Neonatal seizures during extra corporeal membrane oxygenation support.

To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1-20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1-7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4-103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8-41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7-52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97-20.5, p = 0.002)Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: • Patients on ECMO are at a higher risk of seiures. • Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: • In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. • Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? • This study reports a 33% incidence of neonatal seizures during ECMO. • Neonates with seizures were 11 times more likely to have an abnormal brain scan. • The study captures the real-time approach of EEG monitoring. • Recommended cEEG monitoring should last at least 24 h for ECMO patients. • This is the first study to assess this in neonates only.

Transient abnormal myelopoiesis requiring advanced neonatal intensive care treatment.

AIM: Five to thirty percent of neonates with trisomy 21 develop transient abnormal myelopoiesis (TAM) with a high mortality rate. The aim of the study was to identify contributing factors that determine mortality and need for chemotherapy in this patient group. METHODS: Six-year, single-centre, retrospective study of neonatal TAM cases requiring admission to intensive care. Data were collected from electronic patient records, laboratory and genetic results. The odds ratio was calculated to assess the likelihood of neonates with certain clinical characteristics having short-term mortality and needing chemotherapy. RESULTS: Twenty-one neonates were studied with a mortality rate of 28%. Neonates requiring inotropic support (OR 19, 95% CI: 0.9-399, p = 0.05) and inhaled nitric oxide (iNO) (OR 13, 95% CI: 1.4-124.3, p = 0.03) were less likely to survive to discharge. Neonates needing mechanical ventilation (OR 14, 95% CI: 1.1-185.5, p = 0.04), or a white cell count >50 × 109/L (OR 27, 95% CI: 1.2-605.7, p = 0.04) were more likely to receive chemotherapy. CONCLUSION: A high mortality rate was identified in TAM neonates with symptomatic pulmonary hypertension (PH) needing active treatment strategies, such as inotropes and iNO. The presence of PH should be considered in the clinical management, prognosis and parental counselling.

Ventilatory Responses to Hypercarbia in Infants of Mothers Who Smoke and Misuse Substances.

The ventilatory response of infants of mothers who smoke and misuse substances and controls to carbon dioxide was assessed at 6-12 weeks and the perinatal period. Infants of mothers who smoke and misuse substances had a dampened response at the peak age of sudden infant death syndrome, greater than in the perinatal period.

In vitro assessment of the effect of proportional assist ventilation on the work of breathing.

UNLABELLED: During proportional assist ventilation, elastic and resistive unloading can be delivered to reduce the work of breathing (WOB). Our aim was to determine the effects of different levels of elastic and resistive unloading on the WOB in lung models designed to mimic certain neonatal respiratory disorders. Two dynamic lung models were used, one with a compliance of 0.4 ml/cm H2O to mimic an infant with respiratory distress syndrome and one with a resistance of 300 cm H2O/l/s to mimic an infant with bronchopulmonary dypslasia. Pressure volume curves were constructed at each unloading level. Elastic unloading in the low compliance model was highly effective in reducing the WOB measured in the lung model; the effective compliance increased from 0.4 ml/cm H2O at baseline to 4.1 ml/cm H2O at maximum possible elastic unloading (2.0 cm H2O/ml). Maximum possible resistive unloading (200 cm H2O/l/s) in the high-resistance model only reduced the effective resistance from 300 to 204 cm H2O/l/s. At maximum resistive unloading, oscillations appeared in the airway pressure waveform. CONCLUSION: Our results suggest that elastic unloading will be helpful in respiratory conditions characterised by a low compliance, but resistive unloading as currently delivered is unlikely to be of major clinical benefit. WHAT IS KNOWN: • During PAV, the ventilator can provide elastic and resistive unloading. What is New: • Elastic unloading was highly effective in reducing the work of breathing. • Maximum resistive unloading only partially reduced the effective resistance.

Volume-targeted versus pressure-limited ventilation in infants born at or near term.

