Risk Of Patent Ductus Arteriosus Research Articles

Diuretics for respiratory distress syndrome in preterm infants.

Lung edema may complicate respiratory distress syndrome (RDS) in preterm infants. The aim of this review was to assess the risks and benefits of diuretic administration in preterm infants with RDS. The standard search method of the Cochrane Neonatal Review Group was used. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE and EMBASE were searched. These searches were updated in April 2003, March 2007, January 2011. In addition, the abstract books of the American Thoracic Society and Society for Pediatric Research were searched. MEDLINE and CENTRAL search was conducted using the keyword "Respiratory Distress Syndrome" alone, to find studies of medications recently classified as diuretics, such as theophylline. In addition, EMBASE, controlled-trials.com and clinicaltrials.gov searches were completed in January 2011. MEDLINE search updated to August 2011. Trials were included in which preterm infants with RDS and less than five days of age were randomly allocated to diuretic administration. Of those trials, studies were only included in which at least one of the following outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic shock, intraventricular hemorrhage, renal failure, duration of oxygen supplementation, duration of mechanical ventilation, need for oxygen supplementation at 28 days of life, oxygen supplementation at 36 weeks of postmenstrual age (gestational age + postnatal age), length of stay, number of rehospitalizations during the first year of life, and neurodevelopmental outcome. The standard method for the Cochrane Collaboration, which is described in the Cochrane Collaboration Handbook, was used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. Seven studies met inclusion criteria. Six studies using furosemide were done before the current era of prenatal steroids, surfactant and fluid restriction. Furosemide administration had no long-term benefits. Furosemide-induced transient improvement in pulmonary function did not outweigh an increased risk for patent ductus arteriosus and for hemodynamic instability. In one recent study, theophylline had no long-term benefits. Theophylline significantly decreased the risk of oligoanuria and transiently increased renal function, but did not significantly affect renal function at discharge or other outcomes. There are no data to support routine administration of furosemide in preterm infants with RDS. Elective administration of furosemide to any patient with RDS should be carefully weighed against the risk of precipitating hypovolemia or developing a symptomatic patent ductus arteriosus. There are not enough data to support routine administration of low-dose theophylline in preterm infants with RDS.

Cochrane Review: Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants

AbstractBackgroundMost premature infants are not sufficiently mature physiologically to ingest all of their required water and nutrients orally. Therefore, premature infants rely on their caregivers to regulate their volume of water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants.ObjectivesTo determine the effect of water intake on postnatal weight loss, the risks of dehydration, and other morbidities and mortality in premature infants.Search strategyRandomized clinical trials (RCTs) identified in previous versions of this review were re‐examined and, in each case, retained. Additional trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a list of trials provided by the Cochrane Neonatal Review Group, with a PubMed search, and in the authors' personal files.This search was updated in 2010.Selection criteriaOnly RCTs of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by intravascular infusion.Data collection and analysisStandard methods of the Cochrane Collaboration were used. Study selection and data abstraction was performed independently by each reviewer. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk and risk difference were computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed.Main resultsThe analysis of the five studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus and necrotizing enterocolitis. With restricted water intake, there are trends toward increased risk of dehydration and reduced risks of bronchopulmonary dysplasia, intracranial hemorrhage, and death, but these trends are not statistically significant.Authors' conclusionsBased on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis without significantly increasing the risk of adverse consequences.Plain Language SummaryRestricted versus liberal water intake for preventing morbidity and mortality in preterm infantsMost babies born before 37 weeks of pregnancy (preterm babies) are not developed enough to take all the water and nutrients they need by mouth. As a result, they are unable to regulate their intake of water. Inadequate water intake can cause the baby to become dehydrated. Excessive water intake can cause heart and lung problems or intestinal damage. Systematic review of trials related to this issue leads to the conclusion that careful restriction of water for preterm babies, to amounts that meets their physical needs without causing dehydration, reduces the risk of certain complications. More research on this topic is needed.

