.

Anemia, Neonatal↗
PubMed1994

Continuous monitoring of heart rate variability in preterm infants.

A method for continuous monitoring and recording of neonatal heart rate variability (HRV) and further physiological parameters in the intensive care unit is presented: 16 neonatal monitors were connected via two input/output processor boards to a personal computer. Patient data were processed by special software. Every day a 24-h record was printed for each infant, including a continuous registration of long-term (LTV) and short-term variability (STV) of heart rate along with baseline heart rate, respiratory rate, body temperature, temperature of the incubator and transcutaneous partial pressures of oxygen and carbon dioxide (tcPO2 and tcPCO2). For each parameter automatic artefact removal was implemented. Median and percentiles were computed once daily from all valid values. The influence of gestational and postnatal age and of respiratory distress syndrome (RDS) on HRV was studied in 105 preterm infants below 33 weeks of gestation during the first 7 days of life. An increase of both LTV and STV was seen with increasing gestational and postnatal age. In infants with RDS a decreased LTV was found in relation to the severity of the disease. HRV was also decreased in impaired brain function due to intraventricular hemorrhage, asphyxia or sedative treatment.

Computers↗
PubMed1994

Surfactant bolus instillation: effects of different doses on blood pressure and cerebral blood flow velocities.

Fifteen preterm infants suffering from respiratory distress syndrome were randomly allocated to receive either high-dose (200 mg/kg) or low-dose (100 mg/kg) surfactant treatment. Retreatments were done with the low dose. Blood pressure, blood gases and cerebral blood flow velocities were determined before and after 24 bolus instillations. With the high dose mean blood pressure and mean cerebral blood flow velocity dropped significantly. With the low dose only mean cerebral blood flow velocity decreased; the course was unrelated to blood pressure or PCO2 fluctuations. The mechanisms leading to the observed circulatory changes after surfactant instillation remain unclear.

Blood Flow Velocity↗
PubMed1994

L-selectin is down-regulated in umbilical cord blood granulocytes and monocytes of newborn infants with acute bacterial infection.

The leukocyte glycoprotein L-selectin mediates an early step in the recruitment of leukocytes to sites of inflammation. L-Selectin surface expression is rapidly down-regulated by inflammatory signals in vitro. In a prospective study, we found L-selectin expression on umbilical cord blood granulocytes and monocytes to be significantly decreased in newborn infants with acute bacterial infection compared with controls (p < 0.01). A significantly reduced L-selectin expression of both granulocytes and monocytes was also found to be associated with an increased neutrophil immature/total ratio (p < 0.01) but not with other laboratory markers of neonatal sepsis. There was no apparent impact of prematurity, low birth weight, gestational hypertension, or gestational diabetes on L-selectin expression. Although the mode of delivery did not affect granulocyte L-selectin expression, umbilical cord blood monocytes showed an increased L-selectin expression after emergency cesarean delivery compared with samples obtained after elective cesarean or vaginal delivery (p < 0.01). We conclude that acute systemic inflammation results in down-regulation of granulocyte and monocyte L-selectin expression in vivo similar to that observed in vitro.

Acute Disease↗
PubMed1994

Differences in morbidity and mortality according to type of referral of very low birthweight infants.

Maternal and social risk, prenatal and obstetric care, resuscitation and neonatal care in very-low-birthweight infants (VLBW) may vary with the type of referral. In 453 VLBW's (< 1500 g) admitted to our neonatal intensive care unit 1987-1992, we classified transport type as: A: No transport (n = 240), B: Maternal transport (n = 88), C: Infant transport (n = 125). Stepwise multiple discriminant function was determined for the identified factors. The risk of mortality was investigated by logistic regression analysis. In group A, mean maternal age was higher and mothers' social status lower than in groups B and C. In group B, infants were considerably smaller and less mature, but when adjusted for gestational age, suffered less frequently from RDS, obviously due to more frequent induction of lung maturation. In group C, less than half of the infants were resuscitated by a neonatologist. Infants of this group were frequently hypothermic at admission and required prolonged artificial ventilation more frequently. Total VLBW survival averaged 77%, increasing from 69 to 88% within the study period. Total rate of severe intraventricular hemorrhage was 4.8% in surviving infants. VLBW infants with different forms of referral differ in their inherent risk. After maternal transport they have less morbidity despite a higher grade of immaturity. Regionalization of perinatal care for these infants remains the greatest potential for further reduction in infant mortality.