Our aims were to determine whether volume-targeted ventilation (VTV) or pressure-limited ventilation (PLV) reduced the time to successful extubation and if any difference was explained by a lower work of breathing (WOB), better respiratory muscle strength or less thoracoabdominal asynchrony (TAA) and associated with fewer hypocarbic episodes. Infants born at ≥34 weeks of gestational age were randomised to VTV or PLV. The WOB was assessed by the transdiaphragmatic pressure time product, respiratory muscle strength by the maximum inflation (Pimax) and expiratory (Pemax) pressures and TAA assessed using uncalibrated respiratory inductance plethysmography. Forty infants, median gestational age of 39 (range 34-42) weeks, were recruited. The time to successful extubation did not differ between the two groups (median 25, range 2.5-312 h (VTV) versus 33.5, 1.312 h (PLV)) (p = 0.461). There were no significant differences between the groups with regard to the WOB, respiratory muscle strength or the TAA results. The median number of hypocarbic episodes was 1.5 (range 0-8) in the VTV group versus 4 (range 1-13) in the PLV group (p = 0.005). CONCLUSION: In infants born at or near term, VTV compared to PLV did not reduce the time to successful extubation but was associated with significantly fewer hypocarbic episodes. WHAT IS KNOWN: In prematurely born infants, volume-targeted ventilation (VTV) compared to pressure-limited ventilation (PLV) reduces bronchopulmonary dysplasia or death. In addition, VTV is associated in prematurely born infants with lower incidences of pneumothorax, intraventricular haemorrhage and hypocarbic episodes. WHAT IS NEW: Despite a high morbidity, few studies have investigated optimum ventilation strategies for infants born at or near term. In a RCT, we have demonstrated VTV versus PLV in infants ≥34 weeks gestation was associated with significantly fewer hypocarbic episodes.

Respiratory support practices in infants born at term in the United Kingdom.

Infants born at term requiring mechanical ventilation suffer significant mortality and morbidity, yet few studies have tried to identify the optimum respiratory support for such infants. We, therefore, hypothesised that practice would vary, particularly between different levels of neonatal care provision. The lead clinicians of all 212 UK neonatal units were asked to complete an electronic web-based survey regarding respiratory support practices for term-born infants. Survey questions included the level of neonatal care provided, number of term-born infants ventilated per annum, initial and rescue ventilation modes and whether surfactant or inhaled nitric oxide (NO) were used. The overall response rate was 82 %. A greater proportion of neonatal intensive care units (NICUs) compared to local neonatal units (LNUs) stated that they used volume-targeting, particularly for infants with RDS (p = 0.0006) or congenital pneumonia (p = 0.0005). High-frequency oscillatory ventilation was stated as initial mode by a greater proportion of NICUs compared to LNUs and special care units (SCUs), particularly for respiratory distress syndrome (p < 0.0001) or persistent pulmonary hypertension of the newborn (p < 0.001). Continuous mandatory ventilation was stated to be the rescue mode by a greater proportion of LNUs/SCUs compared to NICUs (p < 0.0001). Surfactant was stated to be most commonly given for respiratory distress syndrome (79 % of units) and MAS (61 % of units); surfactant use was lowest in SCUs (p < 0.0001); inhaled NO was infrequently used by LNUs and SCUs. Conclusions There was considerable variation in respiratory support practices for term-born infants, particularly between different levels of neonatal care provision.

Survey of sleeping position recommendations for prematurely born infants.

UNLABELLED: The risk of sudden infant death syndrome is increased in prematurely born infants compared to those born at term, particularly if they are either slept prone or on their side. The aim of this study was to determine whether a national campaign "Time to get back to sleep" had influenced the recommendations made by neonatal practitioners regarding the sleeping position for prematurely born babies prior to and after neonatal unit discharge. A questionnaire survey was sent to all UK neonatal units, of which 90% responded. The results were compared to those of a survey carried out prior to the national campaign. Analysis of the responses demonstrated that there was no significant difference in the proportion of units which recommended supine sleeping at least 1-2 weeks before discharge (78% versus 83%). Still, a minority of units provided written information for staff (26% versus 33%), but a greater proportion of units provided written information for parents (95% versus 90%, p = 0.047). All units recommended supine sleeping following discharge, and compared to the results of the previous survey, a smaller proportion of units additionally recommended side sleeping after discharge (8% versus 17%, p =0.01) and a greater proportion actively discouraged prone sleeping (62% versus 38%, p < 0.0001). CONCLUSIONS: The majority but, importantly, not all neonatal units are giving appropriate recommendations regarding sleeping position following neonatal unit discharge. These results highlight that further education of neonatal staff regarding appropriate sleeping position for prematurely born babies remains imperative.

