Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low.

PURPOSE: Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. METHOD: Pregnant women with moderate untreated depression were recruited in 2016-2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. RESULTS: Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers', measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. CONCLUSION: Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference.

Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.

Investigations for neonatal seizures.

Seizures during the neonatal period are always medical emergencies. Apart from the need for rapid anticonvulsive treatment, the underlying condition is often not immediately obvious. In the search for the correct diagnosis, a thorough history, clinical examination, laboratory work-up, neurophysiological and neuroradiological investigations are all essential. A close collaboration between neonatologists, neuropaediatricians, laboratory specialists, neurophysiologists and radiologists facilitates the adequate care of the infant.

Investigating the European perspective of neonatal point-of-care echocardiography in the neonatal intensive care unit--a pilot study.

UNLABELLED: Point-of-care functional neonatal echocardiography (fnECHO) is increasingly used to assess haemodynamic status or patency of the ductus arteriosus (PDA). In Australasia, 90 % of neonatal intensive care units (NICUs) practice point-of-care fnECHO. The Australian Society of Ultrasound Medicine offers a training certificate for fnECHO. In Europe, the use and indications of fnECHO and the extent of point-of-care fnECHO training and accreditation are unknown. We aimed to assess utilisation and training of fnECHO in Europe. For this, we conducted an email survey of 45 randomly chosen tertiary NICUs in 17 European countries. The recall rate was 89 % (n = 40). Neonatologists with skills in fnECHO worked in 29 NICUs (74 %), but paediatric cardiologists would routinely perform most fnECHOs. Twenty-four-hour echocardiography service was available in 31 NICUs (78 %). Indications for fnECHO included assessment of haemodynamic volume status (53 %), presence or absence of pulmonary hypertension of the neonate (55 %), indication for and effect of volume replacement therapy (58 %), PDA assessment and monitoring of PDA treatment (80 %). Teaching of fnECHO was offered to trainees in 22 NICUs (55 %). Teaching of fnECHO was provided by paediatric cardiologists (55 %) or by neonatologists (45 %). Only six (15 %) national colleges accredited fnECHO teaching courses. CONCLUSION: fnECHO is widely practiced by neonatologists across Europe for a broad range of clinical questions. However, there is a lack of formal training and accreditation of fnECHO skills. This could be addressed by designing a dedicated European fnECHO training programme and by agreeing on a common European certificate of fnECHO.

The quality of the outdoor environment influences childrens health -- a cross-sectional study of preschools.

AIM: To test how the quality of the outdoor environment of child day care centres (DCCs) influences children's health. METHODS: The environment was assessed using the Outdoor Play Environmental Categories (OPEC) tool, time spent outdoors and physical activity as measured by pedometer. 172/253 (68%) of children aged 3.0-5.9 from nine DCCs participated in Southern Sweden. Health data collected were body mass index, waist circumference, saliva cortisol, length of night sleep during study, and symptoms and well-being which were scored (1-week diary - 121 parent responders). Also, parent-rated well-being and health of their child were scored (questionnaire, 132 parent responders). MANOVA, ANOVA and principal component analyses were performed to identify impacts of the outdoor environment on health. RESULTS: High-quality outdoor environment at DCCs is associated with several health aspects in children such as leaner body, longer night sleep, better well-being and higher mid-morning saliva cortisol levels. CONCLUSION: The quality of the outdoor environment at DCCs influenced the health and well-being of preschool children and should be given more attention among health care professionals and community planners.

The prognostic value of early aEEG in asphyxiated infants undergoing systemic hypothermia treatment.

