Summer meeting of the Neonatal Society, 2002

Early Human Development (2005) 81, 205 — 224

www.elsevier.com/locate/earlhumdev

ABSTRACTS

Summer meeting of the Neonatal Society, 2002 Summer Meeting, Neonatal Society, Tours, France Friday 28th June 2002 08.00 — 08.55

Registration, coffee

08.55

Welcome Professor Elie Saliba and Dr Nikki Robertson

Chairman Dr Nikki Robertson 09.00

The effect of early nasal CPAP on lung function and injury in a primate model of BPD. MA Thomson

09.15

Does infection with Ureaplasma urealyticum result in a specific clinical and radiological pattern in the preterm infant? U Theilan (introduced by Dr AJ Lyon)

09.30

Prediction of chronic lung disease from chest radiograph appearance at 7 days of age. A Greenough

09.45

Oxygen monitoring: too low or too high? National survey of oxygen saturation monitoring policies and the audit of the effect of change of policy in a single Neonatal Intensive Care Unit (NICU). C Lacamp (introduced by Dr W Tin)

10.00

First year morbidity among infants discharged home in oxygen. NJ Shaw

10.15

Relative risks of Respiratory syncytial virus (RSV) hospitalisation in the first 2 years of life in premature infants with and without neonatal respiratory illness. R Thwaites

10.30 — 11.00

Coffee

Chairman Professor Terence Stephenson 11.00

Young Investigator Prize Lecture Dr Helen Budge Academic Division of Child Health Nottingham, UK dProgramming of fetal adipose tissue development by maternal nutrition and prolactin.T

11.45

Changes in plasma cortisol with ventilation and analgesia in preterm infants. CM Wong (introduced by Dr I Laing)

12.00

Blood concentration of amethocaine and its metabolite after topical application. A Jain

12.15

Apnoea and periodic breathing. A Hassan

12.30 — 14.00

Lunch

doi:10.1016/j.earlhumdev.2004.11.001

206

Abstracts

Chairman Dr Paul Johnson 14.00

The 6th annual Tizard Lecture Professor Petra Huppi Director of Child Development Unit University Hospitals of Geneva Switzerland dSteroids and the developing brain — what have magnetic resonance techniques taught us?T

15.00

Secondary energy failure in a neonatal rat brain slice model. NJ Robertson

15.15

Brain natriuretic peptide concentrations predict haemodynamically significant patent ductus arteriosus in preterm infants. VF Puddy (Introduced by Dr S Calvert)

15.30 — 16.00

Tea

Chairman Dr Andrew Lyon 16.00

Increased sodium absorption across the nasal epithelium of ventilated moderately preterm infants on the first day of postnatal life. EA Gaillard

16.15

Effect of posture on oxygenation and respiratory function in prematurely born infants studied prior to discharge. RY Bhat

16.30

The effect of maternal dietary supplementation in late gestation on the behavioural development of the neonatal pig. JC Litten

16.45

Proportional assist ventilationin vitro assessment of the effect of unloading on ventilator performance. JA Leipa ¨la ¨

17.00

Reversibility of n-3 polyunsaturated fatty acids (n-3 PUFA) diet deficiency-induced alterations of dopaminergic neurotransmission: critical role of developmental stage. E Kodas

17.15

End of session

19.15

Coaches leave for Neonatal Society Dinner in Chinon

Saturday 29th June 2002 Chairman Professor Anne Greenough 09.30

Computerised breath sounds analysis in term and preterm infants. A Majumdar

09.45

Impaired splanchnic haemodynamic responses to enteral feeding in preterm growth restricted infants. EM Murdoch

10.00

Differential regulation of subcutaneous and visceral adipose tissue mass in early infancy. Modi N

10.15

The effects of maternal dietary fat supplement during late gestation on the growth performance and endocrine profile of the neonatal pig. KS Perkins

10.30

Effect of maternal nutrient restriction during late-gestation on hepatic prolactin receptor (PRLR) abundance in neonatal lambs. T Stephenson

10.45

Evaluation of Advanced Neonatal Nurse Practitioners: Confidential enquiry into the management of sentinel cases. MP Ward Platt

11.00

Scoring for the future: SNAPE-II works in Wessex. K Turnock (introduced by Dr R Thwaites)

11.15

Nursing workload by dependency category of baby in a tertiary neonatal intensive care setting. DWA Milligan

11.30 — 12.00

Coffee

Neonatal Society Abstracts

207

Chairman Professor Elie Saliba 12.00

State of the art lecture Professor Pierre Gressens Laboratoire de Neurologie du De ´veloppement INSERM E9935 Ho ˆpital Robert Debre Paris, France dNeuroprotection in the newborn brain — interactions between stress, glutamate and glucocorticoids.T

13.00 — 14.00

Lunch

14.00

End of Scientific session

14.30 — 18.00

Optional tour of surrounding Chateaux

Impaired response to tube breathing in infants born to smoking mothers Bhat RY, Broughton S, Hannam S, Rafferty GF, Milner AD, Greenough A. Dept of Child Health, Guy’s, King’s and St Thomas’ Medical School, London, UK Background: Infants of smoking mothers have an increased risk of sudden infant death, a possible mechanism being reduced drive to breathe (1). We have previously demonstrated that newborns are able to compensate fully for an imposed physiological dead space (tube breathing) by increasing their minute ventilation (2).

age of 39 (37—42) weeks and 41 (38—42) weeks, respectively) and (median postnatal age of 42(22— 53) h and 26(20—44) h, respectively) were studied. Results: The median MMV achieved by the two groups was similar [442 (262—631) ml/min/kg versus 395(192—518) ml/min/kg, p=0.4]. The infants of smoking mothers, however, took longer to achieve 63% of the MMV [37.3 (27—70.2) s versus 29 (22.7— 41.9) s, p=0.045]. Conclusion: The impaired response to tube breathing suggests intrauterine exposure to tobacco smoke dampens chemoreceptor response. References