The effects of sleeping position on ventilatory responses to carbon dioxide in premature infants.

BACKGROUND: The prone sleeping position, particularly in prematurely born infants, is associated with an increased risk of sudden infant death syndrome. A possible mechanism is an impaired ability to respond to respiratory compromise. The hypothesis that the ventilatory response to a carbon dioxide (CO(2)) challenge in convalescent, prematurely born infants would be lower in the prone compared with the supine position was therefore tested. METHODS: In each position, ventilatory responses to increasing levels of inspired CO(2) were assessed. The airway pressure change after the first 100 ms of an occluded inspiration (P(0.1)) and the maximum inspiratory pressure with an occluded airway during crying (P(imax)) were measured; the ratio of the P(0.1) to the P(imax) at each inspired CO(2) level and the slope of the P(0.1)/P(imax) response were calculated. Chest and abdominal wall asynchrony was assessed using inductance plethysmography and functional residual capacity (FRC) measured using a helium gas dilution technique. RESULTS: Eighteen infants with a median postmenstrual age of 35 (range 35-37) weeks were studied. In the prone versus the supine position, the mean P(0.1) (p=0.002), the mean P(imax) (p=0.006), the increase in P(0.1) with increasing CO(2) (p=0.007) and the P(0.1)/P(imax) response slope (p=0.007) were smaller. Thoracoabdominal asynchrony was not significantly influenced by position or inspired CO(2). FRC was higher in the prone position (p=0.019). CONCLUSIONS: Convalescent, prematurely born infants have a reduced ventilatory response to CO(2) challenge in the prone position, suggesting they may have an impaired ability to respond to respiratory compromise in that position.

Neonatal abstinence syndrome--postnatal ward versus neonatal unit management.

AIM: The aim of this cohort study was to test the hypothesis that caring for infants with neonatal abstinence syndrome (NAS) with their mothers on the postnatal ward rather than admit them to the neonatal unit would reduce treatment duration and length of hospital stay. RESULTS: The outcomes of infants with NAS cared for in 2002-2005 (Group A, n = 42) and 2006-2007 (Group B, n = 18) were compared. Group A infants were admitted to the neonatal unit for assessment and treatment as necessary, but Group B infants remained on the postnatal ward with their mother. Sixty infants (median gestational age 39, range 26-42 weeks) were included in the study. The proportion of infants in Group B compared to Group A requiring treatment for NAS was lower (45% versus 11%, p = 0.012) and the durations of treatment (mean 12.7 versus 7.3 days, p = 0.05) and hospital stay (mean 19.8 versus 15.9 days, p = 0.012) were shorter in Group B. No infant in either group was readmitted within the next 2 months. CONCLUSIONS: These results suggest caring for infants with NAS on the postnatal ward rather than the neonatal unit reduces the need for treatment and duration of hospital stay.

Normal neurological outcome in two infants treated with exchange transfusions born to mothers with Crigler-Najjar Type 1 disorder.

Patients with Crigler-Najjar Type 1 (CN-1) disorder have an unconjugated hyperbilirubinaemia due to the complete absence in activity of uridinediphosphate glucuronosyltransferase, a bilirubin-conjugating enzyme. In pregnant women with CN-1, the foetus is at high risk of being adversely affected by the bilirubin, as unconjugated bilirubin can cross the placenta and is potentially neurotoxic. We report the long-term outcomes of two infants born to women with CN-1. These infants had exchange transfusions soon after birth and have normal neurodevelopmental outcomes at 18 months and four years of age, respectively. We propose that this intervention might have improved the neurological outcome of these infants.

Ticagrelor--a new platelet aggregation inhibitor in patients with acute coronary syndromes. An improvement of other inhibitors?

