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PubMed1997

Infant arousals during mother-infant bed sharing: implications for infant sleep and sudden infant death syndrome research.

OBJECTIVE: Normative values for infant sleep architecture have been established exclusively in the solitary sleeping environment. However, most of the world's cultures practice some form of parent-infant cosleeping. In addition, no previous polysomnographic studies in infants examined the frequency of electroencephalogram (EEG) arousals. This is the first study to assess (a) EEG arousals in infants and their relationship to sleep stages; (b) the impact on arousals of mother-infant bed sharing; and (c) the temporal overlap of infant with maternal arousals during bed sharing. METHODOLOGY: Three nights of polysomnography were performed in 35 breastfeeding mother-infant pairs when the infants were 11 to 15 weeks old. An adaptation night was followed by one bed sharing night and one solitary sleeping night. Twenty infants had been bed sharing since birth and 15 were routine solitary sleepers. Both epochal awakenings (EWs), based on 30-second epoch scoring of sleep-wake stages, and more transient arousals (TAs) >/=3 seconds were quantified. RESULTS: Stage 3-4 sleep was associated with a striking paucity of EWs and TAs compared with stages 1-2 or rapid eye movement sleep. Bed sharing facilitated EWs and TAs selectively during stage 3-4 sleep. EWs from stage 3-4 sleep were more frequent on the bed sharing night than on the solitary night in both infant groups. Routinely bed sharing infants also exhibited more frequent TAs in stage 3-4 than the routine solitary sleepers in both conditions. In both groups, the number of infant arousals (EWs + TAs) that overlapped the mother's was doubled during bed sharing, with infant arousals leading most often. CONCLUSIONS: Mother-infant bed sharing promotes infant arousals. Together with a previous report that bed sharing reduces stage 3-4 sleep, this suggests that normative values for infant sleep must be interpreted within the context of the sleeping environment in which they were established. Given that arousability is diminished in stage 3-4, we speculate that, under otherwise safe conditions, the observed changes in stage 3-4 sleep and arousals associated with bed sharing might be protective to infants at risk for SIDS because of a hypothesized arousal deficit. The responsivity of the mother to infant arousals during bed sharing might also be protective.

Analysis of Variance↗
PubMed1990

Infant stimulation curriculum for infants with cerebral palsy: effects on infant temperament, parent-infant interaction, and home environment.

To assess the effects of intervention in cerebral palsy, 48 infants 12 to 19 months of age, with mild to severe spastic diplegia, were randomly assigned to receive either 6 months of infant stimulation followed by 6 months of physical therapy (test group) or 12 months of neurodevelopmental physical therapy (contrast group). The infant stimulation protocol consisted of cognitive, motor, sensory, and language activities. Outcome was assessed after 12 months by using Carey Infant Temperament Questionnaire subscores (activity, rhythmicity, adaptability, approach, threshold, intensity, mood, distractibility, and persistence); Roth Mother-Child Relationship Evaluation subscores (acceptance, overprotection, overindulgence, rejection); and Home Observation for Measurement of the Environment subscores (maternal responsiveness, avoidance of restriction and punishment, organization of environment, play materials, maternal involvement, and variety of daily stimulation). Motor and cognitive outcomes suggesting advantage for the test group have been reported previously. After 12 months of intervention, mothers with infants in the contrast group showed a greater improvement in emotional and verbal responsiveness as measured by the Home Observation for Measurement of the Environment (mean score change in control group = 1.2, test group = 0.3 P less than .04). None of the 19 other measures differed significantly between treatment groups in change from baseline. This study demonstrates no short-term systematic effect on temperament, maternal-infant interaction, or home environment attributable to the inclusion of an infant stimulation curriculum in an intervention program for infants with spastic diplegia. It suggests that motor and cognitive advantages associated with infant stimulation are not mediated by measurable changes in the psychosocial variables studied.

