Antenatal steroids and fluid balance in very low birthweight infants.

OBJECTIVES: To determine if insensible water loss (IWL) differed between infants exposed or not exposed antenatally to corticosteroids and to explore possible mechanisms for the early postnatal diuresis associated with antenatal steroid exposure. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Level three neonatal intensive care unit. PATIENTS: Ninety six infants, median gestational age 27.5 weeks (range 23-33). MAIN OUTCOME MEASURES: Comparison of the IWL, urine output and osmolality, fluid input, electrolyte imbalance, respiratory illness severity (as assessed by surfactant requirement, maximum peak inspiratory pressure, and inspired oxygen concentration), and cardiovascular status (as assessed by inotrope requirement) between infants with antenatal corticosteroid exposure and gestational age matched controls. RESULTS: The infants exposed to antenatal steroids differed significantly from the controls in having both a lower IWL (p = 0.0135) and a higher urine output (p = 0.0036) on day 1, and fewer developed hyponatraemia (p = 0.027) on day 2. Fewer of those exposed to antenatal steroids required inotropes (p = 0.06), but their respiratory status was similar to that of the controls. CONCLUSIONS: Infants exposed to antenatal corticosteroids have a lower IWL. The results suggest that greater skin maturation, but also better perfusion rather than less severe respiratory status, explains the early diuresis in infants exposed to antenatal steroids.

A comparison of arginine vasopressin levels and fluid balance in the perinatal period in infants who did and did not develop chronic oxygen dependency.

Arginine vasopressin (AVP) levels on days 1, 3 and 5 and fluid balance in the perinatal period were assessed in 60 infants, median gestational age 27 weeks (range 24-33). Fluid input and output, urine osmolality and episodes of hyponatraemia were recorded on a daily basis. Forty-one infants subsequently developed chronic lung disease (CLD), they were more immature, of lower birthweight and had higher AVP levels on days 3 and 5 (p < 0.05) than the rest of the cohort. Despite similar levels of fluid input, compared to the non-CLD infants, those who developed CLD had higher urine osmolalities on days 1, 5, 6 and 7 (p < 0.05), but there were not significant differences between the two groups regarding urine output or episodes of hyponatraemia. Logistic regression analysis revealed AVP levels on day 3 were significantly correlated with the duration of oxygen dependency independent of other factors. We conclude elevated AVP levels in the perinatal period are associated with CLD development, but our results suggest they have little functional significance.

Randomised trial of fluid restriction in ventilated very low birthweight infants.

BACKGROUND: Fluid restriction has been reported to improve survival of infants without chronic lung disease (CLD), but it remains unknown whether it reduces CLD in a population at high risk of CLD routinely exposed to antenatal steroids and postnatal surfactant without increasing other adverse outcomes. AIM: To investigate the impact of fluid restriction on the outcome of ventilated, very low birthweight infants. STUDY DESIGN: A randomised trial of two fluid input levels in the perinatal period was performed. A total of 168 ventilated infants (median gestational age 27 weeks (range 23-33)) were randomly assigned to receive standard volumes of fluid (60 ml/kg on day 1 progressing to 150 ml/kg on day 7) or be restricted to about 80% of standard input. RESULTS: Similar proportions of infants on the two regimens had CLD beyond 28 days (56% v 51%) and 36 weeks post conceptional age (26% v 25%), survived without oxygen dependency at 28 days (31% v 27%) and 36 weeks post conceptional age (58% v 52%), and developed acute renal failure. There were no statistically significant differences between other outcomes, except that fewer of the restricted group (19% v 43%) required postnatal steroids (p < 0.01). In the trial population overall, duration of oxygen dependency related significantly to the colloid (p < 0.01), but not crystalloid, input level; after adjustment for specified covariates, the hazard ratio was 1.07 (95% confidence interval 1.02 to 1.13). CONCLUSIONS: In ventilated, very low birthweight infants, fluid restriction in the perinatal period neither reduces CLD nor increases other adverse outcomes. Colloid infusion, however, is associated with increased duration of oxygen dependency.

Elective use of nasal continuous positive airways pressure following extubation of preterm infants.