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Clopidogrel, is a pro-drug that needs to be metabolized in the liver and intestines to form active metabolites. Prasugrel, a third generation thienopyridine, was approved for use in Europe in February 2009, and is currently available in the United Kingdom. All thienopyridines however, have pharmacological limitations that lead to a search for more effective non-thienopyridine P2Y12 inhibitors. Promising results have been reported with ticagrelor, an oral first reversible, direct-acting inhibitor of the P2Y12 receptor. Ticagrelor is the first oral P2Y12 receptor binding antagonist that does not require metabolic activation. Furthermore, ticagrelor has at last 1 active metabolite, which has very similar pharmacokinetics to the parent compound. Therefore, ticagrelor has more rapid onset and more pronounced platelet inhibition than other antiplatelet agents. The safety and efficacy of ticagrelor compared with clopidogrel in ACS patient has been recently evaluated by the PLATelet inhibition and patient Outcomes (PLATO) trial. Ticagrelor compared with clopidogrel had a significantly greater reduction in the death rate from vascular causes, myocardial infarction, or stroke without major bleeding. There was however, an increase in non-procedure related bleeding, dyspnoea and ventricular pauses in the first week of treatment. Further studies on new antiplatelet agents are needed to establish a new "gold standard" antiplatelet therapy.

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease.

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.

Sleeping position, oxygen saturation and lung volume in convalescent, prematurely born infants.

OBJECTIVE: To determine whether the effects of sleeping position on lung volume and oxygenation are influenced by postmenstrual age (PMA) and oxygen dependency in convalescent prematurely born infants. DESIGN: Prospective study. SETTING: Tertiary neonatal unit. PATIENTS: 41 infants (21 oxygen dependent), median gestational age 28 weeks (range 24-31 weeks) and birth weight 1120 g (range 556-1780 g). INTERVENTION: Infants were studied both supine and prone at two-weekly intervals from 32 weeks' PMA until discharge. Each posture was maintained for 1 h. MAIN OUTCOME MEASURES: Pulse oximeter oxygen saturation (Spo(2)) was monitored continuously, and at the end of each hourly period functional residual capacity (FRC) was measured. RESULTS: Overall, lung volumes were higher in the prone position throughout the study period; there was no significant effect of PMA on lung volumes. Overall, Spo(2) was higher in the prone position (p = 0.02), and the effect was significant in the oxygen-dependent infants (p = 0.03) (mean difference in Spo(2) between prone and supine was 1.02%, 95% CI 0.11% to 1.92%), but not in the non-oxygen-dependent infants. There was no significant influence of PMA on Spo(2). CONCLUSION: In the present study, prone sleeping did not improve oxygenation in prematurely born infants, 32 weeks' PMA or older and with no ongoing respiratory problems. However, the infants were monitored in each position for an hour, thus it is recommended that oxygen saturation should continue to be monitored after 32 weeks' PMA to be certain that longer periods of supine sleeping are not associated with loss of lung volume and hypoxaemia.

Antenatal smoking and substance-misuse, infant and newborn response to hypoxia.

OBJECTIVES: To determine at the peak age for sudden infant death syndrome (SIDS) the ventilatory response to hypoxia of infants whose mothers substance misused in pregnancy (SM infants), or smoked during pregnancy (S mothers) and controls whose mothers neither substance misused or smoked. In addition, we compared the ventilatory response to hypoxia during the neonatal period and peak age of SIDS. WORKING HYPOTHESIS: Infants of S or SM mothers compared to control infants would have a poorer ventilatory response to hypoxia at the peak age of SIDS. STUDY DESIGN: Prospective, observational study. PATIENT-SUBJECT SELECTION: Twelve S; 12 SM and 11 control infants were assessed at 6-12 weeks of age and in the neonatal period. METHODOLOGY: Changes in minute volume, oxygen saturation, heart rate, and end tidal carbon dioxide levels on switching from breathing room air to 15% oxygen were assessed. Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine, and benzodiazepines. RESULTS: The S and SM infants had a greater decline in minute volume (P = 0.037, P = 0.016, respectively) and oxygen saturation (P = 0.031) compared to controls. In all groups, the magnitude of decline in minute volume in response to hypoxia was higher in the neonatal period compared to at 6-12 weeks (P < 0.001). CONCLUSIONS: Both maternal substance misuse and smoking were associated with an impaired response to a hypoxic challenge at the peak age for SIDS. The hypoxic ventilatory decline was more marked in the neonatal period compared to the peak age for SIDS indicating a maturational effect. Pediatr Pulmonol. 2017;52:650-655. © 2016 Wiley Periodicals, Inc.

Prediction of infant extubation outcomes using the tension-time index.

