Biomedical subjects

D J Henderson-Smart

Publications and source records attributed to D J Henderson-Smart.

At least 19 recordsLinked to original sources

PubMed2001

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.

BACKGROUND: Mild-moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve outcome. OBJECTIVES: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy. SEARCH STRATEGY: Relevant trials were identified in the register of trials maintained by the Cochrane Pregnancy and Childbirth Group. In addition, the Cochrane Controlled Trial Register, MEDLINE, and EMBASE were searched. Date of last search: October 2000. SELECTION CRITERIA: All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy, defined whenever possible as systolic blood pressure 140-169 mmHg and diastolic blood pressure 90-109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. MAIN RESULTS: Overall, this review includes 40 studies (3797 women), 24 of which compared an antihypertensive drug with placebo/no antihypertensive drug (2815 women). There is a halving in the risk of developing severe hypertension associated with the use of antihypertensive drug(s) [17 trials, 2155 women; relative risk (RR) 0.52 (95% confidence interval (CI) 0.41 to 0.64); risk difference (RD) -0.09 (-0.12 to -0.06); number needed to treat (NNT) 12 (9 to 17)] but little evidence of a difference in the risk of pre-eclampsia [19 trials, 2402 women; RR 0.99 (0.84 to 1.18)]. Similarly, there is no clear effect on the risk of the baby dying [23 trials, 2727 women; RR 0.71(0.46 to 1.09)], preterm birth [12 trials, 1738 women; RR 0.98 (0.85 to 1.13)], or small for gestational age babies [17 trials, 2159 women; RR 1.13 (0.91 to 1.42)]. There were no clear differences in any other outcomes. Seventeen trials (1182 women) compared one antihypertensive drug with another. There is no clear difference between any of these drugs in the risk of developing severe hypertension, and proteinuria/pre-eclampsia. Other antihypertensive agents seem better than methyldopa for reducing the risk of the baby dying [14 trials, 1010 subjects, RR 0.49 (0.24 to 0.99); RD -0.02 (-0.04 to 0.00); NNT 45 (22 to 1341)]. Other outcomes were only reported by a small proportion of studies, and there were no clear differences. REVIEWER'S CONCLUSIONS: It remains unclear whether antihypertensive drug therapy for mild-moderate hypertension during pregnancy is worthwhile.

Antihypertensive Agents↗

PubMed2001

Rescue high frequency oscillatory ventilation vs conventional ventilation for infants with severe pulmonary dysfunction born at or near term.

BACKGROUND: Pulmonary disease is a major cause of mortality and morbidity in term and near term infants. Conventional ventilation (CV) has been used for many years but may lead to lung injury, require the subsequent use of more invasive treatment such as extra corporeal membrane oxygenation (ECMO), or result in death. There are some studies indicating that high frequency oscillatory ventilation (HFOV) may be more effective in these infants as compared to CV. OBJECTIVES: The objective of this review is to determine if HFOV, as compared to conventional ventilation, reduces mortality and morbidity in term or near term infants with intractable lung disease without an increase in adverse effects. SEARCH STRATEGY: Standard search methods of the Cochrane Neonatal Review group were used. These included searches of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, and journal hand searching by the Cochrane Collaboration. SELECTION CRITERIA: Randomized or quasi-randomized trials comparing HFOV and CV in term or near term infants with intractable respiratory failure were included in this review. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group were used. The investigators separately extracted, assessed and coded all data for each study. Any disagreement was resolved by discussion. Data were synthesized using relative risk (RR) and risk difference (RD). MAIN RESULTS: Only one trial met the inclusion criteria. This rescue trial of 81 infants showed no evidence of a reduction in mortality at 28 days [RR 0.51 (0.05, 5.43)] or in failed therapy on the assigned mode of ventilation requiring cross-over to the other mode [RR 0.73 (0.47, 1.13)]. There were no significant differences in the numbers of patients requiring extracorporeal membrane oxygenation [RR 2.05 (0.85, 4.92)], days on a ventilator, days in oxygen or days in hospital. REVIEWER'S CONCLUSIONS: There are no data from randomized controlled trials supporting the routine use of rescue HFOV in term or near term infants with severe pulmonary dysfunction. The area is complicated by diverse pathology in such infants and by the occurrence of other interventions (surfactant, inhaled nitric oxide, inotropes). Randomized controlled trials are needed to establish the role of rescue HFOV in near term and term infants with pulmonary dysfunction before widespread use of this mode of ventilation in such infants.

