Prophylactic methylxanthines for endotracheal extubation in preterm infants.

BACKGROUND: Weaning and extubating preterm infants on intermittent positive pressure ventilation (IPPV) for respiratory failure may be difficult. A significant contributing factor is thought to be the relatively poor respiratory drive and tendency to develop hypercarbia and apnoea, particularly in very preterm infants. Methylxanthine treatment started before extubation might stimulate breathing and increase the chances of successful weaning from IPPV. OBJECTIVES: To determine the effects of prophylactic methylxanthine treatment on the use of intubation and IPPV and other clinically important side effects in preterm infants being weaned from IPPV and in whom endotracheal extubation is planned. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2010), the Oxford Database of Perinatal Trials, MEDLINE (1966 to July 2010), CINAHL (1982 to July 2010) and EMBASE (1988 to July 2010). SELECTION CRITERIA: All published trials utilising random or quasi-random patient allocation in which treatment with methylxanthines (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. MAIN RESULTS: Seven studies were identified for inclusion. Methylxanthine treatment results in a reduction in failure of extubation within one week (summary RR 0.48, 95%CI 0.32 to 0.71; summary RD -0.27, 95%CI -0.39 to -0.15; NNT 4, 95%CI 3 to 7; six trials, 172 infants). There is significant heterogeneity in the RD meta-analysis perhaps related to the large variation in baseline rate in the control groups (range 20 to 100%).The CAP trial enrolled the largest number of infants, but did not report extubation rates. In the caffeine group, there were lower rates of bronchopulmonary dysplasia, PDA ligation, cerebral palsy and death or major disability at 18 to 21 months. Infants receiving caffeine had reduced postmenstrual ages at time of discontinuing oxygen therapy, positive pressure ventilation and endotracheal intubation. AUTHORS' CONCLUSIONS: Methylxanthines increase the chances of successful extubation of preterm infants within one week of age. Important neurodevelopmental outcomes are improved by methylxanthine therapy. In any future trials, there is a need to stratify infants by gestational age (a better indicator of immaturity than birth weight). Caffeine, with its wider therapeutic margin, would be the better treatment to evaluate against placebo.

Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data.

BACKGROUND: Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. METHODS: We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. FINDINGS: For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. INTERPRETATION: HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. FUNDING: Nestlé Belgium, Belgian Red Cross, and Dräger International.

Does observer bias contribute to variations in the rate of retinopathy of prematurity between centres?

PURPOSE: We aimed to indirectly assess the contribution from observer bias to between centre variability in the incidence of acute retinopathy of prematurity (ROP). METHODS: The Australian and New Zealand Neonatal Network (ANZNN) collected data on the highest stage of acute ROP in either eye in 2286 infants born at less than 29 weeks in 1998-1999 and cared for in one of 25 neonatal intensive care units (NICUs). Chi-squared analysis was used to detect differences in the proportion of stages of ROP for each neonatal intensive care unit. These proportions were compared with those reported in two large studies of treatment for ROP. RESULTS: The incidence of acute ROP in the ANZNN cohort was 42% and the ratio of stage 1:2:3 ROP was 1.5:1.9:1. There was considerable variation in both the incidence of acute ROP and the proportions with stage 1:2:3 ROP between centres. A chi-squared test determined that the assignment of stages 1, 2 and 3/4 ROP was not independent of centre (chi(2)(48) = 165.2; P < 0.0001). Treatment of stage 3 ROP varied between 15% and 120%, indicating some eyes were treated at less than stage 3. CONCLUSION: The data are highly suggestive of observer bias contributing to the observed between centre variation in the incidence of acute ROP. In neonatal intervention studies where acute ROP is an outcome it would seem important to have an accreditation process for examining ophthalmologists, and there are similar arguments for neonatal networks which collect these data.

Using hospital discharge data for determining neonatal morbidity and mortality: a validation study.

BACKGROUND: Despite widespread use of neonatal hospital discharge data, there are few published reports on the accuracy of population health data with neonatal diagnostic or procedure codes. The aim of this study was to assess the accuracy of using routinely collected hospital discharge data in identifying neonatal morbidity during the birth admission compared with data from a statewide audit of selected neonatal intensive care (NICU) admissions. METHODS: Validation study of population-based linked hospital discharge/birth data against neonatal intensive care audit data from New South Wales, Australia for 2,432 babies admitted to NICUs, 1994-1996. Sensitivity, specificity and positive predictive values (PPV) with exact binomial confidence intervals were calculated for 12 diagnoses and 6 procedures. RESULTS: Sensitivities ranged from 37.0% for drainage of an air leak to 97.7% for very low birthweight, specificities all exceeded 85% and PPVs ranged from 70.9% to 100%. In-hospital mortality, low birthweight (< or =1500 g), retinopathy of prematurity, respiratory distress syndrome, meconium aspiration, pneumonia, pulmonary hypertension, selected major anomalies, any mechanical ventilation (including CPAP), major surgery and surgery for patent ductus arteriosus or necrotizing enterocolitis were accurately identified with PPVs over 92%. Transient tachypnea of the newborn and drainage of an air leak had the lowest PPVs, 70.9% and 83.6% respectively. CONCLUSION: Although under-ascertained, routinely collected hospital discharge data had high PPVs for most validated items and would be suitable for risk factor analyses of neonatal morbidity. Procedures tended to be more accurately recorded than diagnoses.