Diuretics for very low birth weight infants in the first 28 days: a survey of the US neonatologists

The objective of this study was to describe factors influencing diuretic use by neonatologists caring for very low birth weight neonates. We surveyed 400 U.S. neonatologists. Respondents made therapeutic decisions in clinical scenarios involving very low birth weight infants at 7, 14 and 28 days of age. Response rate was 39%. Diuretic therapy was chosen in 31% of scenario decisions, with pro re nata dosing selected early and regular dosing more common at later ages. Diuretic use was strongly associated with method of respiratory support, and was chosen less often by those also choosing fluid restriction and those concerned about patent ductus arteriosus risk. After adjusting for these factors, excessive weight gain, expected improvement in work of breathing and expected decrease in ventilator days were also associated with diuretic use. The extent of and expectations for diuretic therapy by neonatologists caring for very low birth weight neonates may exceed evidence for efficacy.

Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants.

Respiratory distress syndrome (RDS) is caused by a deficiency or dysfunction of pulmonary surfactant. A variety of surfactant products including protein free synthetic surfactant have been developed and tested in the prevention and treatment of RDS. To assess the effect of prophylactic administration of protein free synthetic surfactant (SS) on mortality, chronic lung disease and other morbidities associated with prematurity in preterm newborns at risk for developing RDS. Subgroup analysis were planned according to the degree of prematurity, surfactant product and dosage schedule. Searches were made of the The Cochrane Library, MEDLINE, OVID, EMBASE, CINAHL from 1966 to 2009. In addition, previous reviews including cross references and abstracts from the Society for Pediatric Research were searched. No language restrictions were applied. Randomized and quasi-randomized controlled trials that compared the effect of protein free SS administered to high risk preterm newborns at or shortly after birth in order to prevent RDS, mortality and complications of prematurity. Data regarding clinical outcomes was excerpted from the clinical trials by the reviewers. Data were analyzed according to the standards of the Cochrane Neonatal Review Group. Studies of prophylactic administration of protein free SS note a variable improvement in the respiratory status and a decrease in respiratory distress syndrome in infants who receive prophylactic protein free SS. The meta-analysis supports a decrease in the risk of pneumothorax (typical relative risk 0.67, 95% CI 0.50, 0.90), pulmonary interstitial emphysema (typical relative risk 0.68, 95% CI 0.50, 0.93), and neonatal mortality (typical relative risk 0.70, 95% CI 0.58, 0.85). No differences were seen in the risk of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and cerebral palsy. The meta-analysis supports an increase in the risk of patent ductus arteriosus associated with prophylactic SS administration (typical relative risk 1.11, 95% CI 1.00, 1.22), and an increase in the risk of pulmonary hemorrhage (typical relative risk 3.28, 95% CI 1.50, 7.16). Prophylactic intratracheal administration of protein free synthetic surfactant to infants at risk of developing respiratory distress syndrome has been demonstrated to improve clinical outcome. Infants who receive prophylactic protein free SS have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema, and a decreased risk of neonatal mortality. Infants who receive prophylactic protein free SS have an increased risk of developing patent ductus arteriosus and pulmonary hemorrhage.

Chronic In Utero Cyclooxygenase Inhibition Alters PGE2-Regulated Ductus Arteriosus Contractile Pathways and Prevents Postnatal Closure

Although prostaglandin E2 (PGE2) vasodilates the ductus arteriosus, tocolysis with cyclooxygenase (COX) inhibitors delays postnatal ductus arteriosus closure. We used fetal mice and sheep to determine whether PGE2 has a role in the development of ductus contractility that is distinct from its function as a vasodilator. Prolonged exposure of fetal ductus to PGE2 in vitro increased the expression of CaL- and K+-channel genes (CaLalpha1c, CaLbeta2, Kir6.1, and Kv1.5, which regulate oxygen-induced constriction) without affecting the genes that regulate Rho-kinase-mediated calcium sensitization. Conversely, chronic exposure to COX inhibitors in utero decreased expression of CaL- and K+-channel genes, without affecting Rho-kinase-associated genes. Chronic COX inhibition in utero decreased the ductus' in vitro contractile response to stimuli that use CaL- and K+-channels (like O2 and K+), whereas the response to stimuli that act through Rho-kinase-mediated pathways (like U46619) was not significantly affected. Phosphodiesterase expression, which decreases the ductus' sensitivity to cAMP- or cGMP-dependent vasodilators, was increased by PGE2 exposure and decreased by COX inhibition, respectively. These studies identify potential downstream effectors of a PGE2-mediated, developmental program, regulating oxygen-induced ductus closure. Alterations in these effectors may explain the increased risk of patent ductus arteriosus (PDA) after in utero COX inhibition.