UNLABELLED: The aim of this study was to determine whether elective use of nasal continuous positive airways pressure (CPAP) following extubation of preterm infants was well tolerated and improved short- and long-term outcomes. A randomized comparison of nasal CPAP to headbox oxygen was undertaken and a meta-analysis performed including similar randomized trials involving premature infants less than 28 days of age. A total of 150 infants (median gestational age 30 weeks, range 24-34 weeks) were randomized in two centres. Fifteen nasal CPAP infants and 25 headbox infants required increased respiratory support post-extubation and 15 nasal CPAP infants and nine headbox infants required reintubation (non significant). Eight infants became intolerant of CPAP and were changed to headbox oxygen within 48 h of extubation; 19 headbox infants developed apnoeas and respiratory acidosis requiring rescue nasal CPAP, 3 ultimately were re-intubated. Seven other trials were identified, giving a total number of 569 infants. Overall, nasal CPAP significantly reduced the need for increased respiratory support (relative risk, 0.57, 95% CI 0.43-0.73), but not for re-intubation (relative risk 0.89, 95% CI 0.68-1.17). Nasal CPAP neither influenced significantly the intraventricular haemorrhage rate reported in four studies (relative risk 1.0, 95% CI 0.55, 1.82) nor that of oxygen dependency at 28 days reported in six studies (relative risk 1.0, 95% CI 0.8, 1.25). In two studies nasal CPAP had to be discontinued in 10% of infants either because of intolerance or hyperoxia. CONCLUSION: Elective use of nasal continuous positive airways pressure post-extubation is not universally tolerated, but does reduce the need for additional support.

Prediction of extubation failure in preterm neonates.

UNLABELLED: The aim of this study was to compare the results of lung function measurements made before and after extubation and ventilator settings recorded immediately prior to extubation with regard to their ability to predict extubation success in mechanically ventilated, prematurely born infants. Immediately after extubation all infants were nursed in an appropriate amount of humidified oxygen bled into a headbox. Functional residual capacity, spontaneous tidal volume and compliance of the respiratory system were measured both within 4 h before and within 24 h after extubation. The peak inspiratory pressure and inspired oxygen concentration immediately prior to extubation were recorded. The results were related to extubation failure: requirement for continuous positive airways pressure or re-ventilation within 48 h of extubation. A total of 30 infants, median gestational age 29 weeks (range 25-33 weeks) were studied at a median postnatal age of 3 days (range 1-6 days). Extubation failed in ten infants, who differed significantly from the rest of the cohort with regard to their post extubation functional residual capacity (FRC) (median 23, range 15.6-28.7 ml/kg versus 28.6, range 18.1-39.2 ml/kg, P<0.01) and their requirement for a higher inspired oxygen concentration post extubation (median 0.30, range 0.21-0.40 versus 0.22, range 0.21-0.36, P<0.05). An FRC of less than 26 ml/kg post extubation had the highest positive predictive value in predicting extubation failure. CONCLUSION: A low lung volume performed best in predicting extubation failure when compared to the results of other lung function measurements and commonly used 'clinical' indices, i.e. ventilator settings. A low gestational age, however, was a better predictor of extubation failure than a low lung volume.

Effect on lung function of continuous positive airway pressure administered either by infant flow driver or a single nasal prong.

UNLABELLED: The aim of this study was to assess if continuous positive airways pressure (CPAP) delivered by an infant flow driver (IFD) was a more effective method of improving lung function than delivering CPAP by a single nasal prong. A total of 36 infants (median gestational age 29 weeks, range 25-35 weeks) were studied, 12 who received CPAP via an IFD, 12 who received CPAP via a single nasal prong and 12 without CPAP. CPAP was administered post extubation if apnoeas and bradycardias or a respiratory acidosis developed or electively if the infant was of birth weight <1.0 kg. Lung function was assessed by the supplementary oxygen requirement and measurement of compliance of the respiratory system using an occlusion technique. Assessments were made immediately prior to and after 24 h of CPAP administration and at similar postnatal ages in the non-CPAP group. The infants who did not require CPAP had better lung function (non significant) than the other two groups before they received CPAP. After 24 h, lung function had improved in both CPAP groups to the level of the non CPAP infants. The supplementary oxygen requirements of all three groups decreased over the 24 h period, but this only reached significance in the single nasal prong group (P<0.05). Four infants supported by the IFD, but none with a single nasal prong, became hyperoxic. CONCLUSION: Continuous positive airways pressure administration via the infant flow driver appears to offer no short-term advantage over a single nasal prong system when used after extubation in preterm infants.