Cerebral Palsy↗
PubMed1987

Postnatal changes in colloid osmotic pressure in premature infants: in healthy infants, in infants with respiratory distress syndrome, and in infants born to mothers with premature rupture of membranes.

Colloid osmotic pressure (COP) of blood plasma during the first 4 days of life was measured in 63 neonates: 16 healthy preterm infants, 36 infants with respiratory distress syndrome (RDS), and 11 infants born to mothers with premature rupture of membranes. The relation between COP and total protein content of blood was significant in all groups over times from 1-3 h to 96 h. COP rose significantly by the age of 3 h compared to COP of umbilical cord plasma in all groups investigated. Infants with RDS showed a significant increase in COP during the investigation period. In healthy preterm infants the increase was less significant. In infants with RDS there was a negative correlation between changes in COP and body weight not seen in the other groups investigated. COP in neonates seems to reflect the compartmentation between vascular and interstitial spaces. Measurement of COP could be clinically useful in assessing hemodynamic adaptation after birth and also in assessing edema formation and water balance in infants with RDS.

Birth Weight↗
PubMed1986

[Body movements during sleep in the infant: comparison between control infants and siblings of infants dying of sudden infant death syndrome].

Day-sleep polygraphic recordings were performed in 10 normal infants and 10 siblings of infants who died of sudden infant death syndrome. Body movements were studied in both groups of infants during 3 stages of sleep. In controls and siblings, the mean number of body movements per sleep hour, per infant was respectively 7 or 6 in quiet sleep and 22 and 23 in REM sleep; the mean duration of body movement was longer (11.3 sec) in REM sleep than in non-REM sleep (9.4 sec). In both cases, there was no significant difference between the 2 groups. An analysis of the movement duration showed that most of them lasted between 5 and 10 sec and in siblings were statistically more numerous during indeterminate sleep. In both groups, these movements appeared more often at the beginning and at the end of the quiet sleep, but were more equally distributed in the REM sleep. Respectively 15 and 13.7% of these movements in the normal and sibling group were accompanied by a brief respiratory pause. The relation between body movements and sleep is discussed.

Humans↗
PubMed2000

Changing concepts of sudden infant death syndrome: implications for infant sleeping environment and sleep position. American Academy of Pediatrics. Task Force on Infant Sleep Position and Sudden Infant Death Syndrome.

The American Academy of Pediatrics has recommended since 1992 that infants be placed to sleep on their backs to reduce the risk of sudden infant death syndrome (SIDS). Since that time, the frequency of prone sleeping has decreased from >70% to approximately 20% of US infants, and the SIDS rate has decreased by >40%. However, SIDS remains the highest cause of infant death beyond the neonatal period, and there are still several potentially modifiable risk factors. Although some of these factors have been known for many years (eg, maternal smoking), the importance of other hazards, such as soft bedding and covered airways, has been demonstrated only recently. The present statement is intended to review the evidence about prone sleeping and other risk factors and to make recommendations about strategies that may be effective for further reducing the risk of SIDS. This statement is intended to consolidate and supplant previous statements made by this Task Force.

Cause of Death↗
PubMed2000

Nitric oxide for respiratory failure in infants born at or near term.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To determine whether treatment of hypoxemic newborn infants with inhaled nitric oxide (INO) improves oxygenation and reduces the rates of death, or the requirement for ECMO. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. SELECTION CRITERIA: Randomized and quasi randomized studies in term and near term infants. Administration of inhaled nitric oxide. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. DATA COLLECTION AND ANALYSIS: Eight randomized controlled studies were found in term and near term infants with hypoxia. Entry criteria were reasonably consistent except for the one trial that studied only infants with congenital diaphragmatic hernia (Ninos 1997). MAIN RESULTS: Inhaled nitric oxide appears to improve outcome in hypoxemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. It does not appear to affect outcome whether infants have clear echocardiographic evidence of PPHN or not. The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened. REVIEWER'S CONCLUSIONS: On the evidence presently available, it appears reasonable to use inhaled nitric oxide in a concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia. Longterm neurodevelopmental and pulmonary followup of surviving infants enrolled in randomized trials of INO are required to establish more firmly the role of INO in the treatment of neonatal respiratory failure.