Animal derived surfactant extract for treatment of respiratory distress syndrome

Respiratory distress syndrome (RDS) is caused by a deficiency or dysfunction of pulmonary surfactant. A wide variety of surfactant products have been formulated and studied in clinical trials. These include synthetic surfactants and animal derived surfactant extracts. Trials of surfactant replacement have either tried to prevent the development of respiratory distress in high-risk premature infants or treat established respiratory distress in premature infants. To assess the effect of administration of animal derived surfactant extract on mortality, chronic lung disease and other morbidities associated with prematurity in preterm infants with established respiratory distress syndrome. Subgroup analysis were planned according to the specific surfactant product, the degree of prematurity, and the severity of disease. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and CINAHL from 1975 through December 2008. In addition, searches were made of previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants and journal hand searching in the English language. Randomized or quazi-randomized controlled trials that compared the effect of animal derived surfactant extract treatment administered to infants with established respiratory distress syndrome in order to prevent complications of prematurity and mortality. Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. Thirteen randomized controlled trials were included in the analysis. The studies demonstrated an initial improvement in respiratory status (improved oxygenation and decreased need for ventilator support). The meta-analysis supports a significant decrease in the risk of any air leak (typical relative risk 0.47, 95% CI 0.39, 0.58; typical risk difference -0.16, 95% CI -0.21, -0.12), pneumothorax (typical relative risk 0.42, 95% CI 0.34, 0.52; typical risk difference -0.17, 95% CI -0.21, -0.13), and a significant decrease in the risk of pulmonary interstitial emphysema (typical relative risk 0.45, 95% CI 0.37, 0.55; typical risk difference -0.20, 95% CI -0.25, -0.15). There is a significant decrease in the risk of neonatal mortality (typical relative risk 0.68, 95% CI 0.57, 0.82; typical risk difference -0.09, 95% CI -0.13, -0.05), a significant decrease in the risk of mortality prior to hospital discharge (typical relative risk 0.63, 95% CI 0.44, 0.90; typical risk difference -0.10, 95% CI -0.18, -0.03) and a significant decrease in the risk of bronchopulmonary dysplasia (BPD) or death at 28 days of age (typical relative risk 0.83, 95% CI 0.77, 0.90; typical risk difference -0.11, 95 CI -0.16, -0.06). No differences are reported in the risk of patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, BPD or retinopathy of prematurity. Infants with established respiratory distress syndrome who receive animal derived surfactant extract treatment have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema, a decreased risk of mortality, and a decreased risk of bronchopulmonary dysplasia or death.

Can Early Echocardiographic Findings Predict Patent Ductus Arteriosus?