OBJECTIVE: The tension-time index of the diaphragm (TTdi) is a composite assessment of the load on and the capacity of the diaphragm. TTmus is a non-invasive tension-time index of the respiratory muscles. Our aim was to determine whether TTdi or TTmus predicted extubation outcome and performed better than respiratory muscle strength (Pimax, Pdimax), respiratory drive (P0.1) and work of breathing (transdiaphragmatic pressure-time product (PTPdi)) or routinely available clinical data. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Sixty infants, median gestation age 35 (range 23-42) weeks and postnatal age of 55 (range 1-115) days. INTERVENTIONS: Airway occlusions were performed to measure Pimax, Pdimax and P0.1. TTdi and PTPdi were derived from measurements of transdiaphragmatic pressure. TTmus was derived from airway pressure measurements. Measurements were made within 6 h of extubation. MAIN OUTCOME MEASURES: Extubation failure defined as reintubation within 48 h of extubation. RESULTS: Twelve infants failed extubation. The infants who failed extubation were significantly more immature (medians 25 vs 37 weeks) and of greater postnatal age (23 vs 5 days) and had higher TTdi (0.15 vs 0.04) and TTmus (0.17 vs 0.08). TTdi and TTmus were only significantly better predictors than the peak inflation pressure immediately prior to extubation and did not perform significantly better than gestational age or birth weight. CONCLUSIONS: Assessment of TTdi and TTmus cannot be recommended for use in routine clinical practice.

Antenatal substance misuse and smoking and newborn hypoxic challenge response.

OBJECTIVES: Infants of smoking (S) and substance misusing (SM) mothers have an increased risk of sudden infant death syndrome. The aim of this study was to test the hypothesis that infants of SM or S mothers compared with infants of non-SM, non-smoking mothers (controls) would have a poorer ventilatory response to hypoxia, which was particularly marked in the SM infants. DESIGN: Physiological study. SETTING: Tertiary perinatal centre. PATIENTS: 21 SM; 21 S and 19 control infants. Infants were assessed before maternity/neonatal unit discharge. INTERVENTIONS: Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine and benzodiazepines. MAIN OUTCOME MEASURES: During quiet sleep, the infants were switched from breathing room air to 15% oxygen and changes in minute volume were assessed. RESULTS: The SM infants had a greater mean increase (p=0.028, p=0.034, respectively) and a greater magnitude of decline (p<0.001, p=0.018, respectively) in minute volume than the S infants and the controls. The rate of decline in minute volume was greater in the SM infants (p=0.008) and the S infants (p=0.011) compared with the controls. CONCLUSIONS: Antenatal substance misuse and smoking affect the infant's ventilatory response to a hypoxic challenge.

Crossover study of proportional assist versus assist control ventilation.

OBJECTIVE: To test the hypothesis that in very prematurely born infants remaining ventilated beyond the first week, proportional assist ventilation (PAV) compared with assist control ventilation (ACV) would be associated with reduced work of breathing, increased respiratory muscle strength and less ventilator-infant asynchrony which would be associated with improved oxygenation. DESIGN: Randomised crossover study. SETTING: Tertiary neonatal unit. PATIENTS: 12 infants with a median gestational age of 25 (range 24-26) weeks were studied at a median of 43 (range 8-86) days. INTERVENTIONS: Infants were studied for 1 h each on PAV and ACV in random order. MAIN OUTCOME MEASURES: At the end of each hour, the work of breathing (assessed by measuring the diaphragmatic pressure time product), thoracoabdominal asynchrony and respiratory muscle strength (maximal inspiratory pressure, maximal expiratory pressure (Pemax) and maximal transdiaphragmatic pressure (Pdimax)) were assessed. Blood gas analysis was performed and the oxygenation index (OI) calculated. RESULTS: After 1 h on PAV compared with 1 h on ACV, the median OI (5.55 (range 5-11) vs 10.10 (range 7-16), p=0.002) and PTP levels were lower (217 (range 59-556) cm H2O.s/min vs 309 (range 55-544) cm H2O.s/min, p=0.005), while Pdimax (44.26 (range 21-66) cm H2O vs 37.9 (range 19-45) cm H2O, p=0.002) and Pemax (25.6 (range 6.5-42) cm H2O vs 15.9 (range 3-35) cm H2O levels p=0.010) were higher. CONCLUSIONS: These results suggest that PAV compared with ACV may have physiological advantages for prematurely born infants who remain ventilated after the first week after birth.