Objective: To test the hypothesis that infants of smoking mothers would have an impaired response to tube breathing. Methods: A face mask was placed over the infant’s face. Flow was recorded from a pneumotachograph, which was connected to face mask by a wide bore tube. The flow signal was integrated to give volume and the breath to breath minute volume calculated. A three way tap was connected to the pneumotachograph by a second wide bore tube. When the threeway tap was in the neutral position, a 2 L/min flow of gas passed directly to the face mask. When the three-way tap was rotated, the flow was redirected down the side arm of the system and a dead space of 4.4 ml/kg was incorporated into the circuit without having to remove the face mask. The infant breathed through the dead space for 2 min. The breath by breath minute ventilation was plotted against time (seconds) and a polynomial regression line was drawn through the data points. The maximum minute ventilation (MMV) was recorded and the time taken to achieve 63% of the MMV calculated. Patients: Ten infants of smoking mothers and 10 infants of non-smoking mothers (median gestational

[1] Ueda Y, Stick SM, Hall G, Sly PD. Control of breathing in infants born to smoking mothers. J Pediatr 1999;135:226—32. [2] Upton CJ, Milner AD, et al. Dynamic response to tube breathing during the first 10 days of life. Paediatr Pulmonol 1990;9:72—9. Increased sodium absorption across the nasal epithelium of ventilated moderately preterm infants on the first day of postnatal life Gaillard EA, Shaw NJ, Wallace HL*, Subhedar NV, and Southern KW* Liverpool Women’s Hospital, Neonatal Unit, Crown Street, Liverpool L8 7SS, UK *Institute of Child Health, University of Liverpool, UK Aims: To examine through the nasal potential difference (PD) profile, airway ion transport in moderately preterm infants (from 29 weeks gestation). Background: Despite recent advances, lung disease following premature birth remains a significant clinical problem. Animal and clinical studies suggest

208

Abstracts

that airway ion transport has a critical role in the adaptation to air breathing in postnatal life. In particular, sodium absorption mediated through the epithelial sodium channel (ENaC) is a major factor in lung water clearance after birth.(1) The a-ENaC subunit m-RNA expression has been found to increase with gestational age.(2) Immature airway ion transport as a result of prematurity may therefore contribute to the respiratory morbidity in infants born moderately preterm.

state after birth in this cohort, similar to term infants. We found increased nasal PD in some ventilated preterm infants after birth. Damil in these infants confirms that the increased PD principally reflects ENaC-mediated sodium absorption. The sodium hyperabsorption evident in some of the ventilated preterm infants may reflect a compensatory mechanism to clear fluid from the lungs. References

Methods: We studied 75 infants using a modified perfusion protocol suitable for neonates (healthy term infants n=40; preterm 29—36 weeks gestation n=35). We determined: (1) (2)

(3)

Maximal baseline PD following perfusion of a physiological isotonic solution. The change in PD following perfusion with amiloride 10
4 M (Damil, to assess ENaC activity). The change in PD, after perfusion with a solution low in Cl
(to assess the capacity for Cl
secretion).

Results: Maximal baseline PDs are shown in graph 1. Four ventilated infants had maximal baseline PDs greater than
50 mV. Amiloride perfusion resulted in substantial reduction in PD magnitude (median Damil in pretem, 80%) and there was little capacity for chloride secretion in either cohort. Conclusion: This is the first reported clinical study examining the postnatal airway ion transport pattern in moderately preterm infants and these data suggest these processes are well developed in these infants on day 1 of postnatal life. The findings support a normal switch from the fetal secretory pattern to a fluid absorptive

[1] Hummler E, Barker P, Gatzy J, Beermann F, Verdumo C, Schmidt A, Boucher R, Rossier BC. Nature Genetics 1996;12:325—8. [2] Tchepichev S, Ueda J, Canessa C, Rossier BC, O’Brodovich H. American Journal of Physiology 1995;269:C805—12. Prediction of chronic lung disease from the chest radiograph appearance at 7 days of age A Greenough, M Thomas, A Johnson*, J Peacock*, N Marlow#, S Calvert* Departments of Child Health, King’s College Hospital, *St George’s Hospital Medical Schools, London and #University Hospital, Nottingham, UK Background: Chronic lung disease (CLD) occurs in more than 50% of infants born below 29 weeks of gestation and is associated with significant mortality and morbidity. Although, systemic administration of corticosteroids in the second week after birth can reduce the development of CLD and improve survival, this treatment may have longterm adverse effects. It is, therefore, important only to treat those infants at highest risk of CLD. Aim: To determine whether the chest radiograph (CXR) appearance at 7 days predicted CLD develop-