Background: Prophylactic treatment with prostaglandin synthetase inhibitors (PSI) is potentially harmful. Moreover, long-term benefits of prophylactic use of indomethacin or ibuprofen are not proven. Early treatment of a high-risk population is alternative to the routine prophylactic use of PSI, but it remains unclear which newborn is at greatest risk for patent ductus arteriosus (PDA). Objective: Evaluation of the prognostic value of early echocardiographic studies with respect to PDA in later life. Methods: Sixty preterm infants with a mean birth weight of 1,087 g and mean gestational age of 28.5 weeks were included in a prospective study. Cardiac scans were performed in all newborns on entry into the study (within 12–48 h after birth) and further in case of clinical suspicion of PDA or obligatorily on the 7th and 28th days of life. There was no prophylactic or treatment use of any PSI during the study period. Newborns were divided into 2 cohorts: with significant left to right shunt requiring surgical ligation of PDA (n = 16) or without significant PDA during follow-up (control group, n = 44). Results: On entry, the mean internal diameter of the ductus arteriosus (2.6 vs. 0.91 mm/kg; p < 0.01), mean cardiac index across aortic valve (2.96 vs. 2.37 l/min/m²; p < 0.01) and early filling peak velocity (43.1 vs. 33.7; p = 0.01) were significantly higher in babies who later needed surgical ligation of PDA. There was no difference in the mean values of the other echocardiographic parameters studied. An early ductal diameter of >1.5 mm/kg predicted symptomatic PDA with a sensitivity of 94% and a specificity of 73%, and its positive predictive value equaled 57% and negative predictive value amounted to 97%. Conclusions: Early echocardiographic studies possess negative predictive value and may decrease unnecessary surgical ligation of PDA in very low birth weight infants.

Fluid regimens and the risk of patent ductus arteriosus in extremely low birth weight infants

Fluid regimens and the risk of patent ductus arteriosus in extremely low birth weight infants

Fluid regimens and the risk of patent ductus arteriosus in extremely low birth weight infants

Fluid regimens and the risk of patent ductus arteriosus in extremely low birth weight infants

Prevention and 18-Month Outcomes of Serious Pulmonary Hemorrhage in Extremely Low Birth Weight Infants: Results From the Trial of Indomethacin Prophylaxis in Preterms

A patent ductus arteriosus is a risk factor for pulmonary hemorrhage; however, despite halving the incidence of patent ductus arteriosus, indomethacin prophylaxis did not reduce the rate of pulmonary hemorrhage in the Trial of Indomethacin Prophylaxis in Preterms. Inclusion of mild bleeds after trauma to the upper airways may have masked a beneficial drug effect. Using the Trial of Indomethacin Prophylaxis in Preterms database, we studied the effect of prophylactic indomethacin on the prevention of serious hemorrhages in extremely low birth weight infants. We also compared the 18-month outcomes of infants with and without a serious pulmonary bleed. Pulmonary hemorrhage was classified as serious when it was treated with increased ventilator support, a higher concentration of oxygen, or transfusion of blood products. The cumulative risk for serious pulmonary hemorrhage was estimated for the first week of life and for the entire NICU stay. Poor outcome at a corrected age of 18 months was death or survival with cerebral palsy, cognitive delay, blindness, and/or deafness. A total of 123 (10.2%) of 1202 infants developed a serious pulmonary hemorrhage. During week 1, prophylactic indomethacin reduced the risk for serious pulmonary hemorrhage by 35%; however, during the entire NICU stay, the risk for such hemorrhages was decreased by only 23%. A reduced risk for patent ductus arteriosus explained 80% of the beneficial effect of prophylactic indomethacin on serious pulmonary bleeds. The risks for death or for survival with neurosensory impairment were doubled after a serious pulmonary hemorrhage. Extremely low birth weight infants with serious pulmonary hemorrhage have an increased risk for poor long-term outcome. Prophylactic indomethacin reduces the rate of early serious pulmonary hemorrhage, mainly through its action on patent ductus arteriosus. Prophylactic indomethacin is less effective in preventing serious pulmonary hemorrhages that occur after the first week of life.

Fluid regimens in the first week of life may increase risk of patent ductus arteriosus in extremely low birth weight infants

High fluid volumes may increase neonatal morbidity. However, evidence supporting fluid restriction is inconclusive and restricting fluids may restrict caloric intake. To determine if higher fluid intake was associated with increased risk of patent ductus arteriosus (PDA) or bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. A total of 204 ELBW (<or=32 weeks, <or=1250 g) infant survivors were grouped into low-, intermediate- and high-fluid groups. chi2 analyzed proportions of subjects with and without morbidities across groups. Logistic regression quantified increased risk of PDA or BPD associated with fluid intake while controlling for confounders. Analysis of variance compared differences in caloric intake across groups. After controlling for gestational age, severity of illness and weight change, fluid intake on day 2 (odds ratio (OR) 1.014; confidence interval (CI) 1.001 to 1.028) and day 3 (OR 1.022; CI 1.004 to 1.040) was associated with increased risk of PDA. High fluid intake (>170 ml kg(-1) day(-1)) in the first days of life is associated with increased risk of PDA.

