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Background To decrease contamination of needleless catheter hubs, caps or port protectors impregnated with isopropanol (IPA) have been developed and shown to be superior to other disinfection methods. The safety of the caps has been questioned, as they can be associated with alcohol leakage across the hub membrane. Objectives We evaluated the use of IPA caps and the scrub-the-hub method from the safety standpoint of possible alcohol leakage across the hub membrane. Methods Circuits imitating an intravenous line were constructed. Circuits with an IPA cap were flushed with sodium chloride after the hub had been exposed to the cap for 1 hour, 24 hours, and 7 days. At the end of each period the fluid was collected and amounts of IPA in it were measured, using gas chromatography. Scrub circuits without IPA caps were also tested and ethanol from these was measured using the same method. Results In this in vitro study, IPA was detected in all samples from cap circuits, and ethanol was detected from all scrub circuits. Leakage increased over time in IPA circuits. After 24 hours and 7 days of exposure, the first injection resulted in higher amounts of IPA; thereafter, the levels decreased. The amounts of ethanol measured from the scrub circuits were low. Conclusions IPA caps can cause leakage of alcohol across the hub membrane. Leakage increased over time, and a 30 sec drying time was not sufficient to solve the problem. Scrub-the-hub seems safe to use with regard to alcohol leakage.

A balance has evolved over deep time between the various immune systems of the "triad" that is linked together for a short period: the pregnant woman, the fetus, and the placenta. This balance is a ...

Aim: To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs var ...

The aim of the study was to investigate whether there is any association between cerebral palsy (CP) and celiac disease (CD) in children.Ninety children between 18 months and 18 years of age (median 9 years) with CP were included. Antibodies (IgA and IgG) against gliadin (AGA), endomysium (EMA), and tissue transglutaminase (tTG) were measured. Children with elevated levels of these antibodies were offered a small-bowel biopsy.Thirty-nine children showed an elevated level of 1 or more of the tested antibodies (43%). None had raised EMA antibodies. Presence of tetraplegia or dyskinesia was associated with increased antibody levels (P=0.045), as was a more severe functional type of CP (P=0.008). Children with elevated antibodies had a lower body weight (P=0.049), height (P=0.041), and body mass index (BMI) (P=0.014). Small-bowel biopsies were performed in 27 out of 39 children; 1 had CD and 2 had intraepithelial lymphocytosis.A large number of children with CP had elevated AGA and/or anti-tTG. Because these elevations were associated with lower weight, height, and BMI, it seemed of interest to speculate on how these findings correlated to CP and CD. However, we found no correlation between CP and CD.

To evaluate a real-time PCR assay for the diagnosis of neonatal bacteraemia.Two hundred ninety-five plasma samples from 288 newborns with suspected neonatal sepsis were collected prospectively for the purpose of polymerase chain reaction (PCR)-based bacterial detection. A real-time PCR targeting the bacterial gene for 16S-rRNA gene combined with four specific probes designed to detect Gram-negative bacteria, Staphylococcus aureus and coagulase-negative staphylococci (CoNS) was developed. All samples positive in the universal PCR were further sequenced for bacterial identification.When applied to a material from 50 patients with positive blood culture and 245 patients with negative blood culture, the universal PCR showed a sensitivity of 42% (28-57), a specificity of 95% (92-97), a positive predictive value of 64% (45-80), and a negative predictive value of 89% (84-92) (95% confidence intervals in brackets).A new real-time PCR technique was for the first time applied to a well-defined prospectively and consecutively enrolled material of newborns with suspected sepsis, combining the benefits of real-time PCR with specific probes and sequencing. The method managed to detect bacteraemia with high specificity even though the sensitivity was low. Factors causing the low sensitivity are identified and further strategies to develop the method are described.

Aim: To investigate vascular function in children with a neonatal history of generalised inflammation indicated by premature prolonged rupture of membranes (PPROM) and bronchopulmonary dysplasia (BPD). Methods: Children born at ≤ 30 weeks 1994–2000 were investigated at a present age of 6–12 years. Twenty-eight children participated and were divided into two groups with regard to BPD/no BPD (n = 15/13) and PPROM/no PPROM (n = 10/18). Vascular endothelial function was assessed by acetylcholine (ACh)-induced skin vasodilatation. Results: Maximum ACh-induced skin perfusion was statistically significantly lower in the PPROM group compared with the non-PPROM group (p = 0.045) after adjustment for confounders. We found no association between BPD and maximum ACh-induced skin perfusion (p = 0.404), after adjustment for confounders. Conclusion: A neonatal history of prolonged premature rupture of membranes was associated with later impairment of vascular endothelial function in childhood. This association was not observed with BPD. Some forms of perinatal inflammation may be associated with later cardiovascular function.

AIM: To assess the ability of galvanic skin response (GSR) to differentiate between tactile and painful stimulation in newborn infants, and to compare this with the ability of the premature infant ...

