Vasiliki Kavvadia

Substance misuse in early pregnancy and relationship to fetal outcome

Abstract 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.

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. Key messages High fluid volumes increase the likelihood of a PDA, a risk factor for CLD development One of four previous randomised trials showed that fluid restriction improved outcome—that is, a lower mortality in a relatively mature population We now show in ventilated VLBW infants that fluid restriction in the perinatal period does not reduce CLD; colloid infusion, however, increases duration of oxygen dependency

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

Abstract 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 re-intubation (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.

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

Abstract 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.

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 correlation 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.

Colloid infusion in the perinatal period and abnormal neurodevelopmental outcome in very low birth weight infants

Abstract. In very low birth weight (VLBW) infants, colloid infusion is associated with impaired perinatal lung function and increased oxygen dependency duration. The aim of this study was to determine whether perinatal colloid infusion was associated with abnormal neurodevelopmental outcome. All perinatal fluid input (crystalloid and colloid) given to VLBW infants entered into a randomised trial was recorded. At 1 and/or 2 years, the neurodevelopmental status of VLBW infants was routinely assessed. Of 131 survivors, median gestational age 27 weeks (range 23–33 weeks), 95 were seen at follow-up. Nineteen had abnormal neurodevelopmental outcome and differed significantly from the rest of the cohort with regard to their birth weight, magnitude of colloid infusion received and the proportions who had received postnatal steroids, suffered prolonged oxygen dependency or having had intracerebral haemorrhage/periventricular leucomalacia development. Regression analysis demonstrated that only colloid infusion related significantly to abnormal neurodevelopmental outcome independent of other variables. Conclusion: These data suggest that colloid infusion should be used with caution in the perinatal period.

Perioperative assessment of respiratory compliance and lung volume in infants with congenital diaphragmatic hernia: Prediction of outcome

BACKGROUND/PURPOSE Infants who have congenital diaphragmatic hernia (CDH) have high mortality and morbidity. The aim of this study was to determine the relative ability of the results of serial measurements of compliance of the respiratory system (CRS) and lung volume (functional residual capacity (FRC)) to predict poor outcome: death or oxygen dependency at 28 days. In addition, the authors wished to document the evolution of any lung function abnormalities during the perioperative period. METHODS Daily measurements of CRS and FRC were made in the first week of life and subsequently during week 2 in 16 infants who had a median gestational age of 38 weeks and birth weight of 3.2 kg. RESULTS Seven infants had a poor outcome: five died and two others remained oxygen dependent beyond 28 days. The infants who had a poor outcome were characterized on day 1 by a significantly lower CRS, but not FRC (P < .05). In comparison with results from day 1, the median CRS of the infants overall had significantly improved only by week 2 (P < .05), there was no such significant change in FRC with increasing postnatal age. At week 2, only the CRS results differed significantly between those infants who had and who did not have poor outcome (P < .05). CONCLUSION The results of serial measurements of CRS, rather than FRC are the more useful predictor of outcome in infants who have CDH.

Diaphragmatic function in infants with surgically corrected anomalies.

Infants with surgically correctable anomalies, abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH) may have poor postnatal diaphragmatic function, because the low intra-abdominal pressure experienced by such patients in utero could result in impaired diaphragmatic development. Our objective was to compare postoperative diaphragmatic function of infants with CDH or AWD to that of gestational age-matched controls. Diaphragmatic function was assessed by measurement of the transdiaphragmatic pressure and maximum inspiratory pressure at the mouth generated during crying against an occlusion. In addition, the transdiaphragmatic pressure produced by unilateral and/or bilateral magnetic stimulation of the phrenic nerves (TwPdi) was examined. Lung volume was assessed by measurement of functional residual capacity (FRC) using a helium gas dilution technique. Ten infants with CDH, 26 with AWD infants (19 gastroschisis, seven exomphalos), and 36 gestational age-matched controls were studied. Compared with their matched controls, the eight CDH infants with left-sided defects had significantly lower left (p < 0.01) and right (p < 0.05) TwPdi and FRC (p < 0.01), and the gastroschisis infants, but not those with exomphalos, had significantly lower left and right TwPdi (p < 0.05). There were no significant differences in transdiaphragmatic pressure and maximum inspiratory pressure at the mouth between the CDH or AWD infants and the controls. Diaphragmatic function postoperatively is impaired in infants with CDH or gastroschisis.

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.

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

Abstract 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.