Female↗
PubMed1994

Umbilical venous erythropoietin and umbilical arterial pH in relation to morphologic placental abnormalities.

OBJECTIVE: To investigate the relation between the biochemical markers of umbilical venous erythropoietin and umbilical arterial pH and morphologic placental abnormalities in fetal hypoxia. METHODS: Placentas from 300 high-risk newborn infants (gestational age 24-42 weeks) were examined macroscopically and microscopically following standardized criteria. The morphologic findings were correlated with the erythropoietin concentration in umbilical venous blood and with umbilical arterial pH at birth. Venous hematocrit and circulating nucleated red blood cells were measured in 112 of these infants during the first 6 hours of life. RESULTS: The umbilical venous erythropoietin concentration correlated significantly (r = 0.74) with the number of circulating nucleated red blood cells. In 26 placentas without morphologic abnormalities, the median (and 25th and 75th percentiles) erythropoietin concentration was 35.2 mU/mL (19.2-48.7) and umbilical arterial pH was 7.30 (7.20-7.33). The erythropoietin concentration was elevated significantly when placental examination showed evidence of acute villous circulatory disturbance (61.3 mU/mL; 24.2-125.1), fetal vasculopathy (85.6 mU/mL; 23.7-119.7), or chorioamnionitis with fetal reaction (51.3 mU/mL; 27.7-118.7). The erythropoietin concentration varied significantly with the stage of placental meconium phagocytosis; it was 62.7 mU/mL (16.3-125.9) if meconium phagocytosis was classified as recent, 128.2 mU/mL (44.4-1483.2) if it was classified as a few hours old, and 66.2 mU/mL (46.3-140.1) if it was classified as a few days old. Umbilical arterial pH was not altered significantly with different morphologic placental abnormalities. CONCLUSIONS: Fetal erythropoietin production is stimulated by hypoxia after a few hours' delay and leads to increased erythropoiesis. Placental examination combined with measurement of umbilical venous erythropoietin and umbilical arterial pH provides information about earlier fetal hypoxia.

Age Factors↗
PubMed1993

Diminished cord blood lymphocyte L-selectin expression in neonatal bacterial infection.

L-Selectin, a leukocyte surface glycoprotein involved in white blood cell extravasation, is rapidly down-regulated after leukocyte activation. We prospectively determined lymphocyte L-selectin expression in freshly obtained cord blood samples of 98 neonates (gestational age 25-42 weeks). In eight infants with bacterial infection, the mean percentage of L-selectin(high) lymphocytes was 32.5% (SD 20.1%), compared to 60.1% (SD 18.7%) in the control group (P < 0.01). A percentage of L-selectin(high) lymphocytes of less than 42% had a sensitivity of 75% and a specificity of 82% in identifying infected newborns. Cord blood lymphocyte L-selectin expression was independent of gestational age, birth weight, umbilical artery pH, hematocrit, white blood cell count, absolute neutrophil count, C-reactive protein level, or maternal fever before delivery while there was a weak correlation with the newborn's immature/total ratio and platelet count. To our knowledge, this is the first report demonstrating downregulation of human lymphocyte L-selectin expression following activation of the immune system in vivo.

Cell Adhesion Molecules↗
PubMed1993

Increased cerebral blood flow velocities in newborn infants of smoking mothers.

Cerebral blood flow velocities (CBFV) were measured by the pulsed Doppler method in 41 infants of smoking mothers and in 59 apparently healthy control infants. Although gestational age, birth weight, and systolic blood pressure were lower in infants exposed to tobacco smoke prenatally, systolic (65 +/- 11 vs. 47 +/- 12 cm/s, mean +/- SD; P < 0.001), mean (36 +/- 6 vs. 25 +/- 6 cm/s; P < 0.001), and diastolic (17 +/- 4 vs 13 +/- 4 cm/s; P < 0.001) CBFVs in the anterior cerebral artery were significantly higher when compared to control infants. Similar differences were seen in the internal carotid and in the basilar arteries. Multiple regression analysis did not reveal differences other than maternal smoking to explain these observations. We conclude that prenatal tobacco smoke exposure is related to increased CBFVs in newborn infants. Further studies should determine whether this relation is not only statistical but causal and whether increased CBFVs are an indicator of prolonged effects of prenatal tobacco smoke exposure.

Birth Weight↗
PubMed1993

Exposure of newborn infants to di-(2-ethylhexyl)-phthalate and 2-ethylhexanoic acid following exchange transfusion with polyvinylchloride catheters.