288 The Effect of Second Course of Antenatal Betamethasone (BM) on Neonatal Morbidity in Preterm Infants: A Randomized Trial

Background: Single course of BM decreases neonatal morbidity when administrated within 7 days before preterm delivery. The benefits of second course of BM are unknown.Aims: To evaluate the efficacy of second course of BM in increasing the intact survival of preterm infants.Methods: In this randomized, blinded trial, pregnant women (before 34.0 gestational weeks) were eligible if they had remained undelivered more than 7 days after antenatal BM. Single dose of BM (12 mg) or placebo was given, when the preterm delivery was anticipated. Primary outcome was intact survival without respiratory distress syndrome and/or intracerebral hemorrhage (grade 3–4).Results: 251 mothers participated the study. All infants were delivered prior to 35 weeks of gestation. At present the outcome of 285 infants has been analyzed. The intact survival was 48% in BM and 58% in placebo groups (P=0.1). The intact survival was non-significantly higher in BM group (58% vs. 41%, P=0.3), when the study drug was administered more than 24 h before birth (group 1). The incidence of intact survival was lower in BM group (44% vs. 61%, P=0.01), when the intervention took place less than 24 h before birth (group 2). In group 1, the risk of patent ductus arteriosus was 16% in BM and 41% in placebo group (P=0.04), vs. 29% and 27% in group 2. In group 2, systolic and diastolic blood pressures were increased in BM arm (P=0.02 and P=0.03). In group 1, blood pressure levels were similar between study groups. The second course of BM did not influence the acute outcome of preterm infants. The preterm infants benefited from antenatal BM, when treatment was given more than 24 h before delivery. BM given less than 24 hours before delivery was associated with increased blood pressure after birth and with a decrease in intact survival.

Angiotensin II type 1 receptor A1166C polymorphism and prophylactic indomethacin treatment induced ductus arteriosus closure in very low birth weight neonates.

Altered pulmonary vascular resistance might be a factor for delayed closure of the ductus arteriosus (DA) in preterm infants. Angiotensin II plays a central role in the elevation of pulmonary vascular resistance. Angiotensin II exerts its vasoconstrictor effect on the angiotensin II type 1 receptor (AT1R). Homozygous carriers of the AT1R A1166C genetic variant present an exaggerated vasoconstrictor response to angiotensin II. We have investigated whether the presence of AT1R CC1166 influences the effect of prophylactic indomethacin treatment on the closure of DA until the fifth postnatal day in preterm infants. In this retrospective study detailed medical history of the first postnatal week was obtained in 159 infants born before the 33rd gestational week. All were treated by prophylactic indomethacin to induce permanent closure of the DA. On the sixth postnatal day the DA was still open in 56, whereas it was permanently closed in 103. The AT1R A1166C genotype of the infants was determined from Guthrie spots. Stepwise binary logistic regression analysis was used to assess the effect of medical conditions and genotype on the risk of patent DA (PDA). Birth weight, infantile respiratory distress, and severe hypotension were independent risk factors for PDA (p < 0.01, p < 0.05, p < 0.05, respectively). The carrier state of AT1R CC1166 was protective against PDA (p < 0.05; odds ratio, 0.067). AT1R AC1166 genotype was not associated with PDA. Our results indicate that the risk of PDA might be lower in infants of AT1R CC1166 than in those with AC or AA genotypes.

Bronchopulmonary dysplasia: an enduring challenge.