Neonatal Society Abstracts ment and was a better predictor than readily available clinical data. Patients: Fifty-nine infants with a median gestational age of 26+1 weeks (range 24+0 to 28+5) and birthweight 768 g (528 to 1097) entered into the UKOS study and cared for at King’s College or St George’s Hospitals. Methods: Chest radiographs taken at 7 days were assessed using a scoring system for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation. Data were collected regarding gestational age, birthweight, use of antenatal steroids and postnatal surfactant and each infant’s oxygenation index was calculated at 120 h. Results: Thirty-nine infants developed CLD (oxygen dependency at 36 weeks PMA). Compared to the rest of the cohort, the CLD infants were not significantly more immature, but had a lower birthweight ( p=0.03) and had a higher total CXR score ( p=0.0003), with higher scores for fibrosis/interstitial shadowing ( p=0.0002). Construction of receiver operator characteristic (ROC) curves revealed that the total CXR score compared to the clinical data had the highest area under the ROC curve (0.88) with regard to prediction of CLD. A CXR score greater than 3 had 85% sensitivity and 78% specificity in predicting CLD. Conclusion: These results suggest the CXR appearance at 7 days is an accurate predictor of CLD development in very immature infants. Apnoea and periodic breathing Akbar Hassan, Dorothea Ingram and Anthony Milner Dept of Child Health, Guy’s, King’s and St Thomas’ Hospitals, King’s College, London Background: Apnoea occurring in association with periodic breathing (Periodic Apnoea, PA) is of interest as it represents cessation of breathing due to instability of respiratory control rather than just central suppression of breathing or reduction in chemoreceptor drive. Aims: To assess the frequency of PA, how it related to the cycle time of the periodic breathing and how the pattern of PA changed with increasing age in preterm infants. Methods: Twenty-six preterm infants (mean gestation: 29+4, range 25+1 to 32) were studied on 76 occasions, with approximately 1 week between studies. The infants were studied over 4-h periods.

209 Nasal airflow (thermistor), abdominal wall movement (Respitrace), saturation and heart rate (pulse oximeter) were recorded using a magnetic tape recorder. Apnoeas lasting at least 5 s were identified and classified. The cycle time for periodic breathing was obtained by measuring the time from one nadir to the next. Results: 5875 apnoeas were identified. Of these, 67.4% occurred in association with periodic breathing (93.2% central, 6.1% mixed and 0.7% obstructive). The length of these apnoeas was directly proportional to the cycle time of the periodic breathing ( pb0.001). The mean cycle time fell from 17.2 s at day 5 to 12.5 s at day 85 ( pb0.01). Unlike isolated apnoeic attacks, PA increased with age, both for Pas greater than 10 s ( pb0.05) and for Pas lasting 5 to 10 s ( pb0.05). Conclusion: Apnoea associated with periodic breathing accounted for 2/3 of all apnoea of prematurity. There was a significant relationship between the periodic breathing cycle and the length of these apnoeas. The increasing incidence of PA with age indicates an increasing instability, i.e. less dampening of respiratory control. Blood concentration of amethocaine and its metabolite after topical application Anoo Jain1, Nick Rutter1, John Gilmer2 1 Department of Neonatal Medicine, City Hospital, Nottingham, 2Department of Pharmaceutical Chemistry, Trinity College, Dublin Background: Topical amethocaine provides effective pain relief during venepuncture in the newborn infant1. Little is known about its metaboism or safety following application in this age group. Aim: To investigate the blood concentration of amethocaine and its metabolite p-butylamino benzoic acid (BABA) following topical application in the newborn infant. Design: Analysis of samples from a randomised placebo controlled trial. Subjects: 44 newborn infants, gestation 27 to 41 weeks (median 33), age 2 to 17 days (median 7), undergoing routine venepuncture. Method: 1.5 g of 4% w/w amethocaine gel or placebo was applied to the skin under occlusion for 1 h, then wiped away. Venepuncture was performed 5 min later. An additional 0.5 ml of blood was collected into a sample bottle containing 0.5 ml of HPLC grade acetonitrile and placed don iceT. Within

210 15 min the sample was centrifuged and then stored at
20 8C. The samples were analysed by high pressure liquid chromatography. The analytical limit was 50 ng/ml for amethocaine and BABA. Results: 19 samples were taken following the application of amethocaine. In 7 out of 19 the concentration of amethocaine was b50 ng/ml. In the remainder the concentration ranged from 69.9 to 3345.6 ng/ml. The concentration of BABA was b50 ng/ml in 16 out of 19 samples and 75, 75 and 88 ng/ml, respectively, in the remaining three. Eight of the 11 samples with a high amethocaine concentration had a corresponding BABA concentration of b50 ng/ml. In two out of three samples where blood was taken from a site distant to the site of application, the concentration of amethocaine was b50 ng/ml. No local or systemic adverse reactions were noted. Conclusion: Following the application of topical amethocaine gel for 1 h the concentration of BABA is below or close to the level of quantification. The pattern of a high amethocaine concentration paired with a low BABA concentration in some samples suggests contamination with amethocaine at venepuncture. This data supports the use of topical amethocaine gel prior to invasive procedures in the newborn infant. References [1] Jain A, Rutter N, Does topical amethocaine gel reduce the pain of venepuncture in newborn infants? A randomised double blind controlled trial. Arch Dis Child 2000;83:F207. Reversibility of n-3 polyunsaturated fatty acids (n-3 PUFA) diet deficiency-induced alterations of dopaminergic neurotransmission: critical role of developmental stage Kodas E., Vancassel S*., Guilloteau D and Chalon S. INSERM U316, Laboratoire de Biophysique Me ´dicale et Pharmaceutique, Universite ´ Franc¸ois Rabelais, 31, Avenue Monge, 37200 Tours, France, E-mail: [email protected] * LNSA, INRA Jouy-en-Josas. Synaptogenesis and neurogenesis require high incorporation of n-3 PUFAs in cerebral membranes during the perinatal period. The precise need of these essential PUFAs for optimal brain function can be clarified through animal models. In rodents, chronic n-3 PUFA deficiency affects the fatty acid (FA) composition of cerebral membranes and