Aim: To investigate whether professional training and/or clinical experience affect the ability of caregiver to assess clinical signs of pre-emptive morphine analgesia. Methods: In the Neurological Outcomes & Pre-emptive Analgesia In Neonates trial preterm infants undergoing mechanical ventilation were randomized to receive continuous infusion, either of morphine or placebo blinded. Staff from centres in Sweden (Stockholm and Orebro) completed an assessment form. Results: A total of 360 assessment forms were collected from 52 neonates. In 59% of the cases, caregivers correctly identified patients group. Comparable proportion of answers were correct between physicians, nurses and assistant nurses (63, 60 and 54%, respectively, p = 0.60). Staff with Neonatal intensive care unit experience 5 years (p = 0.28). Staff's ability to correctly identify group assignment was reduced by amount of additional morphine (p < 0.01) and severity of illness (p = 0.01). Conclusions: Clinical medical staffs, including neonatologists, have great difficulties in assessing the presence and severity of pain. Further studies should focus on the methods for assessment of prolonged pain in preterm neonates, define the effects of adequate analgesia, and investigate the clinical factors that may alter neonatal responses to acute and prolonged pain.

Knowledge about long-term electrocardiographic changes after surgery for congenital heart disease is limited.Eleven patients with corrected tetralogy of Fallot (ToF) and 14 with corrected atrial septal defect (ASD) were followed up at 20 and 30 years after surgery.Approximately 50% of the ASD group developed prolonged QRS duration. In the ToF group, 7 increased QRS duration by more than 20 milliseconds. Nearly all had right bundle-branch block, and 30% of them also had bifascicular block. Two in the ASD group developed first grade atrioventricular block. Five ASD and 6 ToF had prolonged corrected QT duration in the late postoperative phase.Even after primarily good results of surgery in congenital heart disease, unknown late effects may occur not only in complex lesions such as ToF but also after ASD correction. Regular medical checkups are important after surgical correction in congenital heart disease.

To describe the parent's judgement of their own stress and the child's behaviour at 18 months after pre-term birth and if there are any correlations between these assessments, the morbidity in the neonatal period, the gestational age at birth and the occurrence of twin/triplet births.Twenty-one mothers and 19 fathers of pre-term infants answered two questionnaires, The Swedish Parenthood Stress Questionnaire (SPSQ) and The Toddler Behaviour Questionnaire (TBQ).Mothers scored somewhat higher than fathers concerning parental stress. Parents with twins/triplets and of children born in gestational week 25-30 felt more stress, though the differences were not statistically significant. High-risk diagnoses did not correlate to any of the dimensions. The parents judged the behaviour of the children similar except that parents of children born in gestational week 25-30 scored significantly higher for intensity/activity (p = 0.002). The correlation between parental stress and judgement of their children's behaviour did not show any significant association except for the dimension regularity in TBQ (p = 0.016).The mothers' and fathers' assessments of their own stress and of the children's behaviour were similar. Parents of very pre-term children felt more stress and judged the children somewhat delayed in their social behaviours, probably due to their low gestational age.

Aim: To determine whether sepsis caused by coagulase-negative staphylococci (CoNS) is a risk factor for developing bronchopulmonary dysplasia (BPD) in premature newborns. Methods: All newborns born at ±30 wk of gestation at Orebro University Hospital during 1994–2001 with clinical sepsis caused by CoNS (group A, n= 22) or by other bacteria (group B, n= 17) were included and compared with premature newborns without sepsis (group C, n= 53). Clinical sepsis was defined as a positive blood culture (monoculture) plus clinical symptoms and laboratory findings. BPD was defined as treatment with oxygen >21% for at least 28 d. Results: The incidence of BPD differed between the three groups, as follows: CoNS sepsis (A) 64%, other sepsis (B) 41% and control (C) 24%. The difference between the control group and the sepsis groups was highly significant (p= 0.006). In a univariate model the crude estimates of relative risk (RR) for occurrence of BPD increased with presence of sepsis and particularly with presence of sepsis with CoNS (A: RR 2.6, 95% CI 1.5–4.6, p= 0.001; B: RR 1.7, CI 0.8–3.5, p= 0.17). When regression was performed with two additional predictive variables in multivariate models including sepsis, gestational age and mechanical ventilation (group A: RR 1.5, CI 1.1–2.0, p= 0.004; group B: RR 0.9, CI 0.6–1.4, p= 0.67), the estimates were lower. Conclusion: The relative risk for BPD is significantly increased in premature newborns with sepsis caused by CoNS compared with those with sepsis caused by other bacteria and compared with premature newborns with no sepsis.