Randomized trial of two levels of fluid input in the perinatal period--effect on fluid balance, electrolyte and metabolic disturbances in ventilated VLBW infants.

The aim of this study was to determine whether fluid restriction does indeed significantly increase acute adverse effects. One-hundred-and-sixty-eight ventilated infants, median gestational age 27 wk (range 23-33) and birthweight 953 g (range 486-1500), entered into a randomized controlled trial of two fluid regimes. Infants on regime A were to be prescribed 60 ml/kg of fluids on day 1 which was gradually increased over the first week to 150 ml/kg, infants on fluid regime B were to be prescribed approximately 20% less fluid over the first week. Daily fluid input and output were recorded. Serum electrolytes, bilirubin, creatinine and urine osmolalities were measured daily. Arginine vasopressin levels were assessed on days 1, 3 and 5. Episodes of jaundice, hypoglycaemia and hypotension requiring treatment were noted. Infants on regime B actually received overall 11% and, in the first 4 days, 19% less fluid than those on regime A (p < 0.001). There were no statistically significant differences in the occurrence of episodes of jaundice, hypotension, hypoglycaemia, hypernatraemia or hyponatraemia between infants on the two regimes. Although the infants on regime B had significantly higher urine osmolalities and lower urine output for most of the perinatal period, their median creatinine and arginine vasopressin levels did not differ significantly from those on regime A. We conclude that fluid restriction to less than 90% of usual maintenance fluids is not associated with an excess of acute adverse effects.

Early prediction of chronic oxygen dependency by lung function test results.

Chronic oxygen dependency (COD) is a common sequela to very premature birth. Steroid therapy may reduce COD if given within the first 2 weeks, but has important side effects. It is, therefore, crucial to identify an accurate predictor of COD and hence only expose high-risk infants to intervention therapy. The aim of this study was to determine if, within 48 hr of birth, abnormal lung function predicted COD and whether such results performed better than readily available clinical data. Results from 100 consecutive, very low birth-weight infants, median gestation age 28 weeks (range, 24-33), who were ventilated within 6 hr of birth and survived beyond 36 weeks postconceptional age (PCA), were analyzed. Lung volume was assessed by measurement of functional residual capacity (FRC) using a helium gas dilution technique, and compliance was measured using either a passive inflation or an occlusion technique. The maximum peak inflating pressure and inspired oxygen concentration within the first 48 hr were recorded. The infants who remained oxygen-dependent beyond 28 days (n = 58) and 36 weeks PCA (n = 24) differed from the rest in being more immature (P < 0.001), more had a patent ductus arteriosus, and they had both a lower median lung volume (P < 0.001) and lower compliance (P < 0.01) on day 2. An FRC <19 mL/kg and a low gestational age were the most accurate predictors of COD at 28 days. An FRC <19 mL/kg on day 2 remained the best predictor of COD beyond 28 days if only the 50 infants whose gestational age was < or = 28 weeks were considered. We conclude that demonstration of a low lung volume in the first 48 hr helps to identify infants who might benefit from therapy aimed at preventing COD.

Comparison of the effect of two fluid input regimens on perinatal lung function in ventilated infants of very low birthweight.

UNLABELLED: Fluid overload worsens respiratory failure; conversely, fluid restriction has been associated with a higher survival rate without chronic lung disease. We therefore hypothesised that fluid restriction in the perinatal period might improve lung function in ventilated, prematurely born infants of very low birthweight. As a consequence, we compared in a randomised trial the effect of two fluid regimes on perinatal lung function. On one regime infants were to receive 60 ml/kg on day 1, increasing to 150 ml/kg by day 7, and on the other regime approximately 25% less fluid was to be prescribed. Lung function was assessed by measurement of functional residual capacity (FRC) and compliance. Measurements were made daily on days 1 to 5 and then on day 7. Ninety infants, median gestational age 28 weeks (range 23-33), were included in the study. There were no significant differences between the two groups regarding their gestational age or birthweight, or in the proportions who received antenatal steroids or postnatal surfactant. The infants on the restricted regime received significantly less fluid (P < 0.01). The only significant differences in lung function between the two groups, however, were that the infants on the restricted regime had a higher mean compliance on day 3, but thereafter the difference was reversed. Colloid intake, however, unfavourably affected lung function, total colloid intake being negatively correlated with both the area under the curve of birth-adjusted FRC (P=0.003) and compliance (P=0.001). CONCLUSION: We conclude that early fluid restriction appears to have very little impact on perinatal lung function.