Abstracts impairs performances in learning and behavioural tasks. As these tasks are under the dependence of monoaminergic neurotransmission systems, we suggested that this deficiency could disturbed their regulation. Our recent investigations showed altered FA composition and abnormal functioning of the mesocortico-limbic dopaminergic pathway in this model. The aim of this study was therefore to determine (i) whether these biochemical and neurochemical modifications could be reversed by normalising n-3 PUFA supply in deficient animals, (ii) if this reversibility could occur whatever the stage of life at which the regimen was shifted. Reversal diet has been supplied to deficient rats at birth, 7, 14 or 21 days of age (group D0, D7, D14, D21). At the adulthood, we determined in the prefrontal cortex and nucleus accumbens (i) the FA composition of neuronal phospholipids and (ii) the level of stimulated dopamine release using dual-probe microdialysis technique. The recovery of FA composition was complete for all dietary groups. For D0, D7 and D14 groups, the level of stimulated dopamine release was identical to controls, whereas it was similar to deficient group for D21. The shift of n-3 PUFA deficient diet to a normal diet allowed biochemical brain recovery whatever the stage of repletion, whereas restoration of dopaminergic function was dependent of the developmental stage of repletion. This suggested that neurochemical function could not be directly related to biochemical composition of neuronal membranes. The degree of brain maturation seems play a critical role in the ability to recover neurochemical functions altered by n-3 PUFA deficiency. Oxygen monitoring: too low or too high? National survey of oxygen saturation monitoring policies and the audit on the effect of change of policy in a single Neonatal Intensive Care Unit (NICU) Lacamp C and Walker S (Introduced by Dr. W. Tin) Department of Paediatrics, The James Cook University Hospital, Middlesbrough TS4 3BW, UK Background: Pulse oximetry has been widely used for monitoring saturation in babies needing supplemental oxygen, but uncertainty remains as to most appropriate target range in the very preterm baby. The prospective observational study published recently concluded that the attempts to keep oxygen saturation at so-called bphysiologicalQ level may do more harm than good in babies of less than 28 weeks gestation1. Aim: (1) To find out how much oxygen saturation monitoring policies vary amongst NICUs in the

Neonatal Society Abstracts United Kingdom, and (2) To look at the effect of change in policy from bhighQ to blowQ saturation limits in one NICU. Methods: (1) A telephone questionnaire survey of all NICUs with three or more intensive care cots, caring for babies of under 28 weeks gestation in the UK using NICU directory. (2) A review of the records of all babies in one unit, who survived infancy after delivery between 25 and 27 weeks gestation in 1995 and 96 (high limits) and 1998 to 2000 (low limits). Results: (1) Out of 104 NICUs surveyed, a response was obtained from 100 units (response rate 96%). Forty two of 100 NICUs set their lower alarm limit for a saturation at 90% or higher, and 38 units set their upper limit at 98% or higher. Ninety percent set the lower limit between 85% and 93% and the upper limit between 93% and 99%. Only two units let saturation vary 15% or more; 19 units let it vary 6% or less. (2) There were 52 babies cared for with high oxygen saturation limits (88—98%), and 67 with low limits (75—93%). Birth weight, gender and antenatal steroid uptakes were comparable in the two groups. There was no difference in 1 year survival (71% in 1995—1996 vs. 79% in 1998—2000), but babies cared for using a restricted oxygen policy required only half as much ventilatory support (median 5 vs. 13 days, mean 9.8 vs. 16.4 days). Conclusions: There is no consensus in the UK over how to monitor oxygen saturation in the very preterm baby. Accepting a saturation limit of 75— 93% is associated with much shorter period of ventilatory support. References [1] Tin W, Milligan DWA, Pennefather PM, Hey E. Arch Dis Child 2001;84:F106—10. Proportional Assist Ventilation—in vitro assessment of the effect of unloading on ventilator performance Jaana A Leipa ¨la ¨, Shiho Iwasaki, Anthony Milner, Anne Greenough Children Nationwide Neonatal Intensive Care Centre, King’s College Hospital, London, UK Background: During proportional assist ventilation (PAV) the applied pressure is servo controlled throughout each spontaneous breath. The applied pressure increases in proportion to the flow and tidal volume generated by the patient, which

211 enhances the effect of the patient’s respiratory efforts on ventilation. The clinician can vary the degree of enhancement or bunloadingQ. Resistive unloading relieves the resistive work of breathing and elastic unloading the elastic work of breathing (1). Excessive unloading, however, could result in brunawayQ ventilator pressures or oscillations (2). Aim: To evaluate varying levels of unloading during PAV on ventilator performance, using a lung model simulating RDS. Methods: A Stephanie ventilator was connected via a pneumotachograph and size three endotracheal tube to a 1-l bottle (compliance 0.79 ml/cmH2O and resistance 87 cmH2O/l/s). The flow signal from the pneumotachograph and attached differential pressure transducer was integrated to give volume. Airway pressure was measured from a side-port on the pneumotachograph. Flow, volume and pressure were simultaneously recorded on a Gould polygraph. A 20 ml syringe was attached to a separate inlet into the bottle and was used to simulate spontaneous breaths. Volumes of 5, 10, 15 and 20 ml were withdrawn from the lung model simulating inspiration. At each setting the results of five breaths were meaned. The ventilator was set to CPAP and PAV mode and varying levels of elastic (0.25—4.0 cmH 2 O/ml) and resistive (25—200 cmH2O/l/s) unloading were studied. The experiments were then repeated with pressure limits of 20, 30, 40 and 50 cmH2O. Results: At a resistive unloading of 50 cmH2O/l/s or greater oscillations appeared, indicating resistive overcompensation. Pressures of greater than 40 cmH2O were observed when inspiratory volumes of 20 ml were used with an elastic unloading of 0.75 cmH2O/ml or greater and with volumes of 10 ml or more when the elastic unloading was 1.0 cmH2O/ml or greater. Limiting the peak pressure to 20 cmH2O resulted in short inflation times (Tib0.2 s) when an elastic unloading of 0.75 cmH2O/ml or greater was employed. Conclusion: The degree of unloading is crucial to appropriate delivery of PAV, this will vary according to the infant’s underlying lung disease. References [1] Schulze A Schaller P. Assisted mechanical ventilation using resistive and elastic unloading. Seminars in Neonatology 1997;2:105—14. [2] Schulze A, Rich W, Schellenberg L et al. Effects of different gain settings during assisted