This study was conducted to evaluate the accuracy and kinetics of interleukin 8 (IL-8) as a test for early-onset bacterial infections (EOBI) in neonates and to examine whether IL-8 would allow unnecessary antibiotic therapy to be reduced. First, IL-8 was measured 378 times on admission, along with C-reactive protein (CRP), immature to total neutrophil ratio (IT ratio) and blood cultures, in full-term and preterm neonates with suspected EOBI. Combined culture-proven and clinical EOBI were detected on admission by the combination of IL-8 > 70 pg ml -1 and/or CRP > 10 mg l -1 with 92% sensitivity and 74% specificity. An increased IL-8 was found in 62% of the infected infants, while CRP was still normal. In a second study period, IL-8 was determined prospectively in 331 infants who presented clinical signs of EOBI or had a birth history of amniotic infection. Antibiotic therapy was restricted to those infants with suspected infection who also had an increased IL-8 and/or CRP (n = 158). Another 39 infants received antibiotics on the basis of clinical signs despite negative IL-8 and CRP. Of 150 non-infected infants in whom IT ratio, IL-8 and CRP were available, treatment would have been indicated for 93 infants based on IT ratio and/or CRP (n = 77) or clinical signs (n = 16), hut was only initiated in 55 infants based on IL-8 and/or CRP (n = 28) or clinical signs (n = 27), an apparent reduction in unnecessary antibiotic therapy of 40%. Conclusion: The combination of IL-8 and CRP is a reliable test for the diagnosis of EOBI and may be helpful in enabling antibiotic therapy to be reduced in newborn infants.

The purpose of this study was to investigate if early samples of interleukin-6 (IL-6) could distinguish early bacterial sepsis from respiratory diseases in the newborn. IL-6 and C-reactive protein (CRP) were measured at onset of symptoms in newborns evaluated for sepsis during the first week of life. Five groups of children were investigated: proven sepsis, clinical sepsis, respiratory distress syndrome (RDS), transient tachypnoea of the newborn (TTN) and controls. IL-6 was also analysed at the time when CRP was at its maximum level. The results showed that initial IL-6 distinguished proven and clinical sepsis from TTN, but not from RDS. Initial CRP was of no value for diagnosis. Our conclusion is that early IL-6 makes it possible to avoid antibiotics in children with TTN and contributes to the diagnosis of sepsis faster than CRP.

AIM: Palivizumab (Synagis) was registered in Sweden in 1999 for prophylaxis against respiratory syncytial virus (RSV) in premature infants. The high costs and the limited knowledge of the efficacy of this substance have led to debate about how and when it should be used. National guidelines for the use of palivizumab in Sweden were constructed in the year 2000. The aim of this study was to evaluate the guidelines. METHODS: A nation-wide prospective study was conducted during the two RSV seasons of the years 2000-2002. The paediatric departments in Sweden reported the use of palivizumab, the indication for its use, and the number of infants born preterm before 36 wk of gestation and less than 2 y old who were admitted to hospital for RSV infection. RESULTS: During the two seasons, 218 (3.8%) children who were born before 36 wk of gestation, and 97 (5.4%) who were born before 33 wk, were hospitalized because of RSV infection. Five children were treated with mechanical ventilation. No death caused by RSV was reported. A total of 390 children were treated with palivizumab, and 16 (4.1%) of those who received prophylactic treatment were admitted to hospital with RSV infection. CONCLUSION: We consider the comparatively restrictive Swedish recommendations to be safe and recommend that palivizumab should also be used very restrictively in the future. In our opinion, palivizumab in preterm children could be recommended only for those with chronic lung disease younger than 1 y of age, and with active treatment for their disease.

Introduction One of the targets of national health programs is to prevent unintended pregnancies, especially among teenagers. It is well established that these often lead to abortion. Preventive programs aimed at decreasing abortion rates should identify target groups at risk for unintended pregnancies. Purpose This study was conducted to determine whether young mothers under 20 years of age constitute a group at risk for new unintended pregnancies. Methods A retrospective cohort study comprising teenagers giving birth to their first child from 1996 to 2000 was performed at Orebro University Hospital, Sweden. Data were collected from antenatal and medical records with particular regard to compliance with the postpartum visit and to whether a contraceptive method was prescribed. Information concerning repeat pregnancies during the 12 months after delivery was obtained. Results A total of 250 deliveries were recorded; 70% of the mothers attended the postpartum visit, and 71% received contraceptive prescriptions. At the 12-month follow-up, 56 (25%) had a new pregnancy, and of those, 20 (36%) had a legal abortion, making the abortion rate fivefold higher than expected in this age group. Conclusion This study shows that teenagers giving birth constitute a high-risk group for future unintended pregnancies and legal abortion.

This study evaluated sepsis as a risk factor for neonatal morbidities and investigated the association between specific pathogens and neonatal morbidities.This was a nationwide Swedish prospective cohort study, consisting of the 497 extremely premature children, who were born before 27 weeks of gestation between 2004 and 2007 and survived their first year of life. Neonatal sepsis was evaluated as a risk factor for neonatal morbidity using multiple logistic linear regression analyses.We found that 326 (66%) of the infants had at least one sepsis episode and coagulase-negative staphylococci was the most common pathogen. Definite sepsis, with an odds ratio (OR) of 1.6, was associated with severe bronchopulmonary dysplasia, but not clinical sepsis (OR 1.1). Definite sepsis was also associated with a prolonged hospital stay (OR 1.6). Sepsis was not significantly associated with a higher risk of retinopathy of prematurity or intraventricular haemorrhage.Extremely preterm infants face a great risk of acquiring neonatal sepsis, with coagulase-negative staphylococci being the most common pathogen in this population. Definite sepsis seemed to be a risk factor for severe bronchopulmonary dysplasia and prolonged hospital stay, but the associations were weaker than in previous studies.