Fetal Hypoxia↗
PubMed2000

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To determine whether, in preterm newborn infants who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation and reduces the rates of death, or adverse neurodevelopmental outcome. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. SELECTION CRITERIA: Randomized and quasi randomized studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide. Clinically relevant outcomes, including death, oxygenation, intraventricular haemorrhage. DATA COLLECTION AND ANALYSIS: One randomized controlled trial of nitric oxide therapy was found in preterm infants with a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). MAIN RESULTS: No significant effect of inhaled nitric oxide on any outcome variable was found. In particular there was no effect on the primary outcome variable of death or bronchopulmonary dysplasia. REVIEWER'S CONCLUSIONS: There is currently no published information to support the use of inhaled nitric oxide in preterm infants. Preterm infants should not be treated with inhaled nitric oxide except in the context of prospective, randomized controlled trials.

Administration, Inhalation↗
PubMed2000

Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review was to assess the risks and benefits of administration of a diuretic acting on the loop of Henle (loop diuretic) in preterm infants with or developing chronic lung disease (CLD). Primary objectives were to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives were to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least 5 days of age were all randomly allocated to receive a loop diuretic either enterally or intravenously. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included toxicity and pulmonary mechanics (e.g., lung compliance and airway resistance). DATA COLLECTION AND ANALYSIS: 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, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: The only loop diuretic used in the studies which met the selection criteria was furosemide. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants < 3 weeks of age developing CLD, furosemide administration has either inconsistent effects or no detectable effect. In infants > 3 weeks of age with CLD, a single intravenous dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for 1 hour. Chronic administration of furosemide improves both oxygenation and lung compliance. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of furosemide improve lung compliance. Chronic administration of intravenous or enteral furosemide improves oxygenation. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of systemic loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. Randomized trials are needed to assess the effects of furosemide administration on survival, duration of ventilatory support and oxygen administration, length of hospital stay, potential complications and long-term outcome.

Chronic Disease↗
PubMed2000

Nebulized racemic epinephrine for extubation of newborn infants.

BACKGROUND: Following a period of mechanical ventilation, post-extubation upper airway obstruction can occur in newborn infants, especially after prolonged, traumatic or multiple intubations. The subsequent increase in upper airway resistance may lead to respiratory insufficiency and failure of extubation. The vasoconstrictive properties of epinephrine, and its proven efficacy in the treatment of croup in infants, has led to the routine use of inhaled nebulised epinephrine immediately post-extubation in some neonatal units. It is also recommended for neonates with post-extubation tracheal obstruction and stridor in neonatal and respiratory textbooks and reviews. OBJECTIVES: The primary objective was to assess whether nebulised epinephrine administered immediately after extubation in neonates weaned from IPPV decreases the need for subsequent additional respiratory support. SEARCH STRATEGY: Searches were made of Medline (MeSH search terms 'epinephrine' and 'exp infant, newborn'), the Oxford Database of Perinatal trials, expert informants and journal hand searching mainly in the English language, expert informant searches in the Japanese language by Prof. Ogawa, previous reviews including cross references, abstracts, and conference and symposia proceedings. SELECTION CRITERIA: All randomised and quasi-randomised control trials in which nebulised epinephrine was compared with placebo immediately post-extubation in newborn infants who have been weaned from IPPV and extubated, with regard to clinically important outcomes (i.e. need for additional respiratory support, increase in oxygen requirement, respiratory distress, stridor or the occurrence of side effects). DATA COLLECTION AND ANALYSIS: No studies met our criteria for inclusion in this review. MAIN RESULTS: No studies were identified which looked at the effect of inhaled nebulised epinephrine on clinically important outcomes in infants being extubated. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: There is no evidence either supporting or refuting the use of inhaled nebulised racemic epinephrine in newborn infants. IMPLICATIONS FOR RESEARCH: randomised controlled trials are needed comparing inhaled nebulised racemic epinephrine with placebo in neonates post-extubation. This should be looked at both as a routine treatment post-extubation and as specific treatment for post-extubation upper airway obstruction. Study populations should include the group of infants at highest risk for upper airway obstruction from mucosal swelling because of their small glottic and sub-glottic diameters (ie those infants with birthweights less than 1000 grams).