Plasma arginine levels and the response to inhaled nitric oxide in neonates.

Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0. 05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2-53) mu mol/l, but not significantly lower than that of the controls (median 24, range 3-82 mu mol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.

A simple chest radiograph score to predict chronic lung disease in prematurely born infants.

A simple scoring system has been evaluated with regard to its ability to characterize the pre-term infant's chest radiograph appearance at 28 days and predict oxygen dependency beyond 36 weeks post-conceptional age (PCA). Chest radiographs taken at approximately 1 month of age in 42 infants (median gestational age 28 weeks) were assessed by the scoring system for the presence of fibrosis/interstitial shadows, cystic elements and degree of hyperinflation (maximum score 8). The system's results were then compared with those obtained using two previously published scoring systems. Using all three systems, there were significant differences in the scores of infants who were and were not oxygen dependent at 28 days (p < 0.001) and 36 weeks PCA (p < 0.001). For the three systems, the positive predictive values of a score of 3 or more to predict oxygen dependency at 36 weeks (PCA) were between 67% and 80% and similar receiver operating characteristic curves were obtained. We conclude that scoring only three abnormalities of the 28 day chest radiograph appearance of pre-term infants gives useful predictive information.

Blood pressure rhythms during the perinatal period in very immature, extremely low birthweight neonates.

The aim of this study was to investigate if blood pressure (BP) rhythms were present in the perinatal period in very immature infants. Twenty-two infants, median gestational age 24-28 weeks, who had indwelling arterial lines with undamped arterial BP waveforms, were studied. The infants were all receiving intensive care under constant conditions. The hourly mean, systolic and diastolic BPs on days 2 and 7 were examined. A cosinor analysis of the mean BP was performed examining period lengths of 4, 8, 12, 16, 20, and 24 h to determine whether ultradian and/or circadian rhythms existed. On day 2, but not day 7, the mean and systolic BPs showed significant variation and circadian and ultradian rhythms were demonstrated. We suggest that maternal influences may be responsible for the BP rhythms noted in very immature infants on day 2.

A radiographic method for assessing lung area in neonates.

The aim of this study was to determine whether computer assisted analysis of lung area on the chest radiograph reliably predicted lung volume in neonates. Anteroposterior chest radiographs taken for clinical purposes were scanned and analysed using a Power Macintosh computer with a Wacom A5 Ultra Pad and NIH image software. The cardiac, mediastinal and thymic densities and areas of perihilar and lobar consolidation were subtracted from the thoracic area to give the lung area. This was compared with lung volume, assessed by measurement of functional residual capacity (FRC), within 1 h of the chest radiograph being performed. 50 infants, median gestational age 30 weeks (range 24-43) were studied. Their median lung area was 11.23 cm2 (range 0.82-28.53) and lung volume 28 ml (range 3-103). The intraobserver and interobserver coefficients of repeatability of lung area were 1.0 cm2 and 1.06 cm2, respectively. Lung area correlated significantly with FRC (r = 0.60, p < 0.0001). It is concluded that computer assisted analysis of the chest radiograph lung area is a reliable method of assessing lung volume in neonates.

Comparison of two inspiratory: expiratory ratios during high frequency oscillation.

UNLABELLED: The aim of this study was to compare gas exchange and volume delivery during high frequency oscillation at two frequently used inspiratory:expiratory (I:E) ratios: 1:2 and 1:1, other oscillatory settings being kept constant. A group of 13 infants with respiratory distress syndrome, median gestational age 28 weeks (range 23-36) and postnatal age 1 day (range 1-8) were studied. At the I:E ratio of 1:1 compared to 1:2 the median paCO(2) was lower, P < 0.05 (30 mmHg, range 22-47 vs 34 mmHg, range 27-46) and the volume delivered higher, P < 0.01 (2.6 ml/kg, range 1.2-5.6 vs 2.0 ml/kg, range 1.0-3.9). There was no significant difference in oxygenation levels at the two I:E ratios. In a related in vitro study, changing the I:E ratio from 1:2 to 1:1 increased the mean airway pressure by a median of 8.6% (range 2.9-28.1%). CONCLUSION: Routinely maintained longer expiratory than inspiratory times during high frequency oscillation should be discouraged.

