Britt Nakstad

Improved Cognitive Development Among Preterm Infants Attributable to Early Supplementation of Human Milk With Docosahexaenoic Acid and Arachidonic Acid

OBJECTIVE. The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants. The primary end point was cognitive development at 6 months of age. METHODS. The study was a randomized, double-blind, placebo-controlled study among 141 infants with birth weights of <1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital (on average, 9 weeks). Cognitive development was evaluated at 6 months of age by using the Ages and Stages Questionnaire and event-related potentials, a measure of brain correlates related to recognition memory. RESULTS. There was no difference in adverse events or growth between the 2 groups. At the 6-month follow-up evaluation, the intervention group performed better on the problem-solving subscore, compared with the control group (53.4 vs 49.5 points). There was also a nonsignificant higher total score (221 vs 215 points). The event-related potential data revealed that infants in the intervention group had significantly lower responses after the standard image, compared with the control group (8.6 vs 13.2). There was no difference in responses to novel images. CONCLUSIONS. Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months.

Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study

Objective The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of ethnicity using the World Health Organization (WHO) and modified IADPSG criteria. Methods This was a population-based cohort study of 823 (74% of eligible) healthy pregnant women, of whom 59% were from ethnic minorities. Universal screening was performed at 28±2 weeks of gestation with the 75 g oral glucose tolerance test (OGTT). Venous plasma glucose (PG) was measured on site. GDM was diagnosed as per the definition of WHO criteria as fasting PG (FPG) ≥7.0 or 2-h PG ≥7.8 mmol/l; and as per the modified IADPSG criteria as FPG ≥5.1 or 2-h PG ≥8.5 mmol/l. Results OGTT was performed in 759 women. Crude GDM prevalence was 13.0% with WHO (Western Europeans 11%, ethnic minorities 15%, P=0.14) and 31.5% with modified IADPSG criteria (Western Europeans 24%, ethnic minorities 37%, P< 0.001). Using the WHO criteria, ethnic minority origin was an independent predictor (South Asians, odds ratio (OR) 2.24 (95% confidence interval (CI) 1.26–3.97); Middle Easterners, OR 2.13 (1.12–4.08)) after adjustments for age, parity, and prepregnant body mass index (BMI). This increased OR was unapparent after further adjustments for body height (proxy for early life socioeconomic status), education and family history of diabetes. Using the modified IADPSG criteria, prepregnant BMI (1.09 (1.05–1.13)) and ethnic minority origin (South Asians, 2.54 (1.56–4.13)) were independent predictors, while education, body height and family history had little impact. Conclusion GDM prevalence was overall 2.4-times higher with the modified IADPSG criteria compared with the WHO criteria. The new criteria identified many subjects with a relatively mild increase in FPG, strongly associated with South Asian origin and prepregnant overweight.

Incidence and characteristics of arthritis in Norwegian children: a population-based study.

OBJECTIVE. The purpose of this work was to assess the annual incidence of arthritis in children and describe early disease and patient characteristics, microbiologic features, and immunogenetic factors in children with different subgroups of childhood arthritis. PATIENTS AND METHODS. A population-based multicenter study was performed in southeastern Norway between June 1, 2004, and May 31, 2005. The total population of children under 16 years of age was 255303. Physicians were asked to refer their patients with suspected arthritis to the local department of pediatrics or rheumatology. The children were assessed on the basis of clinical, radiologic, and laboratory examinations at inclusion and followed up at 6 weeks, 6 months, and thereafter as long as clinically indicated. A chart review was performed to identify patients with arthritis who had not been included prospectively. RESULTS. The total annual incidence of arthritis was 71 per 100000 children. Transient arthritis, juvenile idiopathic arthritis, postinfectious arthritis, and infectious arthritis were found in 43, 14, 9, and 5 of 100000 children, respectively. The incidence was higher in children under the age of 8 years than in older children (107 vs 34 per 100000). Arthritis occurred more frequently in boys than in girls before the age of 8 years but not thereafter. The median age of onset was lower in children with infectious arthritis than in those with other types of arthritis. Monarthritis was less frequent in patients with juvenile idiopathic arthritis than in the other subgroups (64% vs 83%–100%). Ten percent of the patients had poststreptococcal reactive arthritis, and only 1 had enteropathic arthritis. Autoantibodies and the presence of HLA-B27 were associated with juvenile idiopathic arthritis. CONCLUSIONS. The annual incidence of childhood arthritis was 71 per 100000 children. We found several factors that may help in differentiating between subgroups of arthritis.

