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Biomedical subjects

Mikael Norman

Publications and source records attributed to Mikael Norman.

18 recordsLinked to original sources

Generation of NO by probiotic bacteria in the gastrointestinal tract.

Probiotic bacteria elicit a number of beneficial effects in the gut but the mechanisms for these health promoting effects are not entirely understood. Recent in vitro data suggest that lactobacilli can utilise nitrate and nitrite to generate nitric oxide, a gas with immunomodulating and antibacterial properties. Here we further characterised intestinal NO generation by bacteria. In rats, dietary supplementation with lactobacilli and nitrate resulted in a 3-8 fold NO increase in the small intestine and caecum, but not in colon. Caecal NO levels correlated to nitrite concentration in luminal contents. In neonates, colonic NO levels correlated to the nitrite content of breast milk and faeces. Lactobacilli and bifidobacteria isolated from the stools of two neonates, generated NO from nitrite in vitro, whereas S. aureus and E. coli rapidly consumed NO. We here show that commensal bacteria can be a significant source of NO in the gut in addition to the mucosal NO production. Intestinal NO generation can be stimulated by dietary supplementation with substrate and lactobacilli. The generation of NO by some probiotic bacteria can be counteracted by rapid NO consumption by other strains. Future studies will clarify the biological role of the bacteria-derived intestinal NO in health and disease.

Animals↗

Detecting heart defects in newborn infants--innocent murmurs mixed with silent dangers.

UNLABELLED: Detection of severe heart defects without unnecessary delay is a primary task for providers of infant care. Screening is challenged by the fact that a normal physical examination after birth does not exclude severe defects. Shorter hospital stay for newborn infants and a reduced number of examinations may further hamper a successful mission. Reassuringly, most critical heart defects are reported to be identified early. CONCLUSION: Increased awareness of the limitations of screening and continued monitoring of detection rates, as well as studies on how they can be improved, are warranted.

Early Diagnosis↗

Shorter hospital stay for moderately preterm infants.

AIM: To determine length of hospital stay (LOS) for moderately preterm infants during the last 20 years, and to identify factors affecting the number of bed-days. METHODS: Review of LOS for all infants delivered between 30 to 34 gestational weeks during 1983, 1988, 1993, 1998 and 2002. EXCLUSION CRITERIA: life-threatening abnormalities, chromosomal anomalies and death during hospitalization. RESULTS: 564 included infants accounted for 20% of admissions and 48% of bed-days in the neonatal unit. Between 1983 and 2002, maternal age and use of nasal continuous positive airway pressure increased, use of antibiotics and mechanical ventilation decreased, whereas distributions for gestational age, birthweight, gender, smallness for gestational age, low Apgar score or incidence of respiratory distress syndrome did not change. For healthy inborn singletons discharged home, LOS decreased from 1983 (28+/-11 d, mean+/-SD values) to 2002 (14+/-7 d, p<0.05). Infants born more immature had longer LOS, but postconceptional age at discharge did not differ between age groups. CONCLUSION: LOS for moderately preterm infants has decreased as a result of individualized neonatal care and organization of homecare support. Shorter LOS is of benefit to the family, prevents overcrowding in the NICU and has important economic implications.

Apgar Score↗

Preterm birth in Sweden: what are the average lengths of hospital stay and the associated inpatient costs?

AIM: To provide estimates of the first-year length of stay and inpatient costs of Swedish infants admitted for neonatal care by week of gestation and by birthweight; and to provide estimates of the length of stay and inpatient costs of delivering mothers during the ante- and postpartum period by week of gestation and birthweight of the infant. METHODS: Population-based registry study covering all live singleton deliveries in Sweden between 1998 and 2001 (n=336 136). First-year hospitalizations of infants admitted for neonatal care 0-6 d after birth (n=24 583) were tracked, as were hospitalizations of mothers for whom the date of admission lay+/-1 mo from the date of delivery. Monetary values were assigned to each hospitalization using the Nord-DRG classification system. RESULTS: On average, preterm infants (GA < 37 wk) had first-year lengths of stay roughly four times as long as full-term infants admitted for neonatal care (30 d vs 8 d, p<0.0001). The average first-year length of stay of the extremely immature infants (GA 22-25 wk) was more than six times as long that of infants born at 34-36 wk (108 d vs 17 d, p<0.0001). Mothers delivering preterm had an average length of stay slightly more than twice as long (p<0.0001) as that of mothers of full-term infants during the ante- and postpartum period. CONCLUSION: The estimated lengths of stay and costs may serve as reference values for a Swedish setting.