Neonatal liver disease associated with placental transfer of anti-mitochondrial antibodies.

BACKGROUND: Anti-mitochondrial antibody is the diagnostic hallmark of primary biliary cirrhosis. Its role in the aetiology of primary biliary cirrhosis is controversial. METHODS: Two cases of neonatal hepatitis seropositive for anti-mitochondrial antibody are described. Anti-mitochondrial antibody Ig isotype and epitopic specificity were investigated by immunofluorescence and enzyme immunoassays. RESULTS: In both infants anti-mitochondrial antibody was of the G class, mainly G1 and G3 subclasses, and reacted with two synthetic peptides reproducing major M2 epitopicregions: innerlipoyl domain pyruvate dehydrogenase complex (PDC)-E2(162-176) and PDC-E3 binding protein (PDC-E3BP)86-100. One infant also reacted with outer lipoyl domain PDC-E2(35-49), and 2-oxoglutarate dehydrogenase complex (OGDC)-E2(99-113). An identical pattern of reactivity was present in their mothers, indicating the maternal origin of the antibodies. Anti-mitochondrial antibody disappeared in the infants with the disappearance of the liver pathology. CONCLUSIONS: The simultaneous disappearance of hepatitis and anti-mitochondrial antibody in the infants suggests a possible causal link between the two.

Nasal and lower airway levels of nitric oxide in prematurely born infants.

BACKGROUND: Nitric oxide (NO) is produced by various cells in the respiratory tract, but the majority is released from the paranasal sinuses in adults. The paranasal sinuses in infants are only partially pneumatised. Thus, nasal NO would be predicted to be low in infants measured soon after birth and/or born very prematurely; this has implications for the measurement of exhaled NO and interpretation of the results obtained. OBJECTIVES: To determine whether nasal NO could be detected in very immature infants, particularly soon after birth, and whether nasal or lower airway NO levels were influenced by gestational age or postnatal age. PATIENTS: Fifteen infants, with median gestational age of 27 weeks (range 25-32 weeks). METHODS: Nasal and lower airway NO measurements were attempted on days 1, 3, 5, 7, 14, 21, and 28 after birth. Measurements were only made while the infants remained ventilated. Nasal NO was sampled directly from the nasal space and lower airway. NO was sampled from a catheter positioned so that its tip lay at the lower end of the endotracheal tube. RESULTS: Nasal NO was detected in all infants on all study occasions and the levels were greater than those from the lower airway. Nasal and lower airway NO levels did not correlate significantly with gestational age, but lower airway NO levels correlated with postnatal age (r=0.86, p=0.014). CONCLUSION: Even in very immature infants examined in the first day after birth, care must be taken to avoid contamination with nasal NO, if lower airway levels are to be accurately assessed.

Influence of ventilatory settings and sampling position on measurements of simulated exhaled nitric oxide levels.

Chronic lung disease is a common adverse outcome of prematurely born infants and is associated with an early inflammatory response, which persists over weeks. As a consequence, it is possible that exhaled nitric oxide levels might be raised in affected infants. The majority of such infants will be ventilated in the first weeks of birth and thus it is important to determine the influence of mechanical ventilation on nitric oxide levels. As a consequence, our aim was to determine whether, during mechanical ventilation, simulated exhaled nitric oxide levels were influenced by changes in ventilator settings or the sampling catheter position. A lung model was created consisting of a rubber bag inside a 11 jar. An endotracheal tube (ETT) was fixed securely within the neck of the bag. Nitric oxide was delivered into the bag at a constant rate to simulate production and sampled from within the ETT and the bag. The sampled nitric oxide was analysed using a Sievers chemiluminescence analyser. The ETT was attached to a neonatal ventilator and a nitric oxide scavenger placed in the ventilator's inspiratory limb to ensure nitric oxide free gas was delivered. Comparison of different sampling positions revealed that the highest peak nitric oxide level within the ETT was at the tip. Increasing peak inflating pressure and ventilator rate resulted in a decrease in the peak nitric oxide levels. Increasing the inspired oxygen concentration also was associated with a reduction in the peak nitric oxide levels, the effect being more pronounced when larger volume lung models were examined. The results emphasized that the conditions of measurement must be standardized in infants receiving respiratory support, if exhaled nitric oxide results are to be appropriately interpreted.