Infants in the neonatal intensive care unit are regularly exposed to the plasticizer di-(2-ethylhexyl)-phthalate (DEHP) following exchange transfusion or extracorporeal membrane oxygenation. Whether such exposure leads to increased morbidity is not known, although elevated levels of DEHP have been associated with necrotizing enterocolitis and cholestasis. The hypothesis that infants undergoing exchange transfusion are exposed to toxic levels of DEHP and the presumed metabolite 2-ethylhexanoic acid (EHXA) was tested by measuring serum levels of DEHP in 16 newborn infants (gas-liquid-chromatography) and urine concentrations of EHXA in 6 of these infants (gas chromatography-mass spectrometry). DEHP levels were undetectable (< 1 microgram/mL) before exchange but ranged from 6.1 to 21.6 micrograms per mL of serum (average, 12.5 +/- 6.2 micrograms/mL) after a single exchange transfusion. DEHP uptake did not result in cholestasis. EHXA peak levels were 127 to 416 ng per mL of urine, with a median of 174 ng per mL. Concentrations of EHXA were lower than anticipated, which indicates that EHXA is not a major metabolite in the neonatal infant.

Bilirubin↗
PubMed1993

Respiratory disorders of the neonate.

Respiratory disorders remain a major cause of neonatal mortality and morbidity. This review focuses on clinical trials and diagnostic procedures in neonatal respiratory disorders reported from October 1991 to September 1992. It leaves out animal studies, artificial ventilation techniques, extracorporeal membrane oxygenation, and follow-up studies. Surfactant substitution comes of age and first side effects of this successful treatment are described. Infection with ureaplasma urealyticum seems to contribute to chronic lung disease. The latter can be effectively treated with dexamethasone. However, because of numerous and severe side effects, this treatment requires scrupulous risk-benefit evaluation in each case.

Bronchopulmonary Dysplasia↗
PubMed1993

Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged rabbits are influenced by the instillation technique.

Surfactant bolus instillation has been reported to cause changes in arterial blood pressure (BP) and cerebral blood flow velocities which may increase the risk of intraventricular haemorrhage. To avoid these effects, slow tracheal infusion was evaluated as a possible alternative method of surfactant administration. Saline lung lavages were performed in 13 anesthetized and artificially ventilated adult rabbits to produce respiratory distress syndrome. Curosurf (CS, 200 mg/kg) labeled with 14C-dipalmitoyl-phosphatidylcholine (-DPPC) and/or red microspheres (RMS) was instilled into the trachea either as a single bolus (n = 8) or by infusion during 45 min via a side-channel within the wall of the tracheal tube (n = 5). An arterial cannula was placed for monitoring of blood gases and BP. To determine surfactant distribution, the lungs were cut into 60-70 pieces and radioactivity and/or the number of RMS were measured in each piece. The distribution of RMS was closely related to the distribution of 14C-DPPC (r = 0.96). Bolus instillation of CS led to a prompt and sustained increase in PaO2 (from < 10.5 to > 40 kPa within 2 min), a transient decrease in BP, and a reasonably homogeneous pulmonary surfactant distribution. Tracheal infusion of CS changed neither BP nor PaO2 during the observation period of 60 min. The pulmonary distribution of CS was extremely uneven after infusion. The distribution of exogenous surfactant and its effects on gas exchange are influenced by the instillation method. An inadequate instillation technique may add to the causes of "poor response" after surfactant replacement.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Cord blood erythropoietin in relation to different markers of fetal hypoxia.

OBJECTIVE: To investigate the relationship between erythropoietin concentration in umbilical venous blood and clinical signs of fetal hypoxia. METHODS: We measured erythropoietin concentrations in umbilical venous blood from 200 consecutively born neonates using an enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies. Results were available within 6 hours. Inter-assay variation was 8.5% and the mean intra-assay variation was 14.2%. RESULTS: Using a multiple regression analysis, we found that the erythropoietin concentration correlated significantly (P < .01) with fetal growth retardation and umbilical acidosis but not with gestational age, meconium-stained amniotic fluid (AF), abnormal fetal heart rate (FHR) pattern, or Apgar score at 5 minutes. Median erythropoietin concentrations were 25.1 mU/mL in infants with no risk factors or complications during pregnancy and delivery (n = 19), 25.8 mU/mL after complicated pregnancy (n = 95), 50.6 mU/mL with meconium-stained AF (n = 12), 44.7 mU/mL with abnormal FHR pattern (n = 40), 47.8 mU/mL with both stained AF and abnormal FHR pattern (n = 10), and 72.6 mU/mL with umbilical acidosis (n = 24). The median erythropoietin concentration increased significantly with decreasing pH and with increasing base deficit in umbilical arterial blood. The erythropoietin concentration in umbilical venous blood (cutoff value 50 mU/mL) discriminated between infants with no clinical signs of fetal hypoxia and those with umbilical acidosis with a sensitivity of 75% and a specificity of 90%. CONCLUSIONS: Elevated erythropoietin concentrations in umbilical venous blood indicate prolonged fetal hypoxia. The ELISA technique might be a useful tool for determining the exact time course of erythropoietin concentrations in fetal hypoxia.