Hospitalization↗

Risk of high blood pressure among young men increases with the degree of immaturity at birth.

BACKGROUND: Survivors of preterm birth constitute a new generation of young adults, but little is known about their long-term health. We investigated the association between gestational age (GA) and risk of high blood pressure (HBP) in young Swedish men and whether GA modified the risk of HBP; ie, whether HBP was related to being born small for gestational age (SGA). METHODS AND RESULTS: This population-based cohort study included 329 495 Swedish men born in 1973 to 1981 who were conscripted for military service in 1993 to 2001. Multivariate linear- and logistic-regression analyses were performed. Main outcome measures were systolic and diastolic BPs at conscription. Linear-regression analyses showed that systolic BP increased with decreasing GA (regression coefficient -0.31 mm Hg/wk, P<0.001). Systolic and diastolic BPs both increased with decreasing birth weight for GA, but the association with systolic BP was most evident (regression coefficient -0.67 mm Hg per SD score in birth weight for GA, P<0.001). Compared with men born at term (GA, 37 to 41 weeks), the adjusted odd ratios (95% confidence intervals [CIs]) for high systolic BP (> or =140 mm Hg) were as follows: moderately preterm (33 to 36 weeks), 1.25 (1.19 to 1.30); very preterm (29 to 32 weeks), 1.48 (1.30 to 1.68); and extremely preterm (24 to 28 weeks), 1.93 (1.34 to 2.76). Being SGA was associated only with an increased risk of high systolic BP among men born at 33 weeks or later. The risk estimates for high diastolic BP (> or =90 mm Hg) increased with decreasing GA, but the risk reached significance only among men born moderately preterm. CONCLUSIONS: Preterm birth, a common pregnancy complication, is a risk factor for HBP in young men. The risk of high systolic BP associated with birth weight for GA is modified by GA, suggesting that perinatal contributions to BP elevation later in life may be induced by different biological pathways.

Adult↗

Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls.

Preterm birth might induce permanent changes in vascular structure and function as well as in blood pressure. To elucidate this hypothesis and underlying mechanisms in girls born before term, the authors correlated neonatal data, including estradiol levels, with vascular function and structure and with blood pressure after puberty. In a case-control study design, 34 girls born before term and 32 gender- and age-matched control infants born at term were included. Pulse wave analysis was used to determine aortic pressure profiles and overall arterial compliance. Stiffness of the carotid artery and abdominal aorta was measured with ultrasonography. Pulse wave velocity in the forearm was measured with photoplethysmography. A laser Doppler technique was used to determine skin perfusion before and after transdermal delivery of acetylcholine, an endothelium-dependent vasodilator. It was found that preterm girls had significantly higher brachial and aortic blood pressure, a narrower but less stiff abdominal aorta, and lower peripheral skin blood flow than did control infants. Augmentation index, carotid stiffness, pulse wave velocity, endothelium-dependent vasodilatation, and heart rate were similar in the two groups. In the preterm group, blood pressure and vascular functions showed no association with intrauterine growth retardation or neonatal estradiol levels. In conclusion, preterm girls have higher blood pressure and an increased resistance in the vascular tree after puberty. These findings may have implications for future cardiovascular risk in the growing adult population surviving preterm birth.

Adolescent↗

A pilot study of inhaled nitric oxide in preterm infants treated with nasal continuous positive airway pressure for respiratory distress syndrome.