212

Abstracts

mechanical ventilation using respiratory unloading in rabbits. Pediatric Research 1998; 44:132—8. The effect of maternal dietary supplementation in late gestation on the behavioural development of the neonatal pig J.C. Litten, K.S. Perkins and L. Clarke Department of Agricultural Sciences, Imperial College at Wye, University of London, Wye, Ashford, Kent, TN25 5AH, UK Introduction: Body shape has been shown to influence both the physical and behavioural development of the neonatal piglet (1). Dietary fat supplementation to the sows in late gestation increased both piglet weight gain and piglet survival (2). Supplementation of infant formula has been shown to increase the mental development of the human neonate (3). Due to similar brain physiology, the piglet is analogous to the human for studies of early postnatal neural development (4). The objective was to determine whether maternal dietary supplementation influenced the physical and behavioural development of differently shaped pigs. Methods: Thirty-nine pregnant sows were randomly allocated to 5 dietary treatments as follows: standard diet (S: 3 kg of Pigbreed Pioneer Pellets, BOCM: 12.4 MJ/kg, 3% fat) or the standard diet plus 30% extra energy derived from either excess pellets (E), palm oil (PO), soya oil (SO or a 50:50 mixture of palm and soya oil (M). Sows were allowed to give birth naturally at term (115 days) and physical development was assessed by weekly measurements of piglet body weight and crownto-rump length (CRL) until weaning at 24—28 days. Piglet response to, and interaction with a ball for 1800 s on day 14 of neonatal life was used to calculate a numerical index of behavioural development as follows: Behavioural developmental index ðBDIÞ ¼ ð1800
Ttime Þ þ ð1800
Mtime Þ:

Table 1

T time=time taken to touch the ball (s) and M time= time taken to move the ball (s). Piglets were subdivided into three groups based on ponderal index (PI: body weight/CRL3: kg/m3): LOW (b10th percentile), NORMAL (11th—89th percentile) and HIGH (N90th percentile). General Linear Model and One way, ANOVA, were used to assess differences between each treatment groups. Results: Increased energy supplementation significantly influenced the behavioural development of the piglets ( Pb0.01) but the degree of improvement was dependent on their body shape at birth (Table 1). In the LOW group, BDI was enhanced only in the E group ( Pb0.05). An improvement in BDI was also observed in NORMAL piglets born to sows fed the E, PO and SO diets ( Pb0.05) but this was not shown in M group. Conversely, BDI was similar, irrespective of dietary treatment in the HIGH group. Treatment did not affect growth rate in the NORMAL or HIGH groups but it did influence growth rate in the LOW group. Conclusion: In conclusion, dietary supplementation of additional energy to sows during late gestation significantly improved BDI of LOW and NORMAL neonatal pigs. This effect appears to be due to the addition of extra energy from a number of different sources rather than to fatty acid supplementation as previously described by other authors (3). Acknowledgements: This work is partly funded by DEFRA. J.C.L. also wishes to thank Wye College for the provision of a PhD studentship. References [1] Litten JC, Corson AM, Drury PC, Clarke L. Early Human Development 2001;66:57—8. [2] Cieslak DG, Leibbrandt VD, Benevenga NJ. Journal of Animal Science 1983;57:955—9. [3] Birch EE, Garfield S, Hoffman DR, Uauy R. Developmental Medicine and Child Neurology 2000;42:174—81. [4] Purvis JM, Clandinin T, Hacker RR. Comparative Biochemistry and Physiology 1982;72B: 195—9.

Behavioural Developmental Index for each treatment and PI group

LOW (b10th) NORMAL (11—89th) HIGH (N90th) Values are meansFS.E.M.

S

E

PO

SO

M

1795F535 1921F222 1869F538

2789F434 2476F214 1750F520

2674F438 2335F190 2501F546

2548F658 2786F192 1859F589

1793F587 2071F223 2297F508

Neonatal Society Abstracts

213

Computerised breath sounds analysis in term and preterm infants

Nursing workload by dependency category of baby in a tertiary neonatal intensive care setting

A Majumdar, HE Elphick, NJ Shaw Liverpool Regional Neonatal Unit, Crown Street, Liverpool L8 7SS, UK

Milligan DWA, Wooler L, Ward Platt MP, Gibbs A, Mackley B, Carruthers P Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle upon Tyne, UK

Background and aims: Computerized breath sounds analysis provides a non-invasive method for objective assessment of lung sounds in infants. This pilot study aimed to investigate the normal breath sounds of term and preterm infants. Methods: Respiratory sounds were recorded using a contact sensor placed over the right upper zone of the infant’s chest, anteriorly. Air flow at the mouth was simultaneously recorded using a pneumotachograph. The recording on each occasion lasted for1 min of tidal breathing, with the baby quiet or asleep. Specialized equipment for sound recording and analysis was used (Respiratory Acoustics Laboratory Environment, RALE). The sound was analyzed using a Fast Fourier Transformation technique. At inspiratory flow rates of 0.1F20% l/s/kg, recordings were analyzed for each infant. The slope of the straight part of the plot of the log frequency against log intensity was calculated, as a measure of the overall breath sounds intensity. Results: Breath sounds intensity was higher at the same frequency in preterm infants compared to term infants and this was associated with gestational age (R 2=0.19). The average slope of the log frequency-log intensity distribution, was
3.4 in term infants and
3.8 in preterm infants ( pb0.05). Conclusions: Breath sounds intensity (loudness) was found to be higher in preterm compared to term infants. This may reflect that the relative size of the airways and the relative depth of chest wall cavity are important factors in determining breath sounds intensity. These data may provide a normal reference in order to study further neonates requiring oxygen and with chronic lung disease. References [1] Pasterkamp H, et al. Med Instrum 1983;17(5): 355—7. [2] Pasterkamp H, et al. Am J Respir Crit Care Med 1996;154:424—30. [3] Blowes RW, Milner AD, et al. Pediatr Pulmonol 1995;19:348—54.