BACKGROUND: Induced moderate hypothermia (HT) for 72 h has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full-term infants. A pathological amplitude integrated EEG background as early as 3-6 h after birth, has been shown to correlate to poor prognosis. AIM: The aim of this study was to investigate the correlation between amplitude integrated EEG during HT treatment and short-term outcome in asphyxiated full-term infants with moderate/severe hypoxic-ischaemic encephalopathy. METHODS: Between December 2006 and December 2007, 24 infants were treated with moderate HT (33.5 degrees C for 72 h) using a cooling mattress. Motor functions were assessed at 4 and 12 months of age. RESULTS: Of the total birth cohort of 28,837 infants, 26 infants fulfilled the criteria for HT treatment (0.9/1000) of whom 23 was treated with HT and all of these infants had available amplitude integrated EEG data. Normal 1-year outcome was found in 10/15 infants with severely abnormal burst-suppression pattern or worse at 6 h of age. Severe abnormalities were found to be significantly predictive for abnormal outcome after 36 h. CONCLUSION: Among asphyxiated infants treated with HT, only those who had aEEG abnormalities persisting at and beyond 24 h after birth showed poor neurological outcome at 1 year.

Approach to seizures in the neonatal period: a European perspective.

UNLABELLED: In the neonatal period, seizures rank among the most common neurological symptoms, often indicating an underlying serious neurological condition. It is remarkable that although new tools have been incorporated into the diagnosis of neonatal seizures, there is no consensus about the therapeutic approach among different doctors and institutions. Hence, although phenobarbital is still considered the initial drug of choice, the protocols reported in the literature show a great variability in the approach to treatment of refractory seizures. We used a questionnaire to gain information regarding the treatment of seizures in the neonatal period in different European institutions. CONCLUSION: We conclude that phenobarbital is still the initial drug of choice followed by benzodiazepines, except in preterm infants with a birth weight below 1800 g. In refractory seizures, the use of continuous lidocaine infusion is most common. Of note, clinical studies with newer drugs have been mostly performed in the United States but not in Europe.

Cranial ultrasound and MRI at term age in extremely preterm infants.

OBJECTIVES: Conventional MRI at term age has been reported to be superior to cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in a previous study cUS was performed during the first 6 weeks only and not in parallel to MRI at term age. Therefore, the aim of the present work was to study brain injuries in preterm infants performing concomitant cUS and MRI at full-term age. METHODS: In a population-based cohort of 72 extremely low gestational age infants paired cUS and conventional MRI were performed at term age. Abnormalities on MRI were graded according to a previously published scoring system. On cUS images the lateral ventricles, the corpus callosum, the interhemispheric fissure and the subarachnoidal spaces were measured and the presence of cysts, grey matter abnormalities and gyral folding were scored. RESULTS: Moderate or severe WM abnormalities were detected on MRI in 17% of infants and abnormalities of the grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%) none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and cUS. CONCLUSIONS: All severe WM abnormalities identified on MRI at term age were also detected by cUS at term, providing the examinations were performed on the same day. Infants with normal cUS at term age were found to have a normal MRI or only mild WM abnormalities on MRI at term age.

Outdoor environmental assessment of attention promoting settings for preschool children.

The restorative potential of green outdoor environments for children in preschool settings was investigated by measuring the attention of children playing in settings with different environmental features. Eleven preschools with outdoor environments typical for the Stockholm area were assessed using the outdoor play environment categories (OPEC) and the fraction of visible sky from play structures (sky view factor), and 198 children, aged 4.5-6.5 years, were rated by the staff for inattentive, hyperactive and impulsive behaviors with the ECADDES tool. Children playing in large and integrated outdoor areas containing large areas of trees, shrubbery and a hilly terrain showed less often behaviors of inattention (p<.05). The choice of tool for assessment of attention is discussed in relation to outdoor stay and play characteristics in Swedish preschool settings. The results indicate that the restorative potential of green outdoor environments applies also to preschool children and that environmental assessment tools as OPEC can be useful when to locate and develop health-promoting land adjacent to preschools.

Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome.