1. Yvonne E. Vaucher, MD, MPH* 1. *Clinical Professor of Pediatrics, Division of Neonatology, University of California, San Diego, Calif. After completing this article, readers should be able to: 1. Describe the most common cause of chronic lung disease during infancy. 2. Explain the importance of a history of bronchopulmonary dysplasia throughout childhood. 3. Identify infants at high risk for developing bronchopulmonary dysplasia. 4. List the adverse effects associated with postnatal corticosteroids. Despite clinical advances in antepartum, intrapartum, and neonatal care, bronchopulmonary dysplasia (BPD) continues to challenge infants who have been in neonatal intensive care units and their caretakers. BPD is the most common cause of chronic respiratory disease during infancy and remains a major cause of long-term medical, pulmonary, and neurodevelopmental morbidity, increasing the cost of health care and the utilization of medical and educational resources throughout childhood. BPD is a clinical diagnosis, defined by oxygen dependence for a specific period of time after birth and accompanied by characteristic radiographic findings that correspond to anatomic abnormalities. Thus far, a precise physiologic definition of BPD is lacking. As the clinical presentation has evolved over the past 30 years, so has the definition. As originally described by Northway in the 1960s, the diagnosis of classic BPD was based on progressive radiographic changes in preterm infants who were treated for severe respiratory distress syndrome (RDS) immediately after birth and had prolonged ventilator and oxygen dependence. This form of BPD occurred in larger, relatively mature preterm infants, who required treatment with high-pressure mechanical ventilation and high concentrations of oxygen. Although the acute respiratory disease initially improved in these infants, oxygen requirements increased 7 to 10 days after birth and persisted for at least 28 days. The definition of BPD subsequently was modified by Bancalari to include preterm infants who had less severe RDS that initially required short-term mechanical ventilation, but who also developed persistent respiratory symptoms and an oxygen requirement for at least 28 days after birth …

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants.

Most premature infants are not sufficiently mature physiologically to take all of their required water and nutrients orally, and so they cannot regulate their own water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. The objective of this review is to examine the effects of water intake on postnatal weight loss and on the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. Randomized clinical trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a previous review by one of the authors (Bell EF. Fluid therapy. In: Effective Care of the Newborn Infant, eds JC Sinclair, MB Bracken. Oxford: Oxford University Press, 1992: 59-72, approximately approximately Bell 1992 approximately approximately ), in a list of trials provided by the Cochrane Neonatal Review Group, and in the authors' personal files. Only randomized clinical trials of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by parenteral means. Studies were included regardless of outcomes examined. Trials were selected by two reviewers, who also assessed the methodological quality of each trial. Data were independently extracted by the reviewers, and differences were reconciled. The data were then entered into tables using RevMan 3.1 for Windows. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk was computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed. The analyses (including calculation of relative risk, risk difference, and weighted mean difference) and tests of heterogeneity were accomplished with MetaView 3.1 software and a fixed effects model. No subgroup analyses were conducted. The analysis of the four studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus, necrotizing enterocolitis, and death. With restricted water intake, there are trends toward increased risk of dehydration and reduced risk of bronchopulmonary dysplasia, but these trends are not statistically significant. Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis--and perhaps the overall risk of death--without significantly increased risk of adverse consequences.

Diuretics for respiratory distress syndrome in preterm infants.

Lung edema may complicate respiratory distress syndrome (RDS) in preterm infants. The aim of this review was to assess the risks and benefits of diuretic administration in preterm infants with RDS. We used the standard search method of the Cochrane Neonatal Review Group. We searched Medline, Embase and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: <exp respiratory distress syndrome> and <exp diuretics>. In addition, we searched the abstract books of the American Thoracic Society and Pediatric Research Societies. We only included trials in which preterm infants with RDS and less than 5 days of age were randomly allocated to diuretic administration. Of those trials, we only included studies in which at least one of the following outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic shock, intraventricular hemorrhage, renal failure, duration of oxygen supplementation, duration of mechanical ventilation, need for oxygen supplementation at 28 days of life, oxygen supplementation at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, number of rehospitalizations during the first year of life, and neurodevelopmental outcome. We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. Six studies met inclusion criteria. Studies available for this systematic review were all done before the current era of prenatal steroids, surfactant, indomethacin and fluid restriction. Furosemide administration had no long-term benefits. Furosemide-induced transient improvement in pulmonary function did not outweigh an increased risk for patent ductus arteriosus and for hemodynamic instability. There are no current data to support routine diuretic administration in preterm infants with RDS. Elective administration of furosemide or any diuretic to any patient with RDS should be carefully weighed against the risk of precipitating hypovolemia. In addition, elective administration of furosemide should be weighed against the risk of developing a symptomatic patent ductus arteriosus.