Objective. It has been demonstrated clearly that sweet-tasting solutions given before a painful intervention can reduce pain among newborns. There is no fully accepted explanation for this effect, but activation of endogenous opioids has been suggested as a possible mechanism. The aim of this study was to obtain deeper knowledge of the underlying mechanism by investigating whether administration of an opioid antagonist would reduce the effect of orally administered glucose at heel stick among term newborns. Design. A randomized, placebo-controlled, double-blind trial with a validated, neonatal, pain-rating scale. Participants. The trial included 30 term newborns undergoing heel stick, who were assigned randomly to 1 of 2 groups, ie, group I, with naloxone hydrochloride (opioid antagonist) 0.01 mg/kg administered intravenously before oral administration of 1 mL of 30% glucose, or group II, with a corresponding amount of placebo (saline solution) administered intravenously before oral administration of glucose. Outcome Measures. Pain-related behavior during blood sampling was measured with the Premature Infants Pain Profile. Crying time and heart rate were also recorded. Results. The 2 groups did not differ significantly in Premature Infant Pain Profile scores during heel stick. The median crying time during the first 3 minutes was 14 seconds (range: 0–174 seconds) for the naloxone group and 105 seconds (range: 0–175 seconds) for the placebo group. There was no significant difference in heart rate between the 2 groups. Conclusion. Administration of an opioid antagonist did not decrease the analgesic effect of orally administered glucose given before blood sampling.

Newborn infants, especially those born preterm, are immunologically immature and prone to invasive infections. As a result of the increasing survival of very preterm (VPT < 31 weeks gestational age) newborns, nosocomial septicaemia has become a major concern the neonatal intensive care, and coagulase-negative staphylococci (CoNS) are nowadays the most frequently isolated pathogens in neonatal blood cultures. Further insight into host-bacterial interactions is required for the development of preventive strategies against CoNS septicaemia in VPT newborns.Aim of the study: To investigate host-bacterial interactions in neonatal CoNS septicaemia with special regard to the neutrophil and endothelial response and to bacterial virulence factors.Methods and results: Neonatal blood isolates of CoNS collected at Orebro University Hospital, Orebro, Sweden during the years 1983-1997 were characterised clinically and according to species and to phenotypic and genotypic patterns. Biochemial fingerprinting was found useful as a screening tool for selection of phenotypically related strains, but for further discrimination within a phenotypic cluster, genetic fingerprinting by pulsed field gel electrophoresis (PFGE) was required.The isolates of S. epidermidis collected during the later part of the study period (1990-1997, n = 50) were further investigated. A hypervirulent clone of bacteria was identified, representing 7 of the 12 sepsis isolates in that cohort. These 12 isolates of S. epidermidis induced significantly higher endothelial release of neutrophil chemoattractants from human umbilical vein endothelial cell (HUVEC) cultures than did the isolates regarded as skin contaminants (n = 38). There were no differences between the sepsis and contaminant groups in the prevalence of genes for biofilm production, methicillin resistance or fibrinogen-binding protein.The neutrophil oxidative burst occuring after stimulation by different bacterial strains was investigated by a flow cytometric method applied to a whole blood model. The oxidative activity in unstimulated neutrophils was similar in term (n = 10) and preterm (n = 10) newborns. However, the term newborns showed a significantly higher capacity to up-regulate the oxidative burst after bacterial stimulation. Significant differences in oxidative responses to different bacterial strains were observed, but these differences could not be related exclusively to species or invasive capacity.A neutrophil granule protein, human neutrophil lipocalin (HNL), was evaluated as an early marker of neonatal septicaemia in newborns with clinical signs of infection. The serum level of HNL was significantly higher in the infected group of neonates (n = 25) than in the group with non-proven infection (n = 62). In healthy term controls the HNL level was similar at age 3 days to that at birth and close to the level reported in healthy adults.Conclusions: The increased up-regulation of endothelial inflammatory mediators induced by sepsis isolates of S. epidermidis represents an important step in the pathogenesis of neonatal CoNS septicaemia. HNL might be useful as a marker of neutrophil activity also in VPT newborns. The laboratory assays used in the present study can be further developed for future investigations of the pathogenesis and host-bacterial interactions in neonatal CoNS septicaemia.

Aims: The aims of this study were to compare the pain reducing effect of oral glucose with that of being breast-fed shortly before venipuncture in newborns, and also the pain score and crying time with parents' assessment. Design: Randomised, controlled trial. Subjects: 120 full term newborns undergoing venipuncture randomly assigned to on of four groups: I, Breast-fed and 1-ml placebo; II, Breast-fed and 1-ml 30% glucose; III, Fasting and 1-ml placebo; and IV, Fasting and 1-ml 30% glucose. Outcome measures: Pain during venipuncture was measured with the Premature Infant Pain Profile (PIPP). Crying time was recorded. The parents assessed their babies' pain on a Visual Analogue Scale (VAS). Results: The PIPP score was significantly lower in the infants receiving glucose, than in those not given glucose (p=0.004). There was no significant difference in PIPP score between the infants who were fed and the fasting infants. The PIPP score was lower in group II (median 7) than in group I (md 10). There was a similar difference between group IV (md 9) and group III (md 11). The median crying times during the first 3 min in groups I, II, III, and IV were 63, 18, 142 and 93 s, respectively. There was low agreement between the parents' assessment of pain and the PIPP score and crying time. Conclusion: Breast-feeding shortly before venipuncture has no major impact on the pain score but on crying time. The combination of oral glucose and breast-feeding shows the lowest pain score and significantly shorter duration of crying.