Administration, Inhalation↗
PubMed2000

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: 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, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Chronic Disease↗
PubMed2000

Maternal and infant factors predicting disease progression in human immunodeficiency virus type 1-infected infants. Women and Infants Transmission Study Group.

BACKGROUND: Infants with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection have widely variable courses. Previous studies showed that a number of maternal and infant factors, when analyzed separately, are associated with infant HIV-1 disease progression. In this study, clincal, virologic, and immunologic characteristics in the mothers and infants were examined together to determine the predictors of disease progression by 18 months of age and the associations with rapid progression during the first 6 months of life. METHODS: One hundred twenty-two HIV-1-infected women whose infants were HIV-1 infected were identified from the Women and Infants Transmission Study (WITS) cohort. WITS is a longitudinal natural history study of perinatal HIV-1 infection carried out in 6 sites in the continental United States and in Puerto Rico. The women were enrolled during pregnancy and their infants were enrolled at the time of delivery and followed prospectively by a standardized protocol. Virologic and immunologic studies were performed in laboratories certified by National Institutes of Health-sponsored quality assurance programs. Maternal factors in pregnancy were used as potential predictors of infant disease progression (progression to Centers for Disease Control and Prevention [CDC] Clinical Class C disease or death by 18 months of age) or as correlates of progression at <6 months of age. Infant factors defined during the first 6 months of life were used as potential predictors of progression during 6 to 18 months of age and as correlates of progression at <6 months of age. RESULTS: Progression by 18 months of age occurred in 32% of infants and by 6 months of age in 15%. Maternal characteristics that, by univariate analysis, were significant predictors of infant disease progression by 18 months of age were elevated viral load, depressed CD4(+)%, and depressed vitamin A. CD8(+)%, CD8(+) activation markers, zidovudine (ZDV) use, hard drug use, and gestational age at delivery were not. When examined in a combined multivariate analysis of maternal characteristics, only vitamin A concentration independently predicted infant progression. Infant characteristics during the first 6 months of life that, by univariate analysis, were associated with disease progression included elevated mean viral load at 1 to 6 months of age, depressed CD4(+)%, CDC Clinical Disease Category B, and growth delay. Early HIV-1 culture positivity (<48 hours), CD8(+)%, CD8(+) activation markers, and ZDV use during the first month of life did not predict progression. Multivariate analysis of infant characteristics showed that the only independent predictors were progression to CDC Category B by 6 months of age (odds ratio [OR], 5.80) and mean viral load from 1 to 6 months of age (OR, 1.99). The final combined maternal and infant analysis included the significant maternal and infant characteristics in a multivariate analysis. It showed that factors independently predicting infant progression by 18 months of age were progression to CDC Category B by 6 months of age (OR, 5.80) and elevated mean HIV-1 RNA copy number at 1 to 6 months of age (OR, 1.99). The characteristics associated with rapid progression to CDC Category C disease or death by 6 months of age were also examined. The only maternal characteristic associated with progression by 6 months in multivariate analysis was low maternal CD4(+)%. The infant characteristics associated with progression by 6 months of age in multivariate analysis were depressed mean CD4(+)% from birth through 2 months and the presence of lymphadenopathy, hepatomegaly, or splenomegaly by 3 months. Infant ZDV use was not assocciated with rapid progression. CONCLUSION: The strongest predictors of progression by 18 months are the presence of moderate clinical symptoms and elevated RNA copy number in the infants in the first 6 months of life. In contrast, progression by 6 months is associated with maternal and infant immun

Analysis of Variance↗
PubMed2000

Continuous distending airway pressure for respiratory distress syndrome in preterm infants.

