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Vitamin A supplementation for preventing morbidity and mortality in very low birthweight infants.

BACKGROUND: Vitamin A is necessary for normal lung growth and the ongoing integrity of respiratory tract epithelial cells. Preterm infants have low vitamin A status at birth and this has been associated with increased risk of developing chronic lung disease. Several studies have been undertaken to assess whether vitamin A supplementation beyond that routinely given in multivitamin preparations can reduce the incidence of this outcome. OBJECTIVES: To assess the benefit of supplementation with vitamin A in very low birthweight infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, Cochrane Controlled Trials Register, and Science Citation Index. The reference lists of relevant trials, recent issues of paediatric and nutrition journals, abstracts and proceedings from relevant conferences in the English language were hand searched. SELECTION CRITERIA: Randomised controlled trials which compared the effects of supplemental vitamin A with standard vitamin A regimes in infants with birthweight </=1500g, and which reported clinical outcomes (death, chronic lung disease or bronchopulmonary dysplasia) and/or vitamin A concentrations were considered for the review. DATA COLLECTION AND ANALYSIS: Data on mortality, requirement for supplemental oxygen at one month of age and at 36 weeks post-menstrual age, retinopathy of prematurity and nosocomial sepsis were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Six eligible trials were identified, one having a much larger sample size than the others combined. The meta-analysis suggests supplementation with vitamin A results in benefit in terms of reducing oxygen requirement at 36 weeks post-menstrual age [summary RR 0.85 (0.73, 0.98), RD -8.5% (-15.9, -1.1), NNT 11.8 (6.3, 90.9)] and trends towards reduction in death or oxygen requirement at 36 weeks post-menstrual age [summary RR 0.89 (0.79, 1.00)], oxygen use in survivors at one month of age [summary RR 0.93 (0.86, 1.01)], and death or oxygen requirement at one month of age [summary RR 0.93 (0. 86, 1.00)]. Meta-analysis of the two studies which reported on retinopathy of prematurity suggests a trend towards reduced incidence in vitamin A supplemented infants. REVIEWER'S CONCLUSIONS: Supplementing very low birthweight infants with vitamin A is associated with a reduction in oxygen requirement amongst survivors at 36 weeks post-menstrual age. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in this outcome, balanced against the lack of other proven benefits and the acceptability of treatment. The benefits, in terms of vitamin A status, safety and acceptability of delivering vitamin A in an intravenous emulsion compared with repeat intramuscular injections should be assessed in a further trial.

Dietary Supplements↗

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

BACKGROUND: 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. OBJECTIVES: 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. SEARCH STRATEGY: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. REVIEWER'S CONCLUSIONS: 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.

Drinking↗

Prophylactic versus selective use of surfactant for preventing morbidity and mortality in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To compare the effect of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infants), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. SELECTION CRITERIA: Randomized controlled trials which compared the effects of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants were included in the analysis. DATA COLLECTION AND ANALYSIS: 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, and retinopathy of prematurity were excerpted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The majority of included studies noted an initial improvement in the respiratory status and a decrease in the incidence of respiratory distress syndrome in infants who received prophylactic surfactant. The meta-analysis supports a decrease in the incidence of pneumothorax, a decrease in the incidence of pulmonary interstitial emphysema, a decrease in the incidence of mortality and a decrease in the incidence of bronchopulmonary dysplasia or death associated with prophylactic administration of surfactant. No significant untoward effects of prophylactic surfactant administration are noted. REVIEWER'S CONCLUSIONS: Prophylactic surfactant administration to infants judged to be at risk of developing respiratory distress syndrome (intubated infants less than 30-32 weeks gestation) has been demonstrated to improve clinical outcome. Infants who receive prophylactic surfactant have a decreased incidence of pneumothorax, a decreased incidence of pulmonary interstitial emphysema and a decreased incidence of mortality. However, it remains unclear exactly which criteria should be used to judge "at risk" infants who would require prophylactic surfactant administration.

Humans↗

Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In preterm or low birth weight infants, does targeting ambient oxygen concentration to achieve a lower versus higher blood oxygen range, or administering restricted versus liberal supplemental oxygen, influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. An additional literature search was conducted of the MEDLINE, EMBASE, and CINAHL databases in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials in preterm or low birth weight infants utilising random or quasi-random patient allocation, in which ambient oxygen concentrations were targeted to achieve a lower versus higher blood oxygen range, or restricted versus liberal oxygen was administered, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the eligible trials was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The restriction of oxygen significantly reduced the incidence and severity of retinopathy of prematurity without unduly increasing death rates in the meta-analysis of the five trials included in this review. The one trial that specifically addressed the question of lower versus higher PaO2 found no effect on death, but did not report (in sufficient detail to warrant inclusion) the effect of this intervention on eye or other outcomes. The effects of either of these oxygen administration policies on other clinically meaningful outcomes including chronic lung disease and long term growth, neurodevelopment, lung or visual function were not reported in any of the available trials. REVIEWER'S CONCLUSIONS: The results of this meta-analysis confirm the commonly held view of today's clinicians that a policy of unrestricted, unmonitored oxygen therapy has potential harms, without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.

Humans↗

Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia.

