Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring.

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-ß1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses.

Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia.

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 (n = 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.

Seeing through the blind! Ability of hospital staff to differentiate morphine from placebo, in neonates at a placebo controlled trial.

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 <1 year identified 63%, as compared to 65% for working 1-5 year, and 55% that has been working >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.

Is there a connection between severe cerebral palsy and increased gluten sensitivity?

UNLABELLED: 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.

Appropriate prophylaxis with restrictive palivizumab regimen in preterm children in Sweden.

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.

Analgesic effect of expressed breast milk in procedural pain in neonates.

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.

Human neutrophil lipocalin: normal levels and use as a marker for invasive infection in the newborn.

AIM: To evaluate human neutrophil lipocalin (HNL) as a marker of neonatal invasive infection and determine the normal serum levels of HNL in newborns. METHODS: HNL is released from neutrophil granulocytes and is regarded as a specific marker of neutrophil activity. In 81 newborns < or = 28 d of age with signs of infection on a total of 87 occasions, HNL and C-reactive protein (CRP) were measured at inclusion and on the three following days. As controls, term healthy newborns were recruited at birth (cord blood, n = 45) and at ages 3-5 d (n = 46). Serum HNL was measured by a radioimmunoassay. RESULTS: 25/87 episodes were classified as infection and 62 as non-proven infection. HNLmax was significantly higher in the infected group (mean 587.6 microg/l) than in the non-proven infected group (mean 217.7 microg/, p < 0.001). HNL peaked at inclusion, 1 d earlier than CRP. In the healthy controls. HNL was the same at 3-5 d of age as at birth (mean 82.4-81.7 microg/l) and similar to normal adult levels. CONCLUSIONS: The release of HNL is not increased in healthy newborns at birth, but neonatal neutrophils rapidly release HNL upon microbial stimulation in vivo. HNL might be useful as an early marker of neonatal infection.

Coagulase-negative staphylococcal sepsis as a predictor of bronchopulmonary dysplasia.

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 < or = 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.

Can severity-of-illness indices for neonatal intensive care predict outcome at 4 years of age?

AIM: To test four neonatal severity-of-illness indices (CRIB, NTISS, SNAP, SNAP-PE) for their ability to predict short- and long-term outcome in very low-birthweight infants receiving neonatal intensive care. METHODS: Data on 240 newborns with birthweights below 1500 g from two Swedish neonatal units were collected. The predictive values of the indices for an adverse outcome in the neonatal period and at 4 y of age were compared with those of gestational age and birthweight. RESULTS: An early adverse outcome (in-hospital death, severe haemorrhagic-ischaemic brain lesion, retinopathy, chronic lung disease) was better predicted with CRIB (area under ROC curve (Az) = 0.87) and SNAP-PE (Az = 0.86), while SNAP-PE was best for predicting late problems (deviations in growth and psychomotor development, neurosensory impairment, difficulties in concentration, and impairment in vision, and hearing) (Az = 0.63). All indices predicted the early outcome better than the outcome at the 4-y follow-up. Severity-of-illness indices can be used as instruments to follow and improve the level of neonatal intensive care, but unfortunately seem to be of little value in long-term follow-up. CONCLUSION: CRIB and SNAP-PE indices are better in predicting hospital mortality than birthweight. None of the systems can predict adverse outcome at 4 y of age.

Utilization of healthcare by very-low-birthweight infants during their first year of life.

New knowledge in perinatal medicine has resulted in increased survival of very-low-birthweight (VLBW) infants. After leaving hospital, the child is seen at regular medical check-ups, but there is often a persistent worry about the child which affects the family as a whole. This can lead to an increased utilization of healthcare. Our objective was therefore to describe the utilization of healthcare by VLBW infants during their first year of life and its relation to high-risk diagnoses in the neonatal period. The study group comprised 36 infants born at gestational ages of < or = 31 wk and with a birthweight of < or = 1500 g, and was compared with a control group of 36 full-term infants. Utilization of healthcare by the VLBW infants was higher than that by the control group in paediatric and ophthalmic outpatient clinics. The total number of contacts with healthcare was on average 38.7 versus 17.4. High-risk diagnoses in the neonatal period did not correlate with utilization of care, except for visits to the paediatric outpatient clinic, especially planned visits. Further studies focusing on how to support these families after leaving hospital are therefore needed.