High-Frequency Ventilation↗

PubMed2001

Do very sick neonates born at term have antenatal risks? 1. Infants ventilated primarily for problems of adaptation to extra-uterine life.

AIMS: 1. Ascertain antenatal and intrapartum risk factors for term neonates ventilated primarily for 'perinatal asphyxia'. 2. Describe the neonatal morbidity and mortality. METHODS: Population-based case control cohort study. SETTING: Sydney and four large rural/urban health areas in New South Wales. SUBJECTS: Singleton term infants, no major congenital anomaly: subset of 83 infants ventilated primarily for 'asphyxia' from 182 cases admitted to a tertiary neonatal intensive care unit (NICU) for mechanical ventilation, 550 randomly selected controls. Outcome. Risk factors for case status by maternal, antenatal, labor, delivery, and combined epochs, adjusted odds ratios (OR), 95 per cent confidence intervals (CI), p < 0.05. RESULTS: Predictors of case status by multivariate epochs: Primigravida (1.8 [1.1, 2.8]), thyroid disease (7.8 [1.1, 57.0]), any antenatal complication (5.1 [3.0, 8.6]), growth restriction (4.2 [1.7, 10.4]), male gender (2.1 [1.3, 3.5]), gestational age >40 weeks (1.9 (1.1, 3.3)), prolonged rupture of membranes (9.7 [1.3, 72.5]), complicated labor (6.6 [3.7, 11.9]), induced labor (2.2 [1.3, 3.9]), prostaglandins 2.46 [1.23, 4.91]), maternal pyrexia (10.8 [2.8, 42.7]), placental hemorrhage in labor (OR 4.24 [1.45, 12.42]), forceps delivery (4.1 [1.9, 8.5]), emergency cesarean section (4.7 [2.6, 8.7]). Twenty case infants (24%) and no control infants died. CONCLUSIONS: This study has shown maternal and antepartum risk factors for severe neonatal morbidity in term infants. More centers need to become interested in the term baby, so that a larger multicenter study can further elucidate the heterogeneous causal pathways to term neonatal morbidity.

Adaptation, Biological↗

PubMed2001

Do very sick neonates born at term have antenatal risks? 2. Infants ventilated primarily for lung disease.

AIMS: 1. Ascertain antenatal and intrapartum risk factors for term neonates ventilated primarily for respiratory problems. 2. Describe the neonatal morbidity and mortality. METHODS: Population-based case control cohort study. SETTING: Sydney and four large rural/urban Health Areas in New South Wales, 1996. SUBJECTS: Singleton term infants, no major congenital anomaly: subset of 99 infants ventilated primarily for respiratory problems from 182 cases admitted to a tertiary neonatal intensive care unit (NICU) for mechanical ventilation, and 550 randomly selected controls. OUTCOME: Risk factors for case status by maternal, antenatal, labor, delivery, and combined epochs, adjusted Odds Ratios (OR), 95 per cent Confidence Intervals (CI), p<0.05. RESULTS: Predictors of case status by multivariate epochs: mother's age > or =35 years (1.9 (1.1, 3.2) p=0.03), primigravida (1.8 (1.1, 2.8) p=0.01), any antenatal complication (3.8 (2.4, 5.9) p=0.0001), birth weight < 3rd percentile (3.7 (1.5, 9.1) p=0.006), gestational diabetes (2.9 (1.3, 6.9) p=0.01), maternal pyrexia (6.5 (1.6, 27.2) p=0.01), birth weight >90th percentile (1.8 (1.01, 3.2) p=0.047), gestation 37-38 weeks (2.3 (1.5, 3.6) p=0.0004), forceps (4.4 (2.1, 9.1) p=0.0001), elective cesarean section (3.7 (2.0, 6.5) p=0.0001), emergency cesarean section (4.5 (2.4, 8.4) p=0.0001). Case mortality rate was 5 per cent. CONCLUSION: The pathways to neonatal respiratory morbidity in term infants are multifactorial. Several areas which warrant more in-depth study are: elective cesarean section at 37-38 weeks gestation, fetal growth restriction, macrosomia and the pattern of in-utero growth, maternal weight gain during pregnancy, gestational diabetes, pyrexia in labor and the role of chorioamnionitis.