OBJECTIVE: To explore the acute effects of inhaled nitric oxide (iNO) on oxygenation, respiratory rate, and CO2 levels in spontaneously breathing preterm infants treated with nasal continuous positive airway pressure (nCPAP) for moderate respiratory distress syndrome (RDS). DESIGN AND SETTING: Randomized, prospective, double-blind, cross-over study in the neonatal intensive care units of a university hospital. PATIENTS: 15 infants treated for RDS, with a median gestational age of 32 weeks (27-36), birth weight 1940 g (1100-4125), and postnatal age at the beginning of study 23 h (3-91). nCPAP pressure was kept constant at 4.3 cmH2O (3.4-5.1). INTERVENTIONS: We examined effects on gas exchange and vital signs during a 30-min exposure to 10 ppm iNO or placebo gas (nitrogen). RESULTS: Before administering test gases the baseline arterial to alveolar oxygen tension ratio (aAPO2) was 0.19+/-0.06. aAPO2 remained unchanged during placebo but increased to 0.22+/-0.05 (+20%) during iNO exposure. Respiratory rate and arterial carbon dioxide tension remained unchanged, as did heart rate, blood pressure, and methemoglobin. Follow-up at 30 days of age showed no deaths, delayed morbidity, or need for supplemental oxygen. CONCLUSIONS: Adding 10 ppm nitric oxide to nasal CPAP treatment in preterm infants suffering from RDS results in a moderate but statistically significant improvement in oxygenation, with no effect on respiratory drive or systemic circulatory parameters.

Administration, Inhalation↗

Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses.

OBJECTIVE: To investigate whether intrauterine growth retardation (IUGR) and preterm delivery in a poor population of South Asia was associated with altered maternal and fetal levels of folate, vitamin B12, and homocysteine. SUBJECTS AND METHODS: Hundred and twenty-eight pregnant women from a low socio-economic strata in the city of Lahore, Pakistan were followed with ultrasound of fetal growth from the 12th week of pregnancy. Blood samples were drawn from the woman and the cord at delivery. Serum was analyzed by a chemiluminescent immunoassay for folate and vitamin B12 and by fluorescence polarization immunoassay for total homocysteine (tHcy). RESULTS: Fourty-six infants showed IUGR. In term, but not preterm, deliveries with IUGR, maternal and cord blood folate levels were half of those in deliveries of normal birth weight infants (P=0.004 and P=0.005). The risk of IUGR was reduced among women with folate levels in the highest quartile (OR 0.31, 95% CI 0.10--0.84). There was no association between vitamin B12 and IUGR. Total homocysteine levels were higher in women delivering IUGR infants (P=0.02). There was an inverse correlation between cord blood folate and tHcy levels (r=-0.26, P=0.006). We also found increased risks for hypertensive illness (OR 3.5, 95% CI 1.4--8.6) and premature delivery (OR 2.5, 95% CI 1.1--6.2) in women in the highest quartile of tHcy. CONCLUSIONS: The occurrence of IUGR increased with low maternal and cord concentrations of folate and high maternal levels of tHcy. Further studies on the effects of vitamin B supplementation through pregnancy are warranted.

Adult↗

Blood glucose testing at alternate sites in newborn infants.

AIM: To compare a method of testing at alternate skin sites (AST) with that of the usual heel-stick approach (SM) for determining blood glucose levels in newborn infants. Our other aims were to compare these methods as regards their accuracy, the pain caused by the procedures, the times taken to obtain a result and the possible delay in accurate test results using AST during rapid changes in blood glucose. METHODS: One hundred and eighty-six preterm and term infants were enrolled. The blood glucose levels were determined by a standard bedside method (SM, HemoCue) and AST (Freestyle), which permitted blood samples to be taken from the arm or leg. RESULTS: The levels of blood glucose ranged between 0.6 and 8.6 mmol/l. We found a significant correlation between SM and AST (r = 0.90, p < 0.001). The coefficient of variation was similar, pain was significantly less (median pain score 3.5 vs 7.5, p < 0.01) and the time taken to obtain a result significantly shorter (mean 35 vs 111 s, p < 0.01) with AST than with SM. No significant differences were found between these methods during rapid changes in the blood glucose levels. CONCLUSION: AST, a relatively simple and painless method of determining blood glucose levels in newborn infants, is acceptably accurate and causes minimal blood loss.