Introduction: There is only one published study which has assessed the time spent by neonatal nurses caring for babies with a range of conditions. Since then both case mix and clinical practice have changed. This study examined neonatal nursing dependency in the context of current practice. Aims: For each system of categorising care: to re-examine that of the Northern Region, to validate that of the British Association for Perinatal Medicine as recently revised, and to evaluate the Nottingham scoring system proposed by Gibbs. Methods: We performed activity sampling analysis of nursing activity by trained observers at 10 min intervals for three 12 h day shifts and one 12 h night shift. We coded work using a taxonomy of nursing activities. The grades of nurse and the dimensions making up each of the category systems were recorded. Results: Between 27 and 30 babies were observed on each shift. Sufficient nursing capacity was available to allow all babies to receive the care they needed. No babies scored at the highest level of the Nottingham system. Babies receiving dnormalT baby care took similar amounts of nursing time to those receiving dspecial careT, and are counted together in the analysis below. Units are min/baby/h. BAPM

Northern

1 2

50.6 31.5

3

20.3

A (Vent) A (nCPAP) B C/D

Notts

55.6 30.4 30.3 21.0

E

N/A

I H

60.2 37.9

S

21.2

Conclusions: A three category scale provided an adequate functional description of neonatal unit workload. Babies on nasal continuous positive airways pressure support (nCPAP) required nursing time equivalent to the BAPM high dependency category or Northern Region category B, but babies at the highest level of intensive care occupied the full attention of a single nurse. Fully orally fed

214

Abstracts

babies needed similar nursing input to those in low dependency (special) care. References [1] Arch Dis Child 1993;68:534—38. [2] Arch Dis Child 1993;68:539—43. Differential regulation of subcutaneous and visceral adipose tissue mass in early infancy Harrington TAM1, Thomas EL2, Modi N1, Frost G3, Bell JD2 1 Section of Paediatrics and Neonatal Medicine, Imperial College Faculty of Medicine, 2Robert Steiner MR Unit, MRC Clinical Sciences Centre, 3 Department of Dietetics, Hammersmith Hospital, London, UK Background: In adults the regulation of adiposity is of interest as the quantity and distribution of adipose tissue (AT) are related to later morbidity. An increasing body of largely epidemiological data shows that infants who were small and thin at birth have an increased prevalence in adult life of biological risk factors strongly associated with visceral adiposity. Little is known about the regulation of AT mass deposition in early life. Aim: The aim of this study was to compare total and differential AT distribution at birth and at 6 weeks of age in full term appropriately grown (AG) and growth restricted (GR) infants. Methods: Infants were classified as GR if they had evidence of deceleration in growth in utero, clinical signs at birth suggestive of fetal malnutrition and a birth weight below the 10th centile. Total AT mass and regional (subcutaneous, visceral, other internal) AT distribution were assessed by magnetic resonance imaging using a technique we have developed for application to infants (Harrington et al., 2002). The study was approved by the institutional Research Ethics Committee. Written informed parental consent was obtained. Total and regional AT were compared birth and at 6 weeks of age in AG and GR Table 1 Total and regional AT mass as a percentage of body weight at birth %

GR (n=10)

AG (n=25)

P

Total AT mass Subcutaneous Visceral Other internal

17.53 16.13 0.42 1.14

23.4 21.44 0.61 1.35

b0.001 0.001 0.306 0.116

(2.11) (2.20) (0.22) (0.24)

(3.85) (3.81) (0.31) (0.34)

Table 2 Total and regional AT mass as a percentage of body weight at 6 weeks %

GR (n=8)

AG (n=21)

P

Total AT mass Subcutaneous Visceral Other internal

24.72 22.90 0.52 1.31

28.35 26.04 0.67 1.64

0.112 0.160 0.158 0.046

(5.25) (4.98) (0.25) (0.33)

(4.65) (4.58) (0.24) (0.41)

infants using multiple regression analysis allowing for postmenstrual age at imaging. Data are presented as mean (S.D.). Results: GR infant had a significantly reduced AT content at birth compared to AG infants. This difference arose from a reduction in subcutaneous AT, but not visceral or other internal AT (Table 1). There was a rapid increase in subcutaneous AT mass so that by 6 weeks of age there was no longer a difference between AG and GR infants (Table 2). In contrast, the content of visceral and other internal AT mass remained essentially unchanged. Conclusions: MRI adipose tissue imaging confirms that subcutaneous AT is reduced in the GR neonate at birth but also demonstrates that visceral AT mass is preserved. By 6 weeks GR infants have preferentially accumulated subcutaneous, but not visceral AT. We conclude that subcutaneous AT and visceral AT are under different regulatory control in early infancy. References [1] Harrington TA, Thomas EL, Modi N, et al. Lipids 2002;37:95—100. Impaired splanchnic haemodynamic responses to enteral feeding in preterm growth restricted infants Murdoch EM, Sinha AK, Kempley ST Department of Child Health, Queen Mary University of London, UK Neonatal Unit, Royal London Hospital E1 1BB, UK Background: In preterm infants, the first enteral feed results in an increase in superior mesenteric artery (SMA) blood flow velocity (1). Although smallfor-gestational-age (SGA) preterm infants have reduced SMA velocity on the first day of life (2), their response to enteral feeding is not known. Aim: To compare the splanchnic haemodynamic response to the first feed in preterm SGA and appropriately grown (AGA) preterm infants.