Adult↗

PubMed2000

Anticonvulsants for women with pre-eclampsia.

BACKGROUND: Pre-eclampsia is a relatively common complication of pregnancy. Anticonvulsants are used in the belief they help prevent eclamptic fits and subsequent poor outcomes for mother and infant. OBJECTIVES: The objective of this review was to assess the effects of anticonvulsants for women with pre-eclampsia on the women and their children. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, and the Cochrane Controlled Trials Register, 1999 Issue 3. SELECTION CRITERIA: Randomised trials comparing anticonvulsants with placebo or no anticonvulsants or comparisons of different anticonvulsants in women with pre-eclampsia. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Nine studies were included. Comparing magnesium sulphate with placebo/no anticonvulsant the relative risk (RR) of eclampsia was 0.33, 95% confidence interval (CI) 0.11 to 1.02. There was no significant difference detected in the risk of caesarean section (RR 1.04, 95% CI 0.92 to 1.17). Magnesium sulphate appeared to be better than phenytoin at reducing the risk of eclampsia (RR 0.05, 95% CI 0.00 to 0.84). However there was an increased risk of caesarean section with magnesium sulphate compared to phenytoin (RR 1.21, 95% CI 1.05 to 1. 41). No statistically significant differences were reported for any other clinically important outcomes. Studies comparing magnesium sulphate and diazepam were too small for any reliable conclusions. REVIEWER'S CONCLUSIONS: There is not enough evidence to establish the benefits and hazards of anticonvulsants for women with pre-eclampsia. If an anticonvulsant is used, magnesium sulphate appears to be the best choice.

Anticonvulsants↗

PubMed2000

Postoperative caffeine for preventing apnea in preterm infants.

BACKGROUND: Growing ex-preterm infants who undergo general anesthesia for surgery at about term-equivalent age may have episodes of apnea, cyanosis and bradycardia during the early postoperative period. Caffeine treatment given at the time of operation might prevent these episodes. OBJECTIVES: In ex-preterm infants who undergo general anesthesia for surgery, does the prophylactic use of caffeine prevent episodes of apnea, cyanosis and bradycardia during the postoperative period without clinically important side effects? SEARCH STRATEGY: The standard strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, Medline, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which treatment was compared with placebo or no treatment, were included. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, evaluate quality and to extract data. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institution(s). Each author extracted data separately, compared and resolved differences. Meta-analysis used relative risk and risk difference. MAIN RESULTS: In each trial apnea/bradycardia occurred in fewer treated than control infants. In two trials (Welborn 1989, LeBard 1989) continuous recordings of oxygen saturation detected hypoxaemic episodes (<90 %) in fewer treatment than control infants. No infant in any trial required intubation and mechanical ventilation. No adverse effects were reported. REVIEWER'S CONCLUSIONS: Implications for practice. Caffeine can be used to prevent postoperative apnea/bradycardia and episodes of oxygen desaturation in growing preterm infants if this is deemed clinically necessary. In view of the small numbers of infants studied in these trials and uncertainty concerning the clinical significance of the episodes, caution is warranted in applying these results to routine clinical practice. Implications for research. There is a need to determine which infants might benefit most by this treatment. Studies confined to those most at risk of apnea (prior history, younger postmenstrual age) and those that might require mechanical ventilation (chronic lung disease) would be of value.

Anesthesia, General↗

PubMed2000

Doxapram treatment for apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram has been used to stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In preterm infants with recurrent apnea, does treatment with doxapram lead to a clinically important reduction in apnea and use of Intermittent positive airways pressure (IPPV), without clinically important side effects? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, the Cochrane Collaboration Clinical Trials Register, MEDLINE (using text words 'doxapram', 'apnea or apnoea' and Mesh term 'infant, premature') previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof. Y. Ogawa in 1996. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included. DATA COLLECTION AND ANALYSIS: Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out. MAIN RESULTS: Only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo, was found. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm. REVIEWER'S CONCLUSIONS: Although intravenous doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No longterm outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice.