BACKGROUND: Both prophylactic and early surfactant replacement therapy reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS) compared with later selective surfactant administration. However, continued post-surfactant intubation and ventilation are risk factors for bronchopulmonary dysplasia (BPD). The purpose of this review was to compare outcomes between two strategies of surfactant administration in infants with RDS; prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation. OBJECTIVES: To compare two treatment strategies in preterm infants with or at risk for RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation vs. later selective surfactant administration, continued mechanical ventilation, and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (who receive surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (who receive prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2006), CINAHL (1982 to December Week 2, 2006), EMBASE (1980 - December 2006), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006), Pediatric Research (1990 - 2006), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation vs. selective surfactant administration continued mechanical ventilation, and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on the incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, duration of oxygen therapy, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Stratified analysis was performed according to inspired oxygen threshold for early intubation and surfactant administration in the treatment group: inspired oxygen within lower (FiO2< 0.45) or higher (FiO2 > 0.45) range at study entry. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. MAIN RESULTS: Six randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs and symptoms of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.67, 95% CI 0.57, 0.79], air leak syndromes [typical RR 0.52, 95% CI 0.28, 0.96] and BPD [typical RR 0.51, 95% CI 0.26, 0.99]. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.62, 95% CI 1.41, 1.86]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.57 doses per patient, 95% CI 0.44, 0.69]. In stratified analysis by FIO2 at study entry, a lower threshold for treatment (FIO2< 0.45) resulted in lower incidence of airleak [typical RR 0.46 and 95% CI 0.23, 0.93] and BPD [typical RR 0.43, 95% CI 0.20, 0.92]. A higher treatment threshold (FIO2 > 0.45) at study entry was associated with a higher incidence of patent ductus arteriosus requiring treatment [typical RR 2.15, 95% CI 1.09, 4.13]. AUTHORS' CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2< 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2< 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation.

Implementation of surfactant treatment during continuous positive airway pressure.

OBJECTIVE: To study the effects of implementing a method for surfactant administration by transient intubation, INSURE (i.e. INtubation SURfactant Extubation) during nasal continuous positive airway pressure (nCPAP) for moderately preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN: A descriptive, retrospective, bi-center study in Stockholm, Sweden, comparing mechanical ventilation (MV) rates, surfactant use, treatment response and outcome of all inborn infants with gestational age 27 to 34 weeks and RDS, (n=420), during the 5-year periods before and after the introduction of the INSURE-strategy at one of the centers (Karolinska Huddinge) in 1998. The other center (Karolinska Solna) continued conventional surfactant therapy in conjunction with MV throughout the study. RESULTS: Implementation of INSURE at Karolinska Huddinge reduced the number of infants requiring MV by 50% (P<0.01), resulted in earlier surfactant administration and increased overall surfactant use. INSURE-treatment improved oxygenation and the treatment response was sustained over time with only 17% of the infants requiring >1 dose of surfactant. At Karolinska Solna, the MV rates were unaltered between the first and second 5-year period. CONCLUSION: Implementing a strategy of surfactant administration by transient intubation during nCPAP reduces the need for MV without adverse effects on outcome and may be an option to more effectively treat RDS, particularly in a care setting where transfer is necessary to provide MV.

Helicobacter pylori eradication in children and adolescents by a once daily 6-day treatment with or without a proton pump inhibitor in a double-blind randomized trial.

AIM: To evaluate two simplified Helicobacter pylori eradication treatment alternatives for children and adolescents. METHODS: Study subjects were identified by enzyme-linked immunosorbent assay and immunoblot in a family screening project. Helicobacter pylori infected 10-21 year olds were offered treatment, individuals with abdominal pain underwent upper endoscopy and those with peptic ulcers were excluded. Participants were randomized to either azithromycin 500 mg daily and tinidazole 500 mg two tablets daily in combination with lansoprasole 30 mg daily for 6 days (ATL-group) or with placebo (ATP-group). Urea Breath Test was performed at inclusion and after a minimum of 6 weeks after end of therapy. RESULTS: In total, 131 individuals were randomized, of whom 31 (24%) had undergone upper endoscopy. Full compliance was achieved in 93% (122 of 131). The intention-to-treat eradication rate was 67% (44 of 66) and 58% (38 of 65) for the ATL- and the ATP-group, respectively. CONCLUSION: The double-blind randomized clinical trial did not identify a simplified, successful once daily H. pylori treatment for children and adolescents. Thus, twice daily proton pump inhibitor (PPI)-based triple therapies for 7 days remain as the choice of treatment in children. Further, powerful and controlled studies are needed to elucidate the best treatment strategies for H. pylori eradication in this age group.

Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome.

BACKGROUND: Both prophylactic and early surfactant replacement therapy, compared with later selective surfactant administration, reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS). However, continued post-surfactant intubation and ventilation are risk factors for chronic lung disease. Whether prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation reduces the need for mechanical ventilation and the incidence of chronic lung disease is unknown. OBJECTIVES: To compare two treatment strategies in preterm infants with, or at risk for, RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation, vs later, selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966-December 2003), CINAHL (1982-December 2003), EMBASE (1980-December 2003), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), Pediatric Research (1990-2003), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation, vs selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, time in oxygen, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. MAIN RESULTS: Four randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.70, 95% CI 0.59, 0.84]. None of the trials reported a significant difference in the incidence of BPD or CLD; however, meta-analysis for this outcome cannot yet be performed because the primary data from three of the trials have not yet been published in full. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.59, 95% CI 1.35, 1.88]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.51 doses per patient, 95% CI 0.36, 0.65]. Trends towards a decreased incidence of air leak syndromes (two studies) and a higher incidence of patent ductus arteriosus requiring treatment (one study) were seen in the early surfactant group. There was no evidence of effect on time in oxygen or duration of mechanical ventilation. REVIEWERS' CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later, selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. There is insufficient evidence at present to reliably evaluate effect on BPD or CLD.

Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for RDS.

BACKGROUND: Both early and prophylactic surfactant replacement therapy compared with later selective surfactant administration reduces mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS). Continuous distending pressure (CDP) has also been shown to improve clinical outcomes in preterm infants with RDS. OBJECTIVES: To compare two treatment strategies in preterm infants with, or at risk for, RDS: early surfactant administration with brief mechanical ventilation (less than 1 hour) followed by extubation, vs later, selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966-December 2001), CINAHL (1982-December 2001), EMBASE (1980-December 2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), Pediatric Research (1990-2001), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation, vs selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD, need for oxygen at 28 days of age), incidence of chronic lung disease (CLD, need for oxygen at 36 weeks' post-conceptional age), mortality (neonatal mortality < 28 days and mortality prior to hospital discharge), duration of mechanical ventilation, duration of hospitalization, time in oxygen, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), incidence of pulmonary hemorrhage, and other complications of prematurity. Data analyses were performed in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Only one randomized controlled clinical trial met selection criteria and was included in this review (Verder 1994). In this study of infants with signs of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later, selective surfactant administration was associated with a lower incidence of mechanical ventilation (ventilation continuing for one hour or more after surfactant administration in the early surfactant group or initiated for respiratory insufficiency or apnea in either group [RR 0.51, 95% CI 0.32, 0.76]). A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [RR 1.74, 95% CI 1.30, 2.33]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [MD 0.51, 95% CI 0.32, 0.70]. Trends towards a decreased incidence of mortality, and a higher rate of patent ductus arteriosus requiring treatment were seen in the early surfactant group. There was no evidence of effect on median time in oxygen, duration of mechanical ventilation, or incidence of BPD (oxygen at 28 days). REVIEWER'S CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later, selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. These conclusions are based on findings from one small randomized clinical trial. Additional randomized trials are needed and are underway.

Cytokine response in cerebrospinal fluid from preterm infants with posthaemorrhagic ventricular dilatation.