OBJECTIVES: To assess the benefits and harm of administering anticonvulsants to infants of 37 weeks gestation or more following perinatal asphyxia with the primary aims of prevention of death or subsequent severe neurodevelopmental disability and/or the prevention of seizures. SEARCH STRATEGY: Relevant randomised controlled trials were identified using a combination of electronic database searches (MEDLINE), hand searches and a search of the Neonatal Review Group trials register. SELECTION CRITERIA: All randomised, or quasi-randomised, controlled clinical trials with reported data comparing the following outcomes: mortality, neurodevelopmental disability, neonatal seizures and adverse events, following anticonvulsant therapy in term infants (37 weeks or more), compared to controls with or without placebo, following perinatal asphyxia. DATA COLLECTION AND ANALYSIS: Methodological quality and validity of studies were assessed without consideration of the results. Data relevant to the outcome were extracted and analysed. MAIN RESULTS: Five randomised or quasi-randomised controlled trials which met the selection criteria were identified. No studies were of sufficient methodological quality and size to demonstrate a valid, clinically significant change in the risk of mortality or severe neurodevelopmental disability. A meta-analysis combining three studies comparing barbiturates with conventional therapy following perinatal asphyxia demonstrated no difference in risks of death, severe neurodevelopmental disability, or death or severe neurodevelopmental disability. REVIEWER'S CONCLUSIONS: At the present time, anticonvulsant therapy to term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice, other than in the treatment of prolonged or frequent clinical seizures. Any future studies should be of high quality: randomised control trials with allocation concealment, performance and outcome assessment blinding. Such studies should be of sufficient size, with minimal attrition, to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability, as the primary outcome measures.

Anticonvulsants↗

Minor depression in family practice: functional morbidity, co-morbidity, service utilization and outcomes.

BACKGROUND: Minor depression is a disabling condition commonly seen in primary care settings. Although considerable impairment is associated with minor depression, little is known about the course of the illness. Using a variety of clinical and functional measurements, this paper profiles the course of minor depression over a 1 year interval among a cohort of primary care patients. METHOD: Patients at a university-based primary care facility were screened for potential cases of depression and selected into three diagnostic categories: an asymptomatic control group; patients with a diagnosis of major depression; and, a third category, defined as minor depression, consisting of patients who reported between two and four symptoms of depression, but who failed to qualify for a diagnosis of major depression. Functional status, service use, and physical, social and mental health were assessed at baseline and at 3-month intervals for the ensuing year. RESULTS: Respondents with a baseline diagnosis of minor depression exhibited marked impairment on most measures both at baseline and over the following four waves. Their responses in most respects were similar to, although not as severe as, those of respondents with a baseline diagnosis of major depression. Both groups were considerably more impaired than asymptomatic controls. CONCLUSIONS: Minor depression is a persistently disabling condition often seen in primary care settings. Although quantitatively less severe than major depression, it is qualitatively similar and requires careful assessment and close monitoring over the course of the illness.

Adolescent↗

Studies of respiratory morbidity in rubber workers. Part III. Respiratory morbidity in processing workers.

Respiratory questionnaires and pulmonary function tests were administered to sixty-five men exposed to dust in the processing are from three rubber tire manufacturing plants. Similar tests were done on 189 "control" workers. Compared with the controls, the processing workers had a higher prevalence of chronic productive cough. Overall, the processing group showed a decrease in the ratio of FEV to FVC. The processing workers with more than ten years of exposure showed a significant decrease in the ratio of FEV1.0/FVC, the FEV1.0, the residual FEV1.0, and the flow rates at 50% and 25% of the forced vital capacity. None of the pulmonary function effects could be solely explained on the basis of smoking, age, ethnic, or socioeconomic factors: all were related to the length of exposure. Based on these results we conclude that exposure in the processing area produces pulmonary disease.

Adult↗

Psychiatric morbidity in primary public health care: a Nordic multicentre investigation. Part I: method and prevalence of psychiatric morbidity.

The prevalence of mental illness in five different Scandinavian primary care populations was investigated in this study. Patients consecutively consulting their general practitioner a particular week-day were included in the study. Initially the SCL-25 was applied and next the high scores and a sample of the low scores were interviewed by the PSE. In the analysis the screening procedure was first validated. The internal validity of the SCL was tested by means of Rasch latent structure analysis and the external validity tested by ROC/QROC analysis. Based on this, a short 8-item version of the SCL was developed. The prevalence of mental illness in all centres was 0.26 with a minimum of 0.14 in Nacka and a maximum of 0.34 in Turku.

Adolescent↗

Psychic vulnerability as a sequel to perinatal morbidity. A longitudinal twin study with special reference to psychiatric morbidity and inter-twin dependency.

In this follow-up study 497 twins from 335 twin deliveries were examined between the ages of 12-20 years to ascertain late effects of perinatal complications and mild neurological abnormalities on mental health, by means of questionnaires filled in by the parents and by the twins themselves. One third of the twins had not suffered from any perinatal complications, while one third had been small for gestational age, one third had been born prematurely and one third had suffered from respiratory disorders. Neonatal hypoglycaemia had been found in 22% and hyperbilirubinaemia in 7% of the twins. Perinatal complications had occurred in almost all those twins who later underwent inpatient psychiatric treatment. Most perinatal problems were reflected in the twin's dependency on his co-twin, showing in particular a cumulative effect when occurring simultaneously. Those twins who are currently more dependent learned to walk and speak later than the non-dependent ones, and their EEG background activity of ten years ago, at the age of 2-10 years, was more abnormal than that of the non-dependent ones, indicating brain organic, i.e. probably perceptual, factors enhancing the development of inter-twin dependency. The dependent twins were more submissive and had the most frequent feelings of inferiority. The neurological, psychological and family interactional factors that cause a twin to distrust himself and depend on his co-twin are also discussed in this study.

Dependency, Psychological↗