Apnea↗

PubMed2000

Doxapram versus methylxanthine for apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram and methylxanthine drugs have been used to stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In preterm infants with recurrent apnea, how does treatment with doxapram compare with treatment with theophylline in leading to a clinically important reduction in apnea and use of mechanical ventilation, without clinically important side effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group, as outlined in the Cochrane Library, was used. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which doxapram was compared with methylxanthine (e.g. theophylline) for the treatment of apnea, were eligible. There must have been an effort to exclude specific causes of apnea. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, assess quality and to extract and synthesize data. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institution(s). Additional information was requested from authors to clarify methodology. Each author extracted the data separately, then they were compared and differences resolved. Meta-analysis was carried out with use of relative risk and risk difference. MAIN RESULTS: In these trials involving a relatively small number of preterm infants with apnea of prematurity, there is no apparent difference between the effect of intravenous treatment with doxapram or methylxanthine on the incidence of apnea within 48 hours. There were no infants reported to have been given mechanical ventilation on either treatment. No adverse effects were reported. REVIEWER'S CONCLUSIONS: Implications for practice. The overall results of these small trials suggest that intravenous doxapram and intravenous methylxanthine are not different in their effectiveness in the short term in the treatment of apnea of prematurity. Caution is warranted as the number of patients in these trials is too small to exclude an important difference between these two treatments or to exclude the possibility of less common side effects. Longer term outcome of infants treated in these trials has not been reported. Implications for research. Further studies would require a large number of infants, stratified by gestation, to clarify which infants are likely to benefit and whether there might be differences in responses or side effects with these two drugs at different ages. It would be valuable to include important clinical outcomes such as use of mechanical ventilation as well as subsequent growth and development in future studies. Responses to treatment would have to take account of co-interventions, such as nasal continuous airway pressure which is frequently used post-intubation.

Aminophylline↗

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

Prophylactic methylxanthine for extubation in preterm infants.

BACKGROUND: When preterm infants have been given intermittent positive pressure ventilation (IPPV) for respiratory failure, weaning from support and tracheal extubation may be difficult. A significant contributing factor is thought to be the relatively poor respiratory drive and tendency to develop hypercarbia and apnea, particularly in very preterm infants. Methylxanthine treatment started before extubation might stimulate breathing and increase the chances of successful weaning from IPPV. OBJECTIVES: Main question: in preterm infants being weaned from IPPV and in whom endotracheal extubation is planned, does treatment with methylxanthine reduce the use of intubation and IPPV, without clinically important side effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group, as outlined in the Cochrane Library, was used. SELECTION CRITERIA: All published trials utilising random or quasi-random patient allocation, in which treatment with methylxanthine (theophylline or caffeine) was compared with placebo or no treatment to improve the chances of successful extubation of preterm or low birth weight infants, were included. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The second author assessed the quality of trials blinded to the authors and extracted data independently. Relative risk and risk difference was used in the meta-analysis. MAIN RESULTS: Overall analysis of the 4 published trials suggests that methylxanthine treatment results in a reduction in the use of mechanical ventilation. Three of the 4 studies are consistent with this overall result while one small trial (Barrington 1993) found no benefit. One study (Durand 1987) found that treatment was effective in those born at less than 1000 grams and who were less than one week old. In the small prespecified subgroups in this trial, infants of less than 1 kg birth weight and older than one week and those of birth weight 1000-1250 grams who had failed extubation once, no significant benefit could be shown. REVIEWER'S CONCLUSIONS: Implications for practice. Methylxanthines might increase the chances of successful extubation of some preterm infants but the results of this meta-analysis do not allow firm recommendations to be made for clinical practice. One trial suggests that this benefit is principally in infants of extremely low birth weight extubated in the first week. There are no trial data to support the routine use of methylxanthines for the extubation of infants with a birth weight over 1000 gms or those that are older than one week. Implications for research. Further trials are required comparing methylxanthines with placebo for extubation of very preterm infants. There is a need to stratify infants by gestational age (a better indicator of immaturity) rather than birth weight in future studies. Caffeine, with its wider therapeutic margin (Blanchard 1992) would be the better treatment to evaluate against placebo. Side effects and neuro-developmental status at follow up should be included in as outcomes.