AIM: Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and neurological disability in the preterm infant. Proinflammatory cytokines have been implicated in the pathogenesis of white matter injury and subsequent cerebral palsy. The aim of this study was to determine the levels of proinflammatory cytokines in cerebrospinal fluid (CSF) from preterm infants with PHVD and to correlate the levels to white matter damage and neurodevelopmental outcome. METHODS: CSF samples were obtained from 24 preterm infants with expanding PHVD and 19 preterm infants with normal ultrasound. Tumour necrosis factor-alphaa (TNF-alpha ), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) in CSF were measured by enzyme-linked immunosorbent assay, and IL-6 was measured by bioassay. RESULTS: The concentrations of TNF-alpha, IL-1beta, IL-6 and IL-8 were significantly elevated in CSF from infants with PHVD. TNF-alpha was detected in 43% of PHVD infants and 11% of controls (p = 0.04). IL-1beta was detected in 67% of PHVD infants and 0% of controls (p < 0.0001). The concentrations of IL-6 were 368 (145-460) pg ml(-1) in the PHVD group and 30 (25-41) pg ml(-1) in the control group (p < 0.0001), and those of IL-8 were 3000 (1620-3400) pg ml(-1) in the PHVD group and 35 (0-230) pg ml(-1) in the control group (p < 0.0001). Cytokine concentrations did not correlate with white matter lesions on ultrasound, shunt dependence or neurological outcome within the PHVD group. CONCLUSION: There was an intense and prolonged inflammatory reaction in CSF from preterm infants with PHVD and a high risk for subsequent white matter injury and permanent neurological impairment.

Brain-specific proteins in the cerebrospinal fluid of severely asphyxiated newborn infants.

UNLABELLED: Upcoming trials of neuroprotective strategies in severely asphyxiated newborn infants emphasize the need for early and objective markers of both good and bad long-term prognosis. Traditional markers such as neurological depression and seizures are not specific. AIM: To study whether measurement in the cerebrospinal fluid of some proteins known to be specific to the central nervous system was in covariance with the clinical course and long-term prognosis. METHODS: Twenty-two asphyxiated infants were included in the study and compared with a control group of 8 infants without signs of perinatal asphyxia. Cerebrospinal fluid (CSF) was collected during the first 4 d of life and analysed for neurofilament protein (NFp), glial fibrillary acidic protein (GFAp), protein S-100 and neuron-specific enolase (NSE). RESULTS: The concentrations of all four proteins were significantly increased in the CSF of asphyxiated infants. The concentrations correlated significantly with other indicators of long-term prognosis and to neurological impairment at I y of age, or death before that time. Specifically, concentrations were excessively high in the five infants who died. CONCLUSIONS: High concentrations of brain-specific proteins are released into the CSF of asphyxiated infants. It might therefore be useful to measure these concentrations when excluding patients with the gravest prognosis from neuroprotective trials.

Helicobacter pylori infection in Swedish school children: lack of evidence of child-to-child transmission outside the family.

BACKGROUND & AIMS: Helicobacter pylori infection is mainly acquired in early childhood, but the exact routes of transmission remain elusive. To distinguish between risks of intrafamilial and extraneous child-to-child transmission, we studied H. pylori seroprevalence among Swedish school children with varying family backgrounds. METHODS: In a cross-sectional study, 695 of 858 (81%) 10-12-year-olds in 36 school classes in Stockholm donated blood and answered a questionnaire. Infection was detected by enzyme-linked immunosorbent assay and confirmed by immunoblot and urea breath test. RESULTS: Overall, 112 (16%) children were infected. The seroprevalence was 2% among 435 children with Scandinavian parents and 55% among 144 children with origin in high prevalence areas (Middle East and Africa). Among children born in Scandinavia, the odds ratios (adjusted for gender, socioeconomic status, and family size) for being seropositive were 39.1 (95% confidence interval, 16.7-91.3) and 5.6 (1.8-17.3) when having parents born in high and medium prevalence areas, respectively, relative to children with Scandinavian parents. Importantly, the prevalence of infection among the classmates was not a risk factor for H. pylori infection. CONCLUSION: Our data indicate that intrafamilial transmission is far more important than child-to-child transmission outside the family. The H. pylori prevalence in the parental generation may be a crucial determinant for the child's risk of contracting the infection.

Brain specific proteins in posthaemorrhagic ventricular dilatation.

Median neurofilament and glial fibrillary acidic protein concentrations in the cerebrospinal fluid of 18 infants with posthaemorrhagic ventricular dilatation were 20-200 times higher than control values. S-100 protein in cerebrospinal fluid was four times higher than control values. Glial fibrillary acidic protein concentrations correlated with death or disability and with parenchymal lesions but not with shunt dependence.