Outcome predictors in nitric oxide treated preterm infants.

UNLABELLED: Our aim was to identify factors predictive of death in preterm infants in whom inhaled nitric oxide was administered in response to poor oxygenation (oxygenation index > or =15). Of the 23 (median gestational age 28 weeks, range 24-36) infants consecutively so treated, 15 died. Non-survival was commoner in infants with air leaks (12 of 12, P < 0.002) and/or a change in their oxygenation index of less than 30% in response to inhaled nitric oxide administration (P < 0.05). CONCLUSION: In preterm infants given inhaled nitric oxide because of poor oxygenation, a diagnosis of airleak and a lack of initial response are predictive of death.

Substance misuse in early pregnancy and relationship to fetal outcome.

UNLABELLED: To establish the frequency of substance misuse in early pregnancy in an urban UK population, 807 consecutive positive pregnancy test urine samples were screened for a range of drugs, including cotinine as an indicator of maternal smoking habits. A positive test for cannabinoids was found in 117 (14.5%) samples. Smaller numbers of samples were positive for other drugs:- opiates (11), benzodiazepines (4), cocaine (3) and one each for amphetamines and methadone. Polydrug use was detected in nine individuals. Only two samples tested positive for ethanol. The proportion with a urine cotinine level indicative of active smoking was 34.3%. The outcome of the pregnancy was traced for 288 subjects. Cannabis use was associated with a lower gestational age at delivery (P < 0.005), an increased risk of prematurity (P < 0.02) and reduction in birth weight (P < 0.002). Whilst maternal smoking was associated with a reduction in infant birth weight (P < 0.05), this was less pronounced than the effect of other substance misuse. CONCLUSION: This study suggests that one in six women in South London are using drugs in early pregnancy and that cannabinoid use is associated with a poorer pregnancy outcome.

Neonatal lung function in very immature infants with and without RDS.

Some infants, despite being born at low gestations (< 28 weeks gestational age) do not develop RDS and are not surfactant treated. The changes in lung function during the neonatal period in such infants have not been explored, hence it is unknown whether they are similar to those of surfactant treated infants with RDS of similar gestational age. Such data would facilitate assessment of the impact of surfactant administration on the lung function abnormalities of very immature infants with RDS. We, therefore, compared the results of neonatal lung function measurements from immature infants with RDS who received surfactant to those from infants with non-RDS respiratory distress not so treated and matched to the RDS infants for gestational age and within 10% of birthweight. Compliance and functional residual capacity (FRC) were measured daily for the first five days and then at 1, 2 and 4 weeks in 16 infants, median gestational age 27 weeks (range 25-27 weeks). Although exogenous surfactant administration to the immature infants with RDS was associated with improvements in lung function, the non RDS, non surfactant treated infants had both higher compliance (p < 0.05) and lung volumes (p < 0.01) throughout the perinatal period. These results demonstrate surfactant administration does not fully correct the perinatal lung function abnormalities of very immature infants with RDS.

Volume delivery during high frequency oscillation.

AIM: To examine the delivered volume during "high volume strategy" high frequency oscillation, used as rescue treatment in preterm infants; and to identify factors, other than frequency and oscillatory amplitude, influencing the magnitude of volume delivery. METHOD: Twenty infants (median gestational age 29 weeks) were studied on 45 occasions. Two oscillator types were used (SensorMedics and SLE). Delivered volume was measured under clinical conditions with the arterial blood gases within a predetermined range. A specially calibrated pneumotachograph system was used. RESULTS: Overall, the median delivered volume was 2.4 ml/kg (range 1.0 to 3.6 ml/kg); on 32 occasions the delivered volume was greater than 2.0 ml/kg and on seven greater than 3.0 ml/kg. The delivered volume related significantly to disease severity; there was an inverse correlaton between delivered volume and both the oxygenation index (OI) (r = -0.51) and AaDO2 (r = -0.54). CONCLUSION: Delivered volume during HFO may, in certain infants, exceed the anatomical dead space, permitting some direct alveolar ventilation.