BACKGROUND: The birth of a preterm infant has a long-term impact on both parents. Mothers report more stress and poor adjustment compared with fathers. Influencing factors, such as family situation ...

Objective: The responsibility for treating children with asthma has gradually shifted from the medical health service to the family and parents, which may cause new psycho-social problems in the family. This study aimed at describing the psycho-social effects on families having a child with asthma, and at determining whether a relation exists between the medical severity of disease and psycho-social problems. Methods: The findings are based on a questionnaire with the following domains: economy, work, free time, health, environment, and family, as well as a health-related medical questionnaire. They are built on psycho-social problems and on medical records. Results: The frequency of psycho-social problems was high regarding single questions in the evaluated psycho-social domains. A relation was found between high drug consumption and severe psycho-social problems. However, no positive correlation was detected among visits at the hospital's emergency department, absence from school due to asthma or disturbed sleep, and psycho-social problems. On the contrary, a negative correlation was found between absence from school due to asthma and psycho-social problems. Conclusion: We conclude that for single questions in each psycho-social domain, the problem rate is high, but when taking into account the mean value of different psycho-social problems in each domain, the reported problem rate is fairly low. This method permits selection of the psycho-social domains with the most severe problems in each family. It can, therefore, be used to direct help from the medical service. We also found a relation between the medical severity of asthma and the extent of the psycho-social problems caused by the disease.

Our knowledge of pain in neonates has increased significantly during the last fifteen years.We now have an improved understanding of the pain system and of the negative effects of untreated pain. Advances in neonatal care have increased the nwnber of preterm and severely ill infants who are treated in neonatal intensive care units (NICU). These infants are subjected to a variety of painful procedures as part of their management. Sufficient pain relief is needed and for this, valid pain assessment is one prerequisite.The aim of this research was to improve the management of procedural pain and to examine the assessment of neonatal pain in clinical practice.In an earlier study, oral glucose was found to reduce pain during blood sampling. To further evaluate the pain-reducing effect of oral glucose and to compare this effect with different blood sampling techniques, a trial was performed. The pain score was lower and crying time shorter in the venipuncture group than in the heel stick group when no glucose was given. When glucose was administered, the pain score was lower in both glucose groups than in the groups not receiving glucose (paper I).In a randomized, controlled study, the effect of oral glucose was compared with that of a topical local anaesthetic, EMLA, during venipuncture. The pain scores were found to be lower in the glucose group and fewer infants were scored as having pain. Crying time was also shorter in the glucose group (paper II).To compare the pain-reducing effect of oral glucose with that of breast-feeding shortly before venipuncture, a new trial was performed. The pain score was significantly lower in the infants receiving glucose than in those not given glucose. There was no significant difference in pain score between the infants who were fed and the fasting infants (paper III).In a previous study we found an increase in heart rate in newboms when they received glucose as pain relief. We therefore investigated whether oral glucose in itself could cause an increase in heart rate in healthy infants. In a trial, infants were randomized to receive oral glucose or placebo without undergoing any painful procedure. The heart rate was significantly higher in the glucose than in the placebo group (paper IV).Activation of endogenous opioids is suggested as one possible mechanism underlying the pain-reducing effect of oral glucose. We therefore investigated whether administration of an opioid antagonist would reduce the effect of oral glucose at heel stick in full-term newboms. There were no significant differences in pain score or crying between the group receiving an opioid antagonist before oral glucose and the group receiving placebo before oral glucose during heel stick (paper V).To document whether pain is assessed in Swedish neonatal units and by what methods, a questionnaire was distributed to all neonatal wards in Sweden in 1993, and again in 1998. Only a small proportion of neonatal units in Sweden attempted to assess pain. There was a minor increase in the nwnber of wards that used a structured method for pain scoring. Docwnentation of pain is still inadequate and needs to be improved (paper VI). We compared parental assessment during blood sampling with measurement of the pain score with a multidimensional tool and crying. There was low agreement between these variables during the procedure (paper III).In conclusion, we found that oral glucose reduces signs of pain from both heel stick and venipuncture blood sampling. Oral glucose reduces pain better than does EMLA cream and better than if the infant is breast-fed shortly before the procedure. Oral glucose increases the heart rate in infants and the pain-reducing effect of oral glucose in newboms was not diminished by injection of an opioid antagonist. Parental assessment of an infant's pain cannot replace measurement by pain scores. The pain assessment at neonatal units in Sweden needs to be improved.