Acidosis↗
PubMed1992

Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants.

Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants.

Barotrauma↗
PubMed1992

Surfactant protein A in the course of respiratory distress syndrome.

Surfactant-associated protein (SP-A) was measured in tracheal aspirates of ventilated infants with (n = 51) and without (n = 21) respiratory distress syndrome (RDS). SP-A concentrations in samples collected after birth were significantly lower in RDS than in infants ventilated for other reasons than RDS (median 0.03 vs. 1.60 micrograms/ml). As a biochemical test to diagnose RDS early after birth, the sensitivity of measuring SP-A in tracheal aspirates was 87% and specificity 81%. SP-A content in tracheal aspirates of infants with RDS was monitored during the first 7 days of life. A significant (P less than 0.001) increase within the first 4 days was found in those infants who survived, whereas no such change was found in those infants who died.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Normal auditory brain stem evoked responses in infants of diabetic mothers.

Auditory brain stem responses potentials were recorded from 71 newborns within the first 2 weeks after birth; conceptional age ranged from 37 to 41 weeks. Thirty-nine newborns were infants of diabetic mothers (IDMs) (17 White A, 22 White B-D) and 32 healthy term newborns served as control group. IDMs with additional high risk for cochlear or brain stem integrity were excluded. Birthweight for gestational age was significantly higher for IDMs. No differences in auditory brain stem responses wave latencies or amplitudes were observed between healthy infants of the control group and IDMs.

Birth Weight↗
PubMed1992

[Reducing the incidence and morbidity of very low birth weight premature infants after maternal transport to a perinatal center].

An improvement in the mortality and morbidity of very low-birth-weight infants could be confirmed by the regionalisation of high-risk pregnancies. The immaturity of premature newborn limits the therapeutic success. Our aim is therefore on the one hand, to make an early diagnosis of patients at risk of threatened premature delivery, and secondly, to provide intensive therapy for women already showing symptoms of premature delivery, to achieve the best possible prognosis. A reduction in the number of very low birth-weight infants and their mortality and morbidity rate appears to be possible if the pregnant women can be placed in a perinatal centre in good time; if the pregnancy can be prolonged and fetal lung maturation can be induced by betamethasone; if the delivery can be managed carefully, avoiding hypoxaemia, shock situations, and trauma; in certain cases this would mean performing a caesarean section by isthmo-cervical longitudinal incision; if primary neonatal care is performed by an experienced neonatologist. With the standard of neonatology as it is today, a considerable increase in the survival rates of very low birth-weight infants can hardly be expected. Nevertheless, to cut down their numbers is the biggest potential for the future reduction of the infant mortality rate.

Adolescent↗
PubMed1992

Narcotic and nicotine effects on the neonatal auditory system.

To evaluate narcotic and nicotine effects on the neonatal auditory system, brain stem auditory evoked responses were recorded in 15 infants prenatally exposed to both narcotics and nicotine (median gestational age 38.4 weeks, median birth weight 2820 g), in 15 nicotine exposed infants (gestational age 40.0 weeks, birth weight 3000 g) and in 24 healthy term infants (gestational age 40.1 weeks, birth weight 3310 g) who served as controls. Whereas nicotine-exposed and control infants were similar in all brain stem auditory evoked response measurements, narcotic/nicotine infants had bilaterally increased wave V latencies (left: p = 0.005; right: p = 0.04) and I-V intervals (left: p = 0.02; right: p = 0.01) when compared to controls. Our findings suggest that prenatal narcotic but not nicotine exposure negatively affects maturation or integrity of the neonatal auditory brain stem tract and that neither narcotic nor nicotine exposure is associated with hearing loss in the neonate.

Brain Stem↗