Prophylactic synthetic surfactant for preventing morbidity and mortality in preterm infants.

This section is under preparation and will be included in the next issue. To assess the effect of prophylactic administration of synthetic surfactant in preterm newborns at risk for developing respiratory distress syndrome (RDS). Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infants; publication type, clinical trial), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language. Randomized, controlled trials which compared the effect of prophylactic synthetic surfactant administered to high risk preterm newborns at or shortly after birth in order to prevent respiratory distress syndrome and other complications of prematurity. Data regarding clinical outcomes including the incidence of pneumothorax, pulmonary interstitial emphysema, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (any grade and severe intraventricular hemorrhage), bronchopulmonary dysplasia, mortality, bronchopulmonary dysplasia or death, retinopathy of prematurity (any retinopathy, and retinopathy stages 3-4) mortality to one year of age, and cerebral palsy was excerpted from the report of the clinical trials by the reviewer. Data were analyzed according to the standards of the Cochrane Neonatal Review Group. Studies of prophylactic administration of synthetic surfactant note a variable improvement in the respiratory status and a decrease in respiratory distress syndrome in infants who receive prophylactic synthetic surfactant. The meta-analysis supports a decrease in the risk of pneumothorax (typical relative risk 0.67, 95% CI 0.50, 0.90; typical risk difference -0.05, 95% CI -0.09, -0. 02), a decrease in the risk of pulmonary interstitial emphysema (typical relative risk 0.68, 95% CI 0.50, 0.93; typical risk difference -0.06, 95% CI -0.11, -0.01), and a decrease in risk of neonatal mortality (typical relative risk 0.70, 95% CI 0.58, 0.85; typical risk difference -0.07, 95% CI -0.11, -0.03). No differences were seen in the risk of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and cerebral palsy. The meta-analysis supports an increase in the risk of patent ductus arteriosus associated with prophylactic synthetic surfactant administration (typical relative risk 1.11, 95% CI 1.00, 1.22; typical risk difference 0.05, 95% CI 0. 00,0.10), and an increase in the risk of pulmonary hemorrhage (typical relative risk 3.28, 95% CI 1.50, 7.16; typical risk difference 0.03, 95% CI 0.01, 0.05). Prophylactic intratracheal administration of synthetic surfactant to infants judged to be at risk of developing respiratory distress syndrome has been demonstrated to improve clinical outcome. Infants who receive prophylactic synthetic surfactant have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema, and a decreased risk of neonatal mortality. Infants who receive prophylactic synthetic surfactant have an increased risk of developing patent ductus arteriosus and pulmonary hemorrhage.

The Relation of Maternal Complications to Outcomes in Very Low Birthweight Infants in an Era of Changing Neonatal Care