Comparison of broad range 16S rDNA PCR and conventional blood culture for diagnosis of sepsis in the newborn: a case control study

BackgroundEarly onset bacterial sepsis is a feared complication of the newborn. A large proportion of infants admitted to the Neonatal Intensive Care Unit (NICU) for suspected sepsis receive treatment with potent systemic antibiotics while a diagnostic workup is in progress. The gold standard for detecting bacterial sepsis is blood culture. However, as pathogens in blood cultures are only detected in approximately 25% of patients, the sensitivity of blood culture is suspected to be low. Therefore, the diagnosis of sepsis is often based on the development of clinical signs, in combination with laboratory tests such as a rise in C – reactive protein (CRP). Molecular assays for the detection of bacterial DNA in the blood represent possible new diagnostic tools for early identification of a bacterial cause.MethodsA broad range 16S rDNA polymerase chain reaction (PCR) without preincubation was compared to conventional diagnostic work up for clinical sepsis, including BACTEC blood culture, for early determination of bacterial sepsis in the newborn. In addition, the relationship between known risk factors, clinical signs, and laboratory parameters considered in clinical sepsis in the newborn were explored.ResultsForty-eight infants with suspected sepsis were included in this study. Thirty-one patients were diagnosed with sepsis, only 6 of these had a positive blood culture. 16S rDNA PCR analysis of blinded blood samples from the 48 infants revealed 10 samples positive for the presence of bacterial DNA. PCR failed to be positive in 2 samples from blood culture positive infants, and was positive in 1 sample where a diagnosis of a non-septic condition was established. Compared to blood culture the diagnosis of bacterial proven sepsis by PCR revealed a 66.7% sensitivity, 87.5% specificity, 95.4% positive and 75% negative predictive value. PCR combined with blood culture revealed bacteria in 35.1% of the patients diagnosed with sepsis. Irritability and feeding difficulties were the clinical signs most often observed in sepsis. CRP increased in the presence of bacterial infection.ConclusionThere is a need for PCR as a method to quickly point out the infants with sepsis. However, uncertainty about a bacterial cause of sepsis was not reduced by the PCR result, reflecting that methodological improvements are required in order for DNA detection to replace or supplement traditional blood culture in diagnosis of bacterial sepsis.

Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study

BackgroundOsteomyelitis can be difficult to diagnose and there has previously not been a prospective approach to identify all children in a defined geographic area. The aim of this study was to assess the annual incidence of osteomyelitis in children, describe the patient and disease characteristics in those with acute (< 14 days disease duration) and subacute osteomyelitis (≥ 14 days disease duration), and differentiate osteomyelitis patients from those with other acute onset musculoskeletal features.MethodsIn a population-based Norwegian study physicians were asked to refer all children with suspected osteomyelitis. Children with osteomyelitis received follow-up at six weeks, six months and thereafter as long as clinically needed.ResultsThe total annual incidence rate of osteomyelitis was 13 per 100 000 (acute osteomyelitis 8 and subacute osteomyelitis 5 per 100 000). The incidence was higher in patients under the age of 3 than in older children (OR 2.9, 95%: CI 2.3–3.7). The incidence of non-vertebral osteomyelitis was higher than the incidence of vertebral osteomyelitis (10 vs. 3 per 100 000; p = .002). Vertebral osteomyelitis was more frequent in girls than in boys (OR 7.0, 95%: CI 3.3–14.7). ESR ≥ 40 mm/hr had the highest positive predictive laboratory value to identify osteomyelitis patients at 26% and MRI had a positive predictive value of 85%. Long-bone infection was found in 16 (43%) patients. ESR, CRP, white blood cell count, neutrophils and platelet count were higher for patients with acute osteomyelitis than for patients with subacute osteomyelitis. Subacute findings on MRI and doctors delay were more common in subacute osteomyelitis than in acute osteomyelitis patients. Blood culture was positive in 26% of the acute osteomyelitis patients and was negative in all the subacute osteomyelitis patients.ConclusionThe annual incidence of osteomyelitis in Norway remains high. ESR values and MRI scan may help to identify osteomyelitis patients and differentiate acute and subacute osteomyelitis.

Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway

BackgroundAcute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints.Methods57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit.ResultsThe children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups.ConclusionChildren hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis.