BACKGROUND: Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants (Greenough 1998, Bancalari 1992). Intermittent positive pressure ventilation (IPPV) with surfactant is the standard treatment for the condition. The major difficulty with IPPV is that it is invasive, resulting in airway and lung injury and contributing to the development of chronic lung disease. OBJECTIVES: In spontaneously breathing preterm infants with RDS, to determine if continuous distending airway pressure (CDAP) reduces the need for IPPV and associated morbidity without adverse effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal hand searching mainly in the English language. SELECTION CRITERIA: All trials using random or quasi-random patient allocation of newborn infants with RDS were eligible. Interventions were continuous distending airway pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharnygeal tube, or endotracheal tube, or continuous negative pressure (CNDP) via a chamber enclosing the thorax and lower body, compared with standard care. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each author, were used. MAIN RESULTS: CDAP is associated with a lower rate of failed treatment (death or use of assisted ventilation), overall mortality, and mortality in infants with birthweights above 1500 g. The use of CDAP is associated with an increased rate of pneumothorax. REVIEWER'S CONCLUSIONS: In preterm infants with RDS the application of CDAP either as CPAP or CNDP is associated with some benefits, particularly in infants with birthweights over 1500 gms. The extent of this benefit is difficult to assess given the outdated methods to administer CDAP, low use of antenatal corticosteroids, non-availability of surfactant and the intensive care setting of the 1970's in which these trials were done. Where resources are limited, such as in developing countries, CPAP for RDS may have a clinical role. Further research is required to determine the best mode of administration and its role in modern intensive care settings

Humans↗
PubMed2000

Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants.

BACKGROUND: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 seconds. This has been shown to result in less lung injury in experimental studies. OBJECTIVES: The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease (CLD) without adverse effects. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching by the Cochrane Collaboration, mainly in the English language. Expert informant's search in the Japanese language was made by Prof. Y. Ogawa. SELECTION CRITERIA: Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life. DATA COLLECTION AND ANALYSIS: The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. The standard method of the Cochrane Neonatal Review Group was used to synthesize the data using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. MAIN RESULTS: Meta-analysis of the six eligible studies comparing HFOV with CV revealed that there is no difference in mortality. There are trends toward decreases in CLD in survivors at 28-30 days, 'death or CLD at 28-30 days' and CLD in survivors at 36-37 weeks postmenstrual age or discharge in the HFOV group. However, there are trends towards increases in severe (grades 3 & 4) intraventricular hemorrhage (IVH) and in periventricular leukomalacia (PVL) in the HFOV group. HFOV results in a small increase in any air leak syndrome (ALS), [summary RR 1.20 (1.03, 1.39)]. Only 2 trials have included neurodevelopmental follow up and more survivors in the HFOV group are abnormal [summary RR 1.26 (1.01, 1.58)]. In the subgroup of four trials where a high volume strategy (HVS) was used, HFOV results in more favourable pulmonary outcomes. There are significantly lower rates of CLD in survivors at 28-30 days [summary RR 0.53 (0.36, 0.76)] and of 'death or CLD at 28-30 days' [summary RR 0.56 (0.40, 0.77) with a non-significant trend towards a reduction in oxygen use at 36-37 weeks postmenstrual age or discharge [summary RR 0.74 (0.55, 1.01)]. There were no differences in the rates of IVH or PVL. Of the four trials in the subgroup using surfactant routinely, three also used the HVS. The trends in results were similar with surfactant to those for the HVS subgroup analysis. One trial suggests that HFOV may reduce the cost of in-hospital care. In the subgroup of two trials (HIFI 1989, Rettwitz-Volk 1998) not using a HVS there is no effect of HFOV on the rate of CLD; however, there is an increase in the rate of PVL [summary RR 1.64 (1.02, 2.64). REVIEWER'S CONCLUSIONS: The overall meta-analyses is dominated by the large HIFI study which did not use the HVS recommended on the basis of animal studies, and in which surfactant was not available. Studies which used HVS have shown some benefits in short term measures of CLD without an in

High-Frequency Ventilation↗
PubMed2000

Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants.