Coagulase-negative staphylococci (CNS) are the leading cause of late-onset sepsis in newborns (>72 h of age). Our aim was to determine whether phenotypic and/or genotypic differences existed between blood isolates of CNS regarded as inducers of sepsis or as contaminants. Ninety-seven bloodisolates of CNS recovered from newborns at the neonatal intensive care unit, Orebro, Sweden in 1983-1997 were analysed. Twenty-nine of them (30%) were classified as sepsis isolates and 68 (70%) as contaminants. The most prevalent species was Staphylococcus epidermidis (n=59). Staphylococcus haemolyticus (n=16) was most often isolated from newborns with the lowest gestational age and birth weight. Biochemical typing using the Phene Plate system (PhP) and genotyping using pulsed-field gel electrophoresis (PFGE) showed that the S. epidermidis isolates regarded as inducers of sepsis (n=16) were more homogeneous than isolates considered contaminants (n=37). One main genotypic group, representing seven (44%) isolates, was identified among the sepsis isolates. Phenotypically the S. epidermidis sepsis isolates comprised three major clusters. In contrast, among the S. epidermidis contaminants, eight genotypic groups and two phenotypic clusters were identified. The dominating genotypic group among the sepsis isolates of S. epidermidis may represent strains with higher invasive capacity.

Despite an increase in the prevalence of asthma during the last few decades, the need for hospital treatment of children with asthma has become less. One reason for this is that children and their parents are now more involved in the treatment of the disease, and responsibility has been shifted from the medical care system to the family. This new responsibility may cause increased psycho-social tension within the family. We conducted a pilot study on three limited methods of intervention to find the best way to help families in this respect. All three methods (individual family meetings, family group meetings, and evaluation of the child's environment in school) reduced the psycho-social burden of having a child with asthma. This indicates that families should be supported by being given the opportunity to participate in meetings to discuss the disease or to have the environment in the child's school evaluated, in addition to receiving regular medical care.

The objectives of this study were to measure pain symptoms in healthy fullterm newborns undergoing routine blood sampling with different methods. The 120 study subjects were randomly allocated to one of four groups with 30 babies in each, namely venepuncture or heel stick, with or without oral glucose administration. Pain was assessed from the duration of crying within the first 3 min, the Premature Infant Pain Profile (PIPP) and changes in heart rate. When the babies received 1 ml 30% glucose prior to skin puncture there was no significant difference between the heel stick and venepuncture group either in mean crying time (12.9 and 11.6 s, respectively) or in PIPP score (3.9 and 3.3). When no glucose was given crying time was 57.3 s in the heel stick group and 26.8 s in the venepuncture group (P = 0.0041) and the mean PIPP scores were 8.4 and 6.0, respectively (P = 0.0458). This study suggests that if oral glucose is given prior to skin puncture the choice of blood sampling method has no impact on the pain symptoms.

There is evidence that newborn babies feel pain even at the lowest gestational ages when they can survive. Because sweet solutions such as sucrose, given orally, may relieve pain in neonates, we decided to compare the effects of two concentrations of glucose (normally used for intravenous infusions) and of breast milk in a randomized controlled trial in 120 babies requiring heel-prick tests. Glucose solutions and breast milk are readily available in the neonatal department. No other treatment was given. Our results strongly suggest that 1 ml of a 30% glucose solution given orally alleviates mild pain significantly and can be used for this purpose in newborns. Breast milk and 10% glucose did not have a similar effect.

Aim: Staphylococci are a major contribution for neonatal sepsis, which is the main risk factor for bronchopulmonary dysplasia. This study investigated the expression of proinflammatory mediators in endothelial and respiratory cells from newborns exposed to staphylococci. Methods: Human vascular endothelial cells and small airway epithelial cells were incubated with neonatal blood isolates of Staphylococcus epidermidis (n = 14) and Staphylococcus aureus (n = 14). The extracellular release of IL-8, IL-10, sICAM-1, ICAM-1 mRNA and the expression of membrane bound ICAM-1 were assessed by ELISA, RT-PCR and immunofluorescence microscopy. Results: Staphylococcus epidermidis induced higher levels of IL-8 (mean 38.5 ng/mL) and ICAM-1 mRNA (mean ratio 1.037) in the small airway epithelial cells than S. aureus (IL-8 mean 22.2 ng/mL, p < 0.01 and ICAM-1 mRNA mean ratio 0.715, p < 0.01). In the endothelial cells, ICAM-1 remained more integrated in the cell membranes after exposure to S. epidermidis compared with S. aureus, which induced disintegration and release of soluble ICAM-1 into the supernatants. Conclusion: Staphylococcus epidermidis induced a higher chemoattractive response than S. aureus. A persistent transmigration of granulocytes into the lung tissue in neonatal S. epidermidis sepsis might contribute to the development of bronchopulmonary dysplasia.

UNLABELLED Prevention, treatment and assessment of neonatal pain have been of major clinical and scientific interest the last decades. Non-pharmacological interventions such as sweet oral solutions are successful in pain relief. Whether breast milk, with its lactose content of 7%, has any effect on the prevention of pain has been debated. CONCLUSION Randomized studies of breast milk in prevention and treatment of neonatal pain are needed.

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the ‘Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)’ study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400–999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants.