We examine the relation of key neonatal outcomes to pregnancy complications and to the use of antenatal steroids and investigate whether there is evidence of recent change in this relation. Complete information on pregnancy and neonatal course was available for 749 out of 949 singleton births without major congenital anomalies below 1501 g admitted to seven regional neonatal intensive care units between August 1, 1988 and June 30, 1991. Mortality was highest in infants born after labor with spontaneous rupture of fetal membranes of less than 24 hours duration (odds ratio [OR] = 1.6, 95% confidence interval [1.0, 2.6]). Spontaneous rupture of membranes of over 24 hours duration was associated with decreased risk of respiratory distress syndrome (OR = 0.42, [0.28, 0.64]) and decreased risk of patent ductus arteriosus (OR = 43, [0.28, 0.66]). Pregnancy induced hypertension was associated with increased risk of respiratory distress syndrome in those born at less than 20 weeks' gestation (OR = 6.0, [2.0, 17]). Labor with or without rupture of membranes of short duration was associated with increased risk of intraventricular hemorrhage (OR = 1.9, [1.2, 2.5]). These associations were not different in early versus late time periods of the study. Antenatal steroids were associated with dramatically reduced risk of mortality (OR = 0.20, [0.09, 0.50] ), respiratory distress syndrome (OR = 0.52, [0.32, 0.85]), and intraventricular hemorrhage (OR = 0.37, [0.21-0.65]).

Do survival and morbidity of very-low-birth-weight infants vary according to the primary pregnancy complication that results in preterm delivery?

This retrospective study was conducted to determine whether predischarge survival and morbidity of very-low-birth weight infants varied according to the principal pregnancy complication that led to preterm delivery. The hospital records of 535 consecutive live-born singleton infants who weighed between 500 and 1499 gm were reviewed, and five primary complications that resulted in preterm delivery were identified: (1) premature rupture of membranes (n = 244, 46%), (2) idiopathic preterm labor (n = 97, 18%), (3) antepartum hemorrhage (n = 58, 11%), (4) pregnancy-induced hypertension (n = 98, 18%), and (5) "other" complications (n = 38, 7%). Neonatal records were studied to identify the presence of respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary interstitial emphysema, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, and infant death before hospital discharge. Logistic regression analysis was used to analyze the association of each pregnancy complication with the various forms of neonatal morbidity. There were no statistically significant differences in discharge survival rates (range 71% to 88%) among infants born to women who experienced one of the five types of primary complications. Independent of all confounders, premature rupture of membranes was associated with a decreased risk of respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary interstitial emphysema, patent ductus arteriosus, and intraventricular hemorrhage. Preterm labor was associated with an increased risk of pulmonary interstitial emphysema, patent ductus arteriosus, and intraventricular hemorrhage. Pregnancy-induced hypertension was associated with an increased risk of respiratory distress syndrome, pulmonary interstitial emphysema, and patent ductus arteriosus. Antepartum hemorrhage was associated with an increased risk of patent ductus arteriosus. The principal pregnancy complication that led to preterm delivery significantly influenced predischarge morbidity but not the predischarge survival of live-born infants.

WATER—THE MAJOR NUTRIENT

Water metabolism is a major problem in infants of very low birth weight. Their surface is proportionally larger, they have a relatively low intracellular water volume and a high extracellular and total body volume. Kidney function is immature compared to bigger infants, and the neuroendocrine function is also immature. Finally the large surface and the high skin permeability causes a very high insensible water loss in the early neonatal period. Water imbalance presents itself as either dehydration or overhydration. Dehydration gives poor peripheral--and renal circulation and thereby decreased renal function with acidosis. Furthermore hyperosmolar dehydration will give increased hematocrit and blood viscosity and hyperbilirubinaemia. Excessive administration of water will give oedema and congestive heart failure and possibly an increased risk for patent ductus arteriosus, bronchopulmonal dysplasia and necrotising enterocolitis. The evaporative water losses varies according to the thermal environment and air humidity and it is therefore impossible to give narrow limits for the daily water intake. Clinical examination, frequent controls of body weight (twice daily) and measurements of urine volume and osmolarity serve as guide lines. Yet inappropriate secretion of ADH may confuse the value of measuring urine osmolarity. Finally a neonatal weight loss of 5-10% may be beneficial as a decrease in extracellular water may lessen the working load of the heart and therefore possibly lessen the risk for a patent ductus. Renal immaturity in handling sodium reabsorption on the other hand, will often give an excessive dehydration. For this reason about 2 mmol Na/kg body weight should be given daily to very low birth weight infants from the fourth day of life to the 3rd-4th week if the baby is on human milk or a low salt formula.