Monitoring of early postnatal glucose homeostasis and cerebral function in newborn infants of diabetic mothers. A pilot study.

The aims of this pilot study were to evaluate a new technique in the monitoring of postnatal glucose homeostasis (microdialysis) and also to study possible associations between early postnatal hypoglycaemia and influences on cerebral function monitoring (CFM) in 12 newborn infants of diabetic mothers. In order to study the postnatal glucose homeostasis, frequent dialysate samples were obtained from a subcutaneous microdialysis catheter for measurements of glucose. In addition, we also received samples of dialysate lactate and glycerol. Dialysate glucose concentrations were correlated to capillary blood glucose levels, measured by a glucose oxidase method. The cerebral function monitor was applied postnatally and a registration was obtained continuously. Capillary blood glucose decreased initially, and seven newborns received intravenous glucose infusions due to glucose concentrations less than 2.2 mmol/l. Dialysate glucose concentrations were, on average, 0.4 mmol/l higher than corresponding concentrations in capillary blood. The correlation coefficient between the two measurements was 0.63 and the coefficient of variation was 19.2%. Dialysate lactate and glycerol levels increased significantly, with peak values 3-4 h postnatally. No significant overall influence of hypoglycaemia was detectable in the CFM tracing. We conclude that a relatively poor correlation was observed between glucose measurements in capillary samples and microdialysis. However, using the microdialysis technique saw indication of marked lipolysis and increased lactate production, which may be of importance for cerebral postnatal adaptation. The mild postnatal hypoglycaemia in infants of diabetic mothers does not seem to give visually detectable influences on CFM.

Quality of life 20 and 30 years after surgery in patients operated on for tetralogy of Fallot and for atrial septal defect.

Follow-up studies on patients operated on for congenital heart defects have shown good anatomical results and long-term survival. To date, there have been few studies on such patients with regard to long-term psychosocial outcome and quality of life. In this study, two cohorts of patients operated on before the age of 15 years, one for tetralogy of Fallot (TOF) and the other for atrial septal defect (ASD), were investigated 20 and 30 years after operation regarding quality of life. The combined cohort had a higher educational level than average. There was no connection between quality of life and physical health as judged from the New York Heart Association classification. The TOF group rated their quality of life higher than the ASD group, but both groups had lower figures at the 30-year than at the 20-year follow-up. Fewer patients in the TOF than in the ASD group considered that their lives were affected by the heart disease. It is concluded that the severity of the heart disease is not necessarily congruent with estimated quality of live and that mild heart defects, such as ASD, can have a considerable impact on later life quality. Surprisingly few TOF patients were affected negatively, a finding which might reflect development of a specific coping strategy in these patients during childhood.

[Cochrane report: sucrose reduces pain in newborns, optimal doses however not known]. / Cochrane-rapport: sackaros minskar smärta hos nyfödda, optimala doser dock okända.

Management of pain in newborns is less than optimal. We know for certain that newborns, even if born extreme premature, can feel pain. The assessment of pain is difficult and should include both physiological and behavioural parameters. The Cochrane Collaborative presents a review considering the efficacy of sucrose as analgesia in newborns undergoing painful procedures. The review shows that sucrose is efficient for procedural pain reduction even for premature newborns. The optimal doses are however not known and further studies must focus on efficacy and safety.

Intervention models on psycho-social health in families with an asthmatic child.

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 psychosocial 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.

Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome.

Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO2) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO2 when entering the study. There were no significant differences between the groups in a/A PO2 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice.

Contribution of interleukin-6 in distinguishing between mild respiratory disease and neonatal sepsis in the newborn infant.

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.

Oral glucose and venepuncture reduce blood sampling pain in newborns.

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.