BACKGROUND: Preterm infants being extubated following a period of intermittent positive pressure ventilation via an endotracheal tube are at risk of developing respiratory failure as a result of apnea, respiratory acidosis and hypoxia. Nasal continuous positive airway pressure appears to stabilise the upper airway, improve lung function and reduce apnea and may therefore have a role in facilitating extubation in this population. OBJECTIVES: In preterm infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV), does management with nasal continuous positive airways pressure (NCPAP) lead to an increased proportion remaining free of additional ventilatory support, compared to extubation directly to headbox oxygen? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline, previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language and expert informant searches in the Japanese language by Prof. Ogawa. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which NCPAP (delivered by any method) was compared with headbox oxygen for post-extubation care were included. Methodological quality was assessed independently by the two authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors. Prespecified subgroup analysis to determine the impact of different levels of NCPAP, differences in duration of IPPV and use of aminophylline were also performed using the same package. MAIN RESULTS: Nasal CPAP, when applied to preterm infants being extubated following IPPV, reduces the incidence of adverse clinical events (apnea, respiratory acidosis and increased oxygen requirements) indicating the need for additional ventilatory support. A reduction in the incidence of chronic lung disease at 28 days of age is also seen in the group extubated to NCPAP. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: nasal CPAP is effective in preventing failure of extubation and reducing oxygen use at 28 days of life in preterm infants following a period of endotracheal intubation and IPPV. Implication for research: further definition of the patient gestational age and weight groups in whom these results apply is required. Optimal levels of NCPAP as well as methods of administration remain to be determined.

Humans↗
PubMed2000

Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants.

BACKGROUND: Many preterm babies who survive, having had respiratory distress syndrome (RDS) or not, go on to develop chronic lung disease (CLD). This is probably due to persistence of inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established CLD. However it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES: To determine if late (> 3 weeks) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the treatment of chronic lung disease (CLD) in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment initiated at > 3 weeks of age in preterm infants with CLD were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality before discharge, failure to extubate, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding, bowel perforation, echodensities on ultrasound scan of brain, need for home oxygen, glycosuria, need for late rescue with dexamethasone, cerebral palsy in survivors and blindness in survivors were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Delayed steroid treatment had no effect on mortality. The only beneficial effects were reductions in failure to extubate by 7 or 28 days, need for late rescue treatment with dexamethasone, chronic lung disease at 36 weeks, and discharge to home on oxygen therapy. There was no increase in risk of infection, necrotising enterocolitis, or gastrointestinal bleeding. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no effect on blindness. There were increases in long-term neurologic sequelae including abnormal neurologic examination and cerebral palsy, the latter of borderline statistical significance. REVIEWER'S CONCLUSIONS: The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. There is a worrying increase in adverse neurological outcomes in infants treated with postnatal steroids (see also Review of Early Postnatal corticosteroids). Corticosteroids should be reserved for infants who cannot be weaned from mechanical ventilation. The dose of dexamethasone and the duration of any course of treatment should be minimised.

Anti-Inflammatory Agents↗
PubMed2000

Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants.