Local activation of the coagulation and fibrinolysis systems in lung disease

Extravascular coagulation and fibrinolysis is an integral part of inflammatory reactions. Disordered expression of procoagulant and profibrinolytic factors by mononuclear phagocytes of the lung (i.e. lung alveolar macrophages (LAM) and interstitial macrophages) may have important bearings on inflammatory lung tissue destruction and repair. Based on this hypothesis we have measured the presence of trigger molecules and activation products of the coagulation and fibrinolytic system in cell-free bronchoalveolar lavage fluid and in bronchoalveolar cells. Patient groups with chronic obstructive disease (COLD) (n = 76), idiopathic pulmonary fibrosis (IPF) (n = 29), sarcoidosis (n = 22), lung cancer (n = 36), pneumonia (n = 39), acquired immunodeficiency syndrome (AIDS) (n = 17) and a control group (n = 60) were studied by bronchoalveolar lavage (BAL). In all patient groups tissue thromboplastin (TPL) and fibrinopeptide A (FPA) were significantly increased compared to controls. Plasminogen activator (PA) activity was significantly lower in patients than in normals, and usually associated with high levels of antifibrinolytic activity. The level of PA inhibitor (PAI-2) was not significantly higher in any patient group compared to controls. The sensitivity of the method for fibrin degradation products (FDP) analysis was not high enough to detect FDP in BAL fluid of control individuals, whereas such products could be demonstrated in 25-53% of patients in various categories. We conclude that disordered expression of procoagulant and plasminogen activator activities in bronchoalveolar lavage fluid may reflect a milieu that favours accumulation of fibrin in inflammatory lung tissue and form the basis for the development of pulmonary fibrosis.

National guidelines for treatment of jaundice in the newborn

Jaundice is the most common reason for instituting treatment in otherwise healthy as well as sick newborn infants. Herein, we describe the process employed in Norway to forge agreement on a set of treatment guidelines that are now used across the country. The Norwegian Pediatric Association was a key resource in this process, which involved contacts with all paediatric departments in Norway.

Extended series of cardiac compressions during CPR in a swine model of perinatal asphyxia

BACKGROUND The rationale for a compression to ventilation ratio of 3:1 in neonates with primary hypoxic, hypercapnic cardiac arrest is to emphasize the importance of ventilation; however, there are no published studies testing this approach against alternative methods. An extended series of cardiac compressions offers the theoretical advantage of improving coronary perfusion pressures and hence, we aimed to explore the impact of compression cycles of two different durations. MATERIALS AND METHODS Newborn swine (n = 32, age 12-36 h, weight 2.0-2.7 kg) were progressively asphyxiated until asystole occurred. Animals were randomized to receive compressions:ventilations 3:1 (n=16) or 9:3 (n=16). Return of spontaneous circulation (ROSC) was defined as a heart rate ≥ 100 beats min⁻¹. RESULTS All animals except one in the 9:3 group achieved ROSC. One animal in the 3:1 group suffered bradycardia at baseline, and was excluded, leaving us with 15 animals in each group surviving to completion of protocol. Time to ROSC (median and interquartile range) was 150 s (115-180) vs. 148 s (116-195) for 3:1 and 9:3, respectively (P = 0.74). There were no differences in diastolic blood pressure during compression cycles or in markers of hypoxia and inflammation. The temporal changes in mean arterial blood pressure, heart rate, arterial blood gas parameters, and systemic and regional oxygen saturation were comparable between groups. CONCLUSION Neonatal pigs with asphyxia-induced cardiac arrest did not respond to a compression:ventilation ratio of 9:3 better than to 3:1. Future research should address if alternative compression:ventilation ratios offer advantages over the current gold standard of 3:1.

Putative regulatory T cells are impaired in cord blood from neonates with hereditary allergy risk

The hygiene hypothesis implies that the increasing prevalence of allergy in ‘westernized’ countries is explained by reduced bacterial exposure in early life, but the underlying mechanism remains elusive. We therefore wanted to study the effect of bacterial lipopolysaccharide (LPS) on the generation of regulatory T (TR) cells in neonates, and to analyze differences between neonates with allergy risk because of a family history of atopy (FH+) and controls without such hereditary risk (FH−). Cord blood mononuclear cells from the FH+ and FH− groups were stimulated with β‐lactoglobulin in the presence of LPS. T‐cell phenotypes suggestive of TR cells [CD25+, CD25high and integrin (CD103+)], and the intracellular proliferation antigen Ki‐67 were quantified by flow cytometry. Release of the immunosuppressive cytokine transforming growth factor β1 (TGF‐β1) from its inactive complex was determined by enzyme‐linked immunosorbent assay. The analyses revealed the generation of T‐cell phenotypes suggestive of TR cells including a CD25high T‐cell subset which was inversely related to T‐cell proliferation (r = −0.54, p < 0.05) and to activation‐induced release of TGF‐β1 (r = −0.80, p < 0.001). The CD25high T‐cell subset tended to be impaired in the FH+ group (% of CD3+ T cells: FH+, 5.1% vs. FH−, 12.6%), and notably, the FH+ group showed a significantly reduced capacity for generation of both CD25+ (FH+, 16.2% vs. FH−, 34.9%; p < 0.01) and T cells (FH+, 2.1% vs. FH−, 3.9%; p < 0.05). Our findings suggested that early‐life exposure to a dietary antigen in the presence of LPS might modulate the immune system by generating TR cells. This capacity was impaired in neonates with hereditary allergy risk, but clinical follow‐up will be required to determine a possible effect on allergy emergence.