Age Factors↗

[Successful breast feeding after neonatal intensive care].

We have performed a follow-up study of breastfeeding in 1,696 infants (734 preterm) admitted for neonatal intensive care. Six months after discharge from hospital, 80% of term infants were breastfeeding, exclusively or in part. This does not differ from national statistics for all babies born in Sweden. The corresponding breastfeeding frequency among very preterm infants (gestational age < 30 w) was 47%. As maturity evolves and morbidity becomes subsidiary, breastfeeding can be successfully established in most preterm and previously sick neonates. This information provide reassuring support for their mothers.

Breast Feeding↗

Palivizumab prophylaxis and hospitalization for respiratory syncytial virus disease in the Stockholm infant population, 1999 through 2002.

BACKGROUND: There are few independent, population-based reports that estimate the risk of hospitalization of respiratory syncytial virus (RSV)-infected infants before and during the palivizumab era. We present figures from the greater Stockholm area during the three seasons after the introduction of palivizumab and relate them to data based on 1400 hospitalizations for RSV disease in the same population area during 1987 through 1998. METHODS: The number of births, neonatal complications and palivizumab prescriptions was obtained. We retrieved information about all infant hospitalizations for confirmed RSV infections with risk factors and complications. Chronic lung disease (CLD) in preterm infants was defined as oxygen dependency beyond 36 weeks of postconceptional age. RESULTS: Eight hundred eighteen infants (1.3% of the population) were hospitalized for confirmed RSV infection. The hospitalization rates were 3.7% (24 of 642) among preterm infants with gestational age <33 weeks without CLD and 7.2% (14 of 195) in those with CLD. Palivizumab had been given to 235 infants, usually those with CLD and in need of continuous oxygen or steroid treatment or the <6 month-old infants with extremely preterm birth (gestational age <26 weeks). The risk of hospitalization for RSV disease was low, but this was the case also before the introduction of palivizumab. CONCLUSIONS: In countries with a low baseline risk of hospitalization for RSV infection, the benefit of palivizumab might not justify the cost of its widespread use. We advocate defining more rigorous prescription criteria.

Antibodies, Monoclonal↗

Non-invasive assessment of endothelial function - relation between vasodilatory responses in skin microcirculation and brachial artery.

OBJECTIVE: To compare different non-invasive methods for determination of human endothelial function in peripheral circulation. DESIGN: Observational, cross-sectional study in 39 healthy subjects (21 females, age 17-56 years). SETTING: Vascular research laboratory at university hospital. METHODS: Laser Doppler (LD) flowmetry was used to compare skin microvascular perfusion changes during postocclusive reactive hyperaemia with those induced by iontophoretic administration of acetylcholine (ACh), an endothelial-dependent vasodilator. LD measurements were compared with ultrasonographic measurements of postocclusive flow-mediated dilatation (FMD) in the brachial artery (n = 21). RESULTS: Local ACh induced a larger and more sustained skin perfusion increase than reactive hyperaemia after 4 min of regional arterial occlusion (P<0.001). A significant correlation was found between the magnitude of ACh-induced vasodilatation and peak reactive hyperaemia, both in absolute (r = 0.62, P<0.001) and relative terms (r = 0.58, P<0.001). A correlation was also found between brachial artery FMD and the magnitude of ACh-induced skin perfusion increase (r = 0.43, P<0.05) but not between FMD and reactive hyperaemia. CONCLUSION: Endothelial function, an early marker of cardiovascular risk, can be non-invasively assessed and graded by LD and FMD-measurements and despite inherent differences, both methods do correlate.