BACKGROUND: Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat CLD because of their potent anti-inflammatory effects. OBJECTIVES: To determine if postnatal corticosteroid treatment is of benefit in the prevention of chronic lung disease (CLD) in the preterm infant. This review examines the outcome of trials where preterm infants at risk of CLD were given postnatal steroids within 96 hours after birth. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Controlled Trials Register, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment within 96 hours of birth (early) in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, failure to extubate, pulmonary air leak, survival without chronic lung disease, CLD defined at 28 days postnatal age and 36 weeks post menstrual age, patent ductus arteriosus (PDA), severe intraventricular hemorrhage (IVH), infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding and longterm outcome were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Fifteen randomised controlled trials of early postnatal corticosteroid treatment of preterm babies at risk of developing CLD were identified. A meta-analysis of these trials demonstrates benefits as regards earlier extubation, decreased risks of CLD at both 28 days and 36 weeks, death or CLD at 28 days, and PDA. There was an almost significant reduction in the risk of pulmonary air leak and in death or CLD at 36 weeks in the babies treated with early corticosteroids. There were no differences in the rates of neonatal mortality, infection, severe ROP, severe IVH, NEC and pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects and the risks of hyperglycaemia and hypertension were also increased. Several adverse neurological effects were found at follow-up examinations of survivors treated with early steroids: abnormal neurological examination, cerebral palsy and developmental delay. REVIEWER'S CONCLUSIONS: The benefits of early postnatal corticosteroid treatment (< 96 hours) may not outweigh the known or potential adverse effects of this treatment. Gastrointestinal effects early in the neonatal period and neurological effects seen at follow-up mean that current use of early postnatal steroids needs to be reconsidered. There is a compelling need for the long term follow-up and reporting of late outcomes, especially neurologic and developmental outcomes, among surviving infants who participated in all randomized trials of early postnatal corticosteroid treatment. The role of inhaled steroids remains to be elucidated.

Anti-Inflammatory Agents↗
PubMed2000

Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

BACKGROUND: Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. OBJECTIVES: To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality up to 28 days and before discharge, failure to extubate, mortality and / or chronic lung disease at 28 days and 36 weeks, CLD at 28 days and 36 weeks, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), pneumothorax, necrotizing enterocolitis (NEC), gastrointestinal bleeding, severe intraventricular hemorrhage (IVH), hypertrophic cardiomyopathy, late rescue with dexamethasone and abnormal neurological examination at follow-up were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, and NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There was only one small study of longterm follow-up and it did not show any increase in adverse neurological outcome. REVIEWER'S CONCLUSIONS: Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. No reliable evidence concerning long term effects is provided by the trials included in this review. In view of the evidence of an important increase in cerebral palsy and other adverse neurodevelopmental outcomes from trials in which postnatal steroid was begun either earlier or later than 7-14 days, there are reasonable grounds for extending this concern to moderately early initiation of steroid therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed.

Anti-Inflammatory Agents↗
PubMed1993

Parent-infant cosleeping: the appropriate context for the study of infant sleep and implications for sudden infant death syndrome (SIDS) research.

Nearly all laboratory research on human infant sleep assumes that solitary sleeping is the normal and desirable environment. Yet solitary sleeping in infancy is a very recent custom limited to Western industrialized societies, and most of the world's people still practice parent-infant cosleeping. A hypothesis is presented that cosleeping provides a sensory-rich environment which is the more appropriate environment in which to study normal infant sleep. In addition, two preliminary, in-laboratory, polygraphic investigations of mother-infant cosleeping are reported in normal infants within the peak age range for sudden infant death syndrome (SIDS). Five mother-infant pairs coslept for 1 night in the first study; in the second, three additional pairs slept separately for 2 nights and coslept the third consecutive night. The results suggest that cosleeping is associated with enhanced infant arousals and striking temporal overlap in infant and maternal arousals. Infant sleep also showed subtle alterations with cosleeping, as manifested in increased overlap with corresponding maternal sleep stages and decreased amount of Stage 3-4. These are the first in-laboratory investigations of parent-infant cosleeping. The implications of the hypothesis and preliminary results for research on the normal development of infant sleep and on SIDS are discussed.

Adult↗