Neonatal Society Abstracts

215

Methods: Preterm infants admitted to the neonatal unit were defined as SGA if their birthweight was b2nd centile, or b9th centile with evidence of fetal blood flow redistribution. Blood flow velocity was measured from the superior mesenteric artery and coeliac axis (CA), using Doppler ultrasound. The time averaged mean velocity and pulsatility index (PI) was obtained from 5 consecutive arterial waveforms. Measurements were taken on the first day of life, then repeated before and after a standardised first enteral feed. First day measurements were compared using Students t-test; feeding studies were analysed using ANOVA. Results: Values are means (S.D.). Difference between SGA (*pb0.05, ***pb0.001)

Gestation (weeks) Birth weight (kg) Day 1 SMA velocity (cm/s) Prefeed SMA velocity 60 min post-feed SMA velocity Day 1 CA velocity (cm/s) Prefeed CA velocity 60 min post-feed CA velocity

SGA (n=20)

AGA (n=63)

32.2 1.15 15.0 27.0 27.8 30.9 35.7 34.2

29.3 1.39 25.8 26.2 31.7 38.8 44.4 44.6

(2.5)*** (0.34)* (6.6)*** (8.2) (9.2)* (8.6)* (11.9)* (11.7)*

(3.3) (0.50) (8.0) (6.8) (10.2) (16.3) (18.6) (12.9)

The SMA and CA velocity were reduced on the first day in SGA infants. Baseline SMA velocity at the time of the first feed was similar in both groups, but only AGA infants demonstrated a rise in SMA velocity following feeding. Coeliac velocity remained lower in the SGA group throughout and was unaffected by feeding.

Introduction: Early nutrition of the neonatal pig has a major impact on its survival and subsequent development (1). The objective of the study was to investigate the effects of maternal dietary supplementation during late gestation on the growth performance and endocrine profile of the neonatal pig. Methods: Twenty-one pregnant sows were randomly allocated to three treatment groups. They were offered either the standard diet (S: 3 kg of Pigbreed Pioneer Pellets, BOCM: 12.4 MJ/kg, 3% fat) or the standard diet plus 30% extra energy derived from either excess pellets (E) or palm oil (PO) from day 85 of gestation. Following parturition, piglets were reared with their mother but had access to a separate creep area; piglets were cross-fostered to equalise the litter size. During the period of lactation (0—28 days), sows were fed 3—9 kg/day concentrate (Pigbreed Ultimate Pellets, BOCM: 13.6 MJ/kg, 6% fat). Individual piglet body weight was measured within 24 h of birth and at 7, 14 and 21 days of neonatal life. A blood sample was taken from two piglets per litter on days 3 and 21 of life and analysed for plasma concentrations of glucose, thyroid hormones (T3 and T4) using RIA and insulin by ELISA. A General Linear Model, ANOVA, was used to assess differences between the groups.

The effects of maternal dietary supplementation during late gestation on the growth performance and endocrine profile of the neonatal pig

Results: Supplementing the maternal diet with excess pellets increased ( Pb0.05) average piglet birth weight (S 1.77F0.05: E 1.87F0.04: PO 1.62F0.04: kg, meanFS.E.M.), whereas palm oil decreased it ( Pb0.01). Growth rate over the first 3 weeks of life was only enhanced ( Pb0.01) in the E group (S 287F14: E 343F15: PO 275F25: g/day). Plasma glucose concentration was elevated ( Pb0.05) at 3 days of life only in the PO group (Table 1). Supplementing the maternal diet with extra energy during the last month of pregnancy resulted in higher circulating concentrations of thyroid hormones ( Pb0.05) on day 3 of life. By day 21 of neonatal life, plasma glucose and thyroid hormones increased only in the control group. Irrespective of maternal diet, insulin concentrations were similar on day 3 of life and declined ( Pb0.05) during the neonatal period in the S and PO piglets but were maintained in the E group.

K.S. Perkins, J.C. Litten, J. Emery and L. Clarke Department of Agricultural Sciences, Imperial College at Wye, University of London, Wye, Ashford, Kent, TN25 5AH, UK

Conclusion: It is concluded that the maternal diet during late gestation can have a pronounced influence on the growth and development of the newborn piglet, which can be further modified by

Conclusions: Different postnatal effects were seen in the circulations studied. SGA infants did not show a mesenteric response to feeding, even after recovery of baseline SMA velocity. They had a persistent reduction in coeliac axis velocity. References [1] Gladman G Arch Dis Child 1991;66:17—20. [2] Kempley ST Arch Dis Child 1991;65:115—8.

216 Table 1

Abstracts Neonatal endocrine profile on days 3 and 21 of neonatal life

Age (days)

Standard (n=14) 3

Glucose (mM) Insulin (ng/ml) T3 (ng/dl) T4 (Ag/dl)

4.72F0.4 0.13F0.02 107F7.6 4.62F0.3

Extra pellets (n=14)

Palm oil (n=14)

21

3

21

3

21

5.36F0.5 0.06F0.01 151F11.4 7.79F1.1

4.55F0.5 0.12F0.02 135F9.7 5.49F0.4

4.39F0.4 0.10F0.05 125F11.8 5.89F0.6

5.62F0.4 0.10F0.02 129F6.3 5.2F0.6

4.95F0.6 0.04F0.004 101F4.2 5.44F0.3

Values are meansFS.E.M.

the type of maternal dietary supplementation. It is likely that the differences in the physical development of the piglet are in part due to alterations in their endocrine profiles.

of life in premature infants with and without neonatal respiratory illness. R Thwaites 10.30—11.0 Coffee

Acknowledgements: The work was funded by DEFRA and Cotswold Pig Development Company. J.C.L. also wishes to thank Wye College for the provision of a PhD studentship.