A balance has evolved over deep time between the various immune systems of the "triad" that is linked together for a short period: the pregnant woman, the fetus, and the placenta. This balance is affected by, and helps to determine, the immune responses to maternal infectious agents that may be transmitted to the fetus/infant transplacentally, intrapartum, or via breast milk. This review identifies newer evolutionary concepts and processes related particularly to the human placenta, innate and adaptive immune systems involved in tolerance, and in responses to sexually transmitted infectious (STI) agents that may be pathogenic to the fetus/infant at different gestational periods and in the first year of life. An evolutionary-developmental (EVO-DEVO) perspective has been applied to the complexities within, and among, the different actors and their beneficial or deleterious outcomes. Such a phylogenetic and ontogenic approach has helped to stimulate several basic questions and suggested possible explanations and novel practical interventions.

Background: The standard diagnostic test (blood culture) for suspected neonatal sepsis has limitations in sensitivity and specificity, and 16S polymerase chain reaction (PCR) has been suggested as a new diagnostic tool for neonatal sepsis. Objectives: To develop and evaluate a new real-time PCR method for detection of bacterial DNA in blood samples collected from infants with suspected neonatal sepsis. Methods: Immediately after blood culture, a study sample of 0.5–1.0 ml whole blood was collected and used for a novel 16S real-time PCR assay. All positive samples were sequenced. Detailed case studies were performed in all cases with conflicting results, to verify if PCR could detect pathogens in culture negative sepsis. Results: 368 samples from 317 infants were included. When compared with blood culture, the assay yielded a sensitivity of 79%, a specificity of 90%, a positive predictive value of 59%, and a negative predictive value of 96%. Seven of the 31 samples with a positive PCR result and a negative blood culture had definite or suspected bacterial sepsis. In five samples, PCR (but not blood culture) could detect a pathogen that was present in a blood culture collected more than 24 h prior to the PCR sample. Conclusions: This study presents an evaluation of a new real-time PCR technique that can detect culture-positive sepsis, and suggests that PCR has the potential to detect bacteria in culture-negative samples even after the initiation of intravenous antibiotics.

A model using human umbilical vein endothelial cells was developed to study the adhesion of group B streptococci. Ten clinical isolates of serotypes Ia, Ib and III, including six blood isolates from neonates with early-onset disease, were studied. Isogenic variants with different ability to express capsule substance were also included. Clinical isolates of serotype III adhered significantly better than other serotypes. Strains with high ability to adhere to endothelial cells also had high ability to bind to plastic. Isogenic variants of serotype III with low amounts of capsule substance adhered significantly better to cells than variants expressing high amounts of capsule substance. These results show that the higher adherence of serotype III strains may be a virulence factor and contribute to the finding that this serotype dominates in invasive group B streptococcal disease.

Summary Breast milk contains pro- and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (CBMCs) and intestinal epithelial cells (IECs, cell line HT-29) to microbial challenge. Ninety-five women were included: 30 from Mali in West Africa, 32 Swedish immigrants and 33 native Swedish women. CBMCs or IECs were stimulated in vitro with breast milk, alone or in combination with lipopolysaccharide (LPS) or peptidoglycan (PGN). Breast milk in general abrogated the LPS-induced down-regulation of surface CD14 and Toll-like receptor (TLR)-4 expression on CB monocytes, while inhibiting the PGN-induced TLR-2 up-regulation. However, breast milk from immigrant women together with LPS induced a lower CBMC release of interleukin (IL)-6 (P = 0·034) and CXCL-8/IL-8 (P = 0·037) compared with breast milk from Swedish women, while breast milk from Swedish women and Mali women tended to increase the response. The same pattern of CXCL-8/IL-8 release could be seen after stimulation of IECs (HT-29). The lower CBMC and IEC (HT-29) responses to microbial compounds by breast milk from immigrant women could be explained by the fact that breast milk from the immigrant group showed a divergent pro- and anti-inflammatory content for CXCL-8/IL-8, transforming growth factor-β1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses.

To identify which clinical signs at presentation are most predictive of sepsis subsequently confirmed by blood culture and to investigate whether the predictive power of the clinical signs varies by gestational age.Among 401 newborn infants28 days of age with suspected sepsis, nine signs of sepsis and C-reactive protein (CRP) values were prospectively recorded. Logistic regression assessed the association of these signs and laboratory values with a subsequently confirmed diagnosis of sepsis by positive blood culture. The analysis was stratified by gestational age with mutual simultaneous adjustment for the signs and sex.Five of the nine clinical signs (feeding intolerance, distended abdomen, blood pressure, bradycardia and apnoea), along with CRP were statistically significantly associated with a positive blood culture. After simultaneous adjustment for all of the signs, apnoea, hypotension and CRP were independently predictive of positive blood culture. When the material was stratified by gestational age, differences in the association with positive blood culture were found for bradycardia, tachypnea and irritability/seizures.In this selected population of infants with suspected sepsis, apnoea and hypotension are independently predictive of a confirmed diagnosis, while bradycardia is more predictive among preterm infants and tachypnea among term infants.

International audience; Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified ( = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2-3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.

Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

The purpose of the present investigation was to use an intra-individual experimental-control study design to explore if application of Emdogain prior to re-plantation after a dry extra-alveolar period of 60 min would promote a favorable healing of the periodontal ligament cells. Ten patients, for whom already decisions had been taken to extract two maxillary premolars because of crowding, participated in the study. The teeth were extracted and endodontic treatment was performed extra orally. The experimental tooth and its alveolar socket were covered with Emdogain prior to replantation. The contra lateral tooth served as a control and was replanted without any prior treatment. The teeth were stabilized with a retainer for 3-7 days and the patients were followed up every third week. After 13 weeks, the teeth were finally extracted and prepared for histological examination. Radiographs were taken before the study period, at day 29 and prior to the final extraction. The results were in favor of Emdogain, but the overall difference between the Emdogain-treated tooth and its control was rather small, and it seemed questionable if the registered differences could be of any obvious practical clinical importance. Histologically, all the teeth showed some degree of pathology after such a long dry extra-oral time and the outcome seemed to be more correlated to the individual than to the treatment. Given more favorable conditions regarding storage medium and/or extra-oral time, Emdogain might still be of value for an uncomplicated healing after replantation.

To assess the ability of galvanic skin response (GSR) to differentiate between tactile and painful stimulation in newborn infants, and to compare this with the ability of the premature infant pain profile (PIPP).Thirty-two healthy full-term infants undergoing routine blood sampling were recruited. In a randomized order they were subjected to tactile and painful stimulation. The three GSR variables conductance baseline level, number of waves per second and mean amplitude of the waves were recorded together with the behavioural and physiological variables of PIPP.The GSR variables number of waves and amplitude of the waves increased more during painful stimulation than during tactile stimulation, as did also the PIPP score. Receiver operating characteristic curves analysis revealed no significant differences between the studied methods.GSR can differentiate painful from tactile stimulation, but more research is needed to achieve a clinically useful application.

In nine children with severe cerebral palsy (CP), feeding difficulties and poor development of weight and height, laboratory markers for metabolic and enteral dysfunction were studied. CONCLUSION: Four of the nine patients with CP had increased levels of antigliadin antibodies AGA (IgA), a finding which calls for further studies concerning the possible connection between increased celiac markers and CP.

OBJECTIVE. To assess neonatologists' attitudes and practices regarding treatment of extremely preterm infants in the delivery room, particularly in response to parental wishes.STUDY DESIGN. Cross-sectional survey of all neonatologists in Sweden registered with the Swedish Pediatric Society.RESULTS. The response rate was 71% (88 of 124 neonatologists). At 24[1/7] to 24[6/7] weeks of gestation, 68% of neonatologists considered treatment clearly beneficial; at 25[1/7] to 25[6/7] weeks of gestation, 93% considered it clearly beneficial. When respondents consider treatment clearly beneficial, 97% reported that they would resuscitate in the delivery room despite parental requests to withhold treatment. At or below 23[0/7] weeks of gestation, 94% of neonatologists considered treatment futile. Nineteen percent reported that they would provide what they consider futile treatment at parental request. When respondents consider treatment to be of uncertain benefit, 99% reported that they would resuscitate when parents request it, 99% reported that they would resuscitate when parents are unsure, and 25% reported that they would follow parental requests to withhold treatment.CONCLUSION. Although neonatologists' attitudes and practices varied, respondents to our survey in general envisioned little parental role in delivery room decision-making for extremely preterm infants.

To study the subjective opinions about what is important in care at neonatal units and child health centres (CHCs) for premature newborns, and to compare these opinions with the care actually given.21 mothers, 20 fathers and 15 nurses at the neonatal unit, and 21 mothers, 14 fathers and 18 nurses at CHCs.A questionnaire on quality of Care from the Patient's Perspective was used. It contained three dimensions: identity-oriented approach, medical-technical competence and socio-cultural atmosphere. Each dimension was evaluated in terms of subjective importance and perceived reality of given care.In general, subjective importance was rated higher than perceived reality both for neonatal care and care at CHCs for the dimensions identity-oriented approach and medical-technical competence. However, higher ratings were given to neonatal care compared to CHCs for medical-technical competence. High-risk diagnoses and very low gestational age in the newborn did not affect the answers. Mothers rated medical-technical competence higher than nurses for neonatal care. Mothers and nurses rated identity-oriented approach higher than fathers for CHCs.Although both neonatal care and care at CHCs were highly rated, improvements can be made to fulfil the expectations of parents and nurses. Neonatal units seem to be more efficient in taking care of the special needs of these newborns compared to CHCs. The need for an optimal identity-oriented approach, medical-technical competence and socio-cultural atmosphere could strengthen the possibilities of parents to be confident in their parental role.

The limit of viability is intensely debated. Newborns below 500 g birthweight are often small for gestational age with an increased risk of short- and long-term mortality and morbidity. The level of given neonatal care must be individualized. A long-term follow-up for newborns with extremely low birthweight is urgently needed.

The neutrophil oxidative burst is a product of the regulated assembly of the multicomponent oxidase enzyme. Our aim was to compare the oxidative burst in term (n = 10) and preterm newborns