Caffeine↗

PubMed2000

Methylxanthine treatment for apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Methylxanthines have been used to stimulate breathing and prevent apnea and its consequences. OBJECTIVES: The objective of this review is to determine if methylxanthine treatment in preterm infants with recurrent apnea leads to a clinically important reduction in apnea and use of intermittent positive pressure ventilation (IPPV), without clinically important side effects. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which methylxanthine (theophylline or caffeine) was compared with placebo or no treatment for apnea in preterm infants, were included. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed independently by the two authors. Data were extracted independently by the two authors. Treatment effects were expressed as relative risk (RR) and risk difference (RD) and their 95% confidence intervals, using a fixed effect model. For significant results, the inverse of the risk difference (1/RD) was used to calculate the number needed to treat (NNT). MAIN RESULTS: The results of four trials which enrolled a total of 110 preterm infants with apnea indicate that methylxanthine therapy leads to a reduction in apnea and use of IPPV in the first 2 - 7 days. There are insufficient data to evaluate side effects and no data to examine effects within different gestational age groups. There are no trial data which examine long term effects. REVIEWER'S CONCLUSIONS: Methylxanthines are effective in reducing the number of apneic attacks and the use of mechanical ventilation in the two to seven days after starting treatment. In view of its lower toxicity, caffeine would be the preferred drug. Although the safety of methylxanthine therapy has been suggested in cohort studies, there are no trial data on longterm outcome. In order to indicate which infants are likely to benefit from treatment, there is a need for stratification by gestation and/or other risk factors in future studies. In any future studies the longer term effects of treatment on growth and development should be evaluated.

Apnea↗

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

Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage.

BACKGROUND: Preterm infants are at risk of periventricular haemorrhage. This can damage the brain and lead to neurodevelopmental abnormalities, including cerebral palsy. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain. OBJECTIVES: The objective of this review was to assess the benefits and harms of giving phenobarbital to women at risk of imminent very preterm birth with the primary aim of preventing periventricular haemorrhage in the infant. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies. Date of last search: December 1998. SELECTION CRITERIA: Randomised trials with reported data which compare outcomes, such as neonatal mortality, neonatal neurological and other morbidity, longterm neurodevelopment and maternal morbidity, following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo. DATA COLLECTION AND ANALYSIS: Assessments of trial eligibility, quality and data extractions were done by the two authors independently. Eligible trials were included in the initial analysis and prespecified sensitivity analyses done to evaluate the effect of trial quality. MAIN RESULTS: Over 1600 women were entered into the eight trials included. Analyses showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (relative risk 0.75, 95% confidence interval 0.65 to 0.88) and severe grades PVH (3 and 4) (relative risk 0.49, 95% confidence interval 0.32 to 0.74) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by the earlier trials which were of poorer quality and contributed excessive weight in the analysis due to their higher rates of severe PVH. Over time, and with improved trial quality, these beneficial effects disappeared. No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow-up assessed between 18-36 months of age. Maternal sedation was more likely in women receiving phenobarbital. REVIEWER'S CONCLUSIONS: Phenobarbital administration to women prior to preterm birth cannot be recommended for routine clinical practice. Any future trials should examine the effects of phenobarbital prior to preterm birth at gestational ages with a high risk of PVH, stratify for gestational age and ensure minimal exclusions after randomisation. Neurodevelopmental status at follow-up should be measured as the most important outcome.

Central Nervous System Agents↗

PubMed2000

Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage.