Chairman Professor Terence Stephenson

Reference [1] Cieslak DG, Leibbrandt VD, Benevenga NJ. Journal of Animal Science 1983;57:955—9. Summer Meeting, Neonatal Society, Tours, France Friday 28th June 2002 0.8.00—08.55 Registration, coffee 08.55 Welcome Professor Elie Saliba and Dr Nikki Robertson Chairman Dr Nikki Robertson 09.00 The effect of early nasal CPAP on lung function and injury in a primate model of BPD. MA Thomson 09.15 Does infection with Ureaplasma urealyticum result in a specific clinical and radiological pattern in the preterm infant? U Theilan (introduced by Dr AJ Lyon) 09.30 Prediction of chronic lung disease from chest radiograph appearance at 7 days of age. A Greenough 09.45 Oxygen monitoring: too low or too high? National survey of oxygen saturation monitoring policies and the audit of the effect of change of policy in a single Neonatal Intensive Care Unit (NICU). C Lacamp (introduced by Dr W Tin) 10.00 First year morbidity among infants discharged home in oxygen. NJ Shaw 10.15 Relative risks of Respiratory syncytial virus (RSV) hospitalisation in the first 2 years

11.00 Young Investigator Prize Lecture Dr Helen Budge Academic Division of Child Health Nottingham, UK dProgramming of fetal adipose tissue development by maternal nutrition and prolactin.T 11.45 Changes in plasma cortisol with ventilation and analgesia in preterm infants. CM Wong (introduced by Dr I Laing) 12.00 Blood concentration of amethocaine and its metabolite after topical application. A Jain 12.15 Apnoea and periodic breathing. A Hassan 12.30—14.00 Lunch Chairman Dr Paul Johnson 14.00 The 6th annual Tizard Lecture Professor Petra Hu n ppi Director of Child Development Unit University Hospitals of Geneva Switzerland dSteroids and the developing brain—what have magnetic resonance techniques taught us?T 15.00 Secondary energy failure in a neonatal rat brain slice model. NJ Robertson 15.15 Brain natriuretic peptide concentrations predict haemodynamically significant patent ductus arteriosus in preterm infants. VF Puddy (Introduced by Dr S Calvert) 15.30—16.00 Tea

Neonatal Society Abstracts

217

Chairman Dr Andrew Lyon

Chairman Professor Elie Saliba

16.00 Increased sodium absorption across the nasal epithelium of ventilated moderately preterm infants on the first day of postnatal life. EA Gaillard 16.15 Effect of posture on oxygenation and respiratory function in prematurely born infants studied prior to discharge. RY Bhat 16.30 The effect of maternal dietary supplementation in late gestation on the behavioural development of the neonatal pig. JC Litten 16.45 Proportional assist ventilation—in vitro assessment of the effect of unloading on ventilator performance. JA Leipa ¨la ¨ 17.00 Reversibility of n-3 polyunsaturated fatty acids (n-3 PUFA) diet deficiency-induced alterations of dopaminergic neurotransmission: critical role of developmental stage. E Kodas 17.15 End of session 19.15 Coaches leave for Neonatal Society Dinner in Chinon

12.00 State of the art lecture

Saturday 29th June 2002 Chairman Professor Anne Greenough 09.30 Computerised breath sounds analysis in term and preterm infants. A Majumdar 09.45 Impaired splanchnic haemodynamic responses to enteral feeding in preterm growth restricted infants. EM Murdoch 10.00 Differential regulation of subcutaneous and visceral adipose tissue mass in early infancy. Modi N 10.15 The effects of maternal dietary fat supplement during late gestation on the growth performance and endocrine profile of the neonatal pig. KS Perkins 10.30 Effect of maternal nutrient restriction during late-gestation on hepatic prolactin receptor (PRLR) abundance in neonatal lambs. T Stephenson 10.45 Evaluation of Advanced Neonatal Nurse Practitioners: Confidential enquiry into the management of sentinel cases. MP Ward Platt 11.00 Scoring for the future: SNAPE-II works in Wessex. K Turnock (introduced by Dr R Thwaites) 11.15 Nursing workload by dependency category of baby in a tertiary neonatal intensive care setting. DWA Milligan 11.30—12.00 Coffee

Professor Pierre Gressens Laboratoire de Neurologie du De ´veloppement INSERM E9935 Ho ˆpital Robert Debre Paris, France dNeuroprotection in the newborn brain— interactions between stress, glutamate and glucocorticoidsT 13.00—14.00 Lunch 14.00 End of Scientific session 14.30—18.00 Optional tour of surrounding Chateaux Brain natriuretic peptide concentrations predict haemodynamically significant patent ductus arteriosus in preterm infants Victoria F Puddy1, Charles Amirmansour2, Anthony F Williams1, Donald RJ Singer3 (Introduced by Dr S Calvert) Regional Neonatal Unit1 and Department of Pharmacology and Clinical Pharmacology3 St George’s Hospital Medical School, London, Heart Science Centre, Imperial College at the NHLI, Harefield2 Background: Patent ductus arteriosus (PDA) is an important cause of morbidity in extremely preterm infants. Increased plasma BNP is a common feature of adult cardiac disease (1) and reflects the haemodynamic shunt in the PDA.(2) We measured plasma BNP concentrations in preterm infants to assess their value as a predictor of later haemodynamically significant PDA. Design: We studied 18 preterm infants (12 male), mean gestational age 30 weeks (range 24—34 weeks), mean weight 1.37 kg (range 0.54—2.13 kg) and 11 term healthy controls. Plasma BNP levels were measured by double-antibody radio-immunoassay on days 3, 5 and 7 of life and an echocardiogram performed on day 7. Results are for meanFS.E.M. Data were compared by Mann—Whitney U-tests. Results: On day 7, 12 infants had a normal echocardiogram (gestation 31F1 weeks; birth