Adolescent↗

Preterm delivery, level of care, and infant death in sweden: a population-based study.

OBJECTIVE: To elucidate the role of level of care in combination with other perinatal risk factors for infant death in very preterm deliveries. DESIGN: Population-based cohort study. SETTING: Sweden, 1992-1998. SUBJECTS: Singleton infants (2285) born at 24 to 31 completed weeks of gestation to primiparous women. MAIN OUTCOME MEASURE: Infant mortality. RESULTS: The rate of infant mortality increased from 5% among infants born at 31 weeks' gestation to 56% among infants born at 24 weeks' gestation. Compared with infants born at university hospitals, the unadjusted odds ratio (OR) of infant death was 0.70 (95% confidence interval [CI]: 0.54-0.90) among infants delivered at general hospitals. However, after adjustment, the OR of infant death shifted to 1.33 (95% CI: 0.88-2.02) for preterm births at general hospitals. This shift was primarily due to different gestational age distributions in regional and general hospitals. Among infants born at 24 to 27 weeks' gestation, infant mortality rates were 23% (87 deaths) in university hospitals and 32% (73 deaths) in general hospitals, giving an adjusted OR of 2.00 for general versus university hospitals (95% CI: 1.15-3.49). The risk of death at 24 to 27 weeks' gestation in general hospitals was increased specifically in pregnancies with placental complications. CONCLUSION: Taking obstetric complications into account, there is an excess mortality risk among extremely preterm infants born at general hospitals.

Delivery, Obstetric↗

Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial.

OBJECTIVE: Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement. METHODS: Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation. RESULTS: In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group. CONCLUSIONS: The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe.

Algorithms↗

Preterm birth attenuates association between low birth weight and endothelial dysfunction.

BACKGROUND: Low birth weight predisposes to later coronary disease. To further elucidate the mechanisms behind this association and their timing, vascular endothelial function-a key factor in early pathophysiology of atherosclerosis-was studied in 54 infants born either before the third trimester or at term. METHODS AND RESULTS: All subjects were studied at 3 months of postnatal age. A laser-Doppler technique was used to measure skin perfusion before and after transdermal iontophoresis of acetylcholine (ACh; an endothelium-dependent vasodilator). In infants born at term (n=19; birth weight range: 2230 to 4205 g), maximum perfusion after ACh was 109+/-8 perfusion units (PU, mean+/-SEM) in normal-birth weight controls compared with 56+/-13 PU among those who had been small for gestational age at birth (P<0.01). In infants born preterm (n=35; birth weight range, 722 to 1868 g), ACh induced similar perfusion responses among subjects appropriate for gestational age (113+/-16 PU) and in those small for gestational age at birth (109+/-19 PU). CONCLUSIONS: Impairment in human endothelial function associated with low birth weight occurs or emerges late in pregnancy. Very preterm birth attenuates this association. Different gene-environment interactions in the third trimester may contribute to this finding.

Acetylcholine↗

[Tympanic thermometers are of great value for health check ups of newborn infants].

In a study of 81 healthy, newborn infants (60 term, postnatal age 2-18 h) tympanic and axillary measurements were compared with rectal temperatures. Mean (95% confidence interval) rectal temperature was 36.9 degrees C (36.8-37.0 degrees C), min-max range: 35.9-37.8 degrees C. Mean tympanic temperature was 36.8 degrees C (36.7-36.9 degrees C) and axillary 36.5 degrees C (36.3-36.6 degrees C). Rectal temperature < 36.5 degrees C (< -1SD, N = 10): tympanic sensitivity 80% (44-97%) and axillary 70% (35-93%), tympanic specificity 87% (77-94%) and axillary 60% (48-72%). Rectal temperature > 37.4 degrees C (> +1SD, N = 7): tympanic sensitivity 86% (42-100%) and axillary 0% (0-41%), tympanic specificity 95% (97-99%) and axillary 99% (93-100%). Tympanic measurements give valuable information in checking for normal body temperature in newborn infants.

Axilla↗