BACKGROUND: Preterm infants are at risk of periventricular haemorrhage. This can damage the brain and lead to neurodevelopmental abnormalities, including cerebral palsy. It has been suggested that vitamin K might improve coagulation in preterm infants. OBJECTIVES: The objective of this review was to assess the effects of vitamin K administered to women at risk of imminent very preterm birth to prevent periventricular haemorrhage and associated neurological injury in the infant. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, Cochrane Controlled Trials Register, and bibliographies up to January 1999. SELECTION CRITERIA: Randomised or quasi-randomised trials of vitamin K administered parenterally or orally to women at risk of imminent preterm birth. The primary outcomes were neonatal mortality, neonatal neurological morbidity, as measured by the presence of periventricular haemorrhage (PVH) on ultrasound during the first week of life, and long term neurodevelopment. Secondary outcomes included other neonatal morbidity and any maternal side effects. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. MAIN RESULTS: Five trials were included, involving more than 420 women. The trials were of variable quality. Antenatal vitamin K was associated with a non-significant trend to a reduction in all grades of periventricular haemorrhage (relative risk (RR) 0.82, 95% confidence interval (CI) 0.67-1.00) and in severe PVH (grades 3 and 4) (RR 0.75, 95% CI 0.45-1.25) for babies receiving prenatal vitamin K compared with control babies. This trend disappeared when poorer quality trials were excluded. Information on neurodevelopment was given for a small sample of children in one trial and no differences were seen. REVIEWER'S CONCLUSIONS: Vitamin K administered to women prior to very preterm birth does not appear to be able to significantly prevent periventricular haemorrhages in preterm infants.

Cerebral Hemorrhage↗

PubMed2000

Caffeine versus theophylline for apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Two forms of methylxanthine (caffeine and theophylline) have been used to stimulate breathing and so prevent apnea and its consequences. OBJECTIVES: In preterm infants with recurrent apnea, does caffeine treatment compared to theophylline treatment lead to a clinically important reduction in apnea and use of mechanical ventilation without clinically important side effects? SEARCH STRATEGY: Standard strategies of the Neonatal Review Group were used. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (see main text for strategy), previous reviews including cross references, abstracts conferences and symposium proceedings, expert informants, journal handsearching mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof Y. Ogawa. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation in which caffeine was compared with theophylline for the treatment of apnea were eligible. Trial quality and eligibility were assessed independently by each author. There must have been an effort to exclude specific causes of apnea. Measures of the severity of apnea as well as the response to treatment must have been consistent with an evaluation of 'clinical apnea' as defined by the American Academy of Pediatrics (Nelson 1978). DATA COLLECTION AND ANALYSIS: Standard method of Neonatal Review Group was used. Each author assessed eligibility, trial quality and extracted data separately, then compared and resolved differences. Results are expressed as relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) was calculated. MAIN RESULTS: There is no difference in the failure rate (< 50% reduction in apnea/bradycardia) of treatment with caffeine or theophylline at 1-3 (two studies) or 5-7 days (one study). There is a higher mean rate of apnea in the standard caffeine group at 1-3 days [three studies, mean diff. 0.398 (0.334,0.463) /100min] but not at 5-7 days (two studies). Side effects, as indicated by tachycardia or feed intolerance leading to change in dosing, are lower in the caffeine group [typical RR 0.17 (0.04,0.72), RD -0.285 (-0.467,-0.104), NNT 3.5 (2.1, 9.6)]. This was consistent across the three studies. No trial reported the use of IPPV and no data are available to assess effects on growth and development. REVIEWER'S CONCLUSIONS: Caffeine appears to have similar short term effects on apnea/bradycardia to theophylline. In view of the other therapeutic advantages of caffeine (a higher therapeutic ratio, more reliable enteral absorption and a longer half life) this is the preferred treatment for apnea in preterm infants. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials.

Apnea↗

PubMed2000

Intravenous dexamethasone for extubation of newborn infants.

