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.

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.

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.

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.

Adverse reactions and serologic response to a booster dose of acellular pertussis vaccine in children immunized with acellular or whole-cell vaccine as infants.

Adverse reactions and antibody response to pertussis toxin, ie, antitoxin, after a booster injection of an acellular pertussis vaccine were studied in 2-year-old children. A majority (212/241) of the children had previously been immunized with either two or three doses of the acellular vaccine at the ages of 6, 7, and 8 months. The other 29/241 children had received three doses of a plain whole-cell pertussis vaccine at the same ages. In the children who received primary immunization with the acellular vaccine, two cases of more serious systemic reactions occurred in close temporal association with the booster injection. Less serious systemic reactions were few. Local reactions were more common in the children only immunized with the acellular vaccine. Large reactions (greater than 10 cm) were only seen in this group. A good antitoxin response was elicited in both groups. The geometric mean titer in the former whole-cell vaccine recipients was significantly higher than in the children who received only acellular vaccine. The study raised some questions concerning differences in reactogenicity and immune response after a booster injection of an acellular vaccine depending on the type of pertussis vaccine given to infants for the primary immunization.

Primary immunization of infants with an acellular pertussis vaccine in a double-blind randomized clinical trial.

The rate of adverse reactions and the immunogenicity of a two-component acellular pertussis vaccine as compared with a plain whole-cell vaccine and a placebo were evaluated for primary immunization in 319 6-month-old infants in a double-blind randomized clinical trial. The acellular vaccine produced few and mild systemic and local reactions. Fever (greater than or equal to 38 degrees C) occurred in 6% to 8% of acellular vaccinees as opposed to 25% to 37% of whole-cell vaccinees. Redness (greater than or equal to 1 cm) appeared in 2% to 13% of the acellular vaccine and 24% to 32% of the whole-cell vaccine recipients. Antibody response to pertussis toxin measured in a neutralization test was obtained in 97% to 100% of the infants receiving either two or three doses of the acellular vaccine as compared to 59% after three doses of whole-cell vaccine.

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.

Sixteen-month follow-up of antibodies to pertussis toxin after primary immunization with acellular or whole cell vaccine.

Antibodies to pertussis toxin (antitoxin) were measured in three blood samples drawn during a 16- to 17-month follow-up of infants immunized with adsorbed two component acellular pertussis vaccine (JNIH-6) or plain whole cell vaccine. A significant decrease of antitoxin concentration was noted between each follow-up in the acellular vaccine groups (P less than 0.005). The higher antitoxin titers induced by three doses or by two doses spaced by 2 months compared with two doses with 1-month interval disappeared with time. The antitoxin titers among high responders to three doses of whole cell vaccine paralleled those of the acellular vaccinees but at a significantly lower level. Reported exposure to pertussis did not significantly alter the decrease of antitoxin titers. The study also showed that acellular pertussis vaccine induced an antitoxin response still measurable in greater than or equal to 97 and greater than or equal to 91% of samples drawn 10 to 11 and 16 to 17 months after primary immunization, respectively.

Long term serologic follow-up after pertussis immunization.

Neutralizing antibodies to pertussis toxin (antitoxin) were determined in 201 blood samples from 4-year-old children. They had received primary immunization at 6 to 8 months of age with an acellular (n = 149) or a whole cell (n = 52) pertussis vaccine and 195 of them had received a booster dose of the acellular vaccine 9 to 16 months later. Data on exposure to pertussis and occurrence of pertussis were also collected. There was a rapid decrease of antitoxin between immediate postbooster titers and those measured 24 months later. This decrease per month was significantly greater than that after the primary immunization series (P less than 0.001). Neither the number nor the spacing of acellular vaccine doses given for primary series influenced the titers found 24 months after the booster. An antitoxin response was still measurable in 86% of the 196 four-year-old children. None of 19 exposed children developed whooping cough, which suggested that the antibody concentrations during the follow-up period were sufficient for protection. The results indicate a need for long term follow-up studies in the evaluation of new vaccines and immunization schedules.

A ten year follow-up after immunization with a two component acellular pertussis vaccine.

OBJECTIVES: To investigate the duration of antitoxin response and immunity to pertussis 10 years after priming with either two or three doses of a two component acellular pertussis vaccine or with three doses of a whole cell vaccine and then boostered with the acellular vaccine. SUBJECTS: At 11 years of age 207 of 304 (68%) children of the original cohort returned for a blood sample and 262 (86%) participated by answering a questionnaire. METHODS: Neutralizing antibodies to pertussis toxin (antitoxin) were analyzed by the Chinese hamster ovary cell assay. Clinical pertussis and pertussis exposure were investigated by a structured questionnaire. RESULTS: Measurable antitoxin was found in 77% of the samples, with no differences by type of vaccine or by the number of doses given for priming. A significant decrease of antibody concentration (P<0.001) was noted from the previous recall at 4 years of age, and significant titer rises were found for 14% of the children, irrespective of known exposure. Confirmed pertussis during follow-up, as defined in the study, was reported for 14 of 262 (5%) children. CONCLUSIONS: The study showed that antitoxin concentrations are maintained in a situation of endemic pertussis and indicated that the long term protection after an acellular booster was good, irrespective of type of vaccine or the number of doses of acellular vaccine given for priming.

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.

Acute effects of two different doses of magnesium sulphate in infants with birth asphyxia.

The effects of two different doses of magnesium sulphate (MgSO4) were evaluated in a group of 15 full term infants with Apgar scores of < 6 at 10 minutes, studied within 12 hours of delivery. Seven infants received 400 mg/kg MgSO4 and eight received 250 mg/kg. After the larger dose, mean arterial pressure (MAP) fell by a mean of 6 mm Hg (13%) at one hour but was not significantly reduced thereafter. Respiratory depression lasted three to six hours. EEG readings and heart rate were not significantly different. Mean serum Mg2+ increased from 0.79 to 3.6 mmol/l at one hour. After 250 mg/kg MgSO4, MAP, EEG, tone and heart rate were unchanged. One infant developed transient respiratory depression. Mean serum Mg2+ rose from 0.71 to 2.42 mmol/l at one hour. MgSO4 (400 mg/kg) has an unacceptable risk of hypotension; 250 mg/kg MgSO4 was not associated with hypotension although respiratory depression can occur.

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.