BACKGROUND: Endotracheal tubes are foreign bodies that may injure the upper airway causing laryngeal edema. This in turn may result in failure of extubation in preterm infants. Corticosteroids have been used prophylactically to reduce upper airway obstruction and facilitate extubation. OBJECTIVES: In newborn infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV), what are the effects of intravenous corticosteroids on the incidence of endotracheal reintubation, stridor, atelectasis and adverse side effects? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH search terms "dexamethasone", "extubat*" and "exp infant, newborn"), 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. Y. Ogawa. SELECTION CRITERIA: Trials were included which used random or quasi-random patient allocation, and which compared intravenous steroids given immediately prior to a planned extubation with placebo. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors and analysed in Revman for all trials. Prespecified subgroup analyses were performed to examine differences in response between infants at high risk for upper airway edema and those receiving routine prophylaxis prior to extubation. MAIN RESULTS: Administration of dexamethasone prior to extubation significantly reduced the need for reintubation of the trachea. This result applies to both the high risk group and to the total population of infants enrolled. However, the incidence of extubation failure was zero in the trial that attempted to exclude infants at high risk of airway edema. The side effects of higher blood sugar levels and glycosuria were found in the 2 trials where these were sought. REVIEWER'S CONCLUSIONS: Implications for practice Dexamethasone reduces the need for endotracheal reintubation of neonates after a period of IPPV. In view of the lack of effect in low risk infants and the documented and potential side effects, it appears reasonable to restrict its use to infants at increased risk for airway edema and obstruction, such as those who have received repeated or prolonged intubations. Implications for research Issues of dosage and applicability to the extremely low birthweight population could be addressed in future trials. Longer term outcomes such as chronic lung disease, duration of assisted ventilation and length of hospital stay should also be examined.

Anti-Inflammatory Agents↗

PubMed2000

Elective high frequency jet ventilation versus conventional ventilation for respiratory distress syndrome in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: The objective of this review was to determine whether the elective (commencing soon after initiation of mechanical ventilation) use of high frequency jet ventilation (HFJV), as compared to conventional ventilation (CV) in preterm infants with respiratory distress syndrome (RDS), would decrease the incidence of chronic lung disease (CLD) without adverse effects. SEARCH STRATEGY: Randomized trials from MEDLINE were identified by means of MeSH and text words 'high frequency ventilation', 'high frequency jet ventilation', 'jet ventilation' from the years 1980 to 1997. The EMBASE database, the Oxford Database of Perinatal Trials, the Neonatal Trials Register of the Neonatal Review Group of the Cochrane Collaboration and the Cochrane library were also accessed. Proceedings of recent SPR/APS meetings were hand searched. Information was obtained from experts in the field, and cross references were checked. SELECTION CRITERIA: All randomized controlled trials of elective high frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks GA or with a birth weight less than 2000 gms with respiratory distress were included in the systematic review. Trials which used HFJV to 'rescue' preterm infants due to severe respiratory distress usually beyond 24 hours, and trials that used HFJV for a mandatory time period and then switched back to CV, were not included in this review. DATA COLLECTION AND ANALYSIS: The standard methods of the Neonatal Cochrane Review Group were used, including independent trial assessment and data extraction. Data were analysed 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 outcomes were calculated. MAIN RESULTS: Overall analysis of the three trials showed that HFJV is associated with a reduction in CLD at 36 weeks postmenstrual age in survivors [RR 0.58 (0.34, 0. 98), RD -0.138 (-0.268, -0.007), NNT 7 (4, 90)]. The use of home oxygen therapy was evaluated in only one study (Keszler 1997) and a lower rate was found in the HFJV group [RR 0.24 (0.07, 0.79), RD -0. 176 (-0.306, -0.047), NNT 5 (3, 21)]. Overall there was a trend towards an increase in the risk of PVL in the HFJV group, which was not significant. Subgroup analyses shows a significant increase in risk of PVL in the trial by Wiswell 1996 [RR 5.0 (1.19, 21.04), RD 0.250 (0.069, 0.431), NNH 4.0 (2.3,14.5)] where a 'low volume strategy' was the standard protocol for HFJV. In the other trial by Keszler 1997, where the intention was to use a 'high volume strategy', there was no significant difference in the incidence of PVL, RR 0.42 (0.14, 1.30). In the overall analysis, there were no significant differences in the incidence of neonatal mortality, IVH all grades or in grades 3 or 4 IVH. In the subgroup where 'low volume strategy' was used there was a non-significant trend toward an increase in risk of IVH all grades and grades 3 or 4 IVH. REVIEWER'S CONCLUSIONS: The overall analysis shows a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern is the significant increase in acute brain injury in one trial which used lower mean airway pressures when ventilating with HFJV. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to routinely ventilate premature infants with HFJV safely, ventilation with HFJV cannot be recommended for preterm infants with RDS.

High-Frequency Ventilation↗

PubMed2000

Kinesthetic stimulation for preventing apnea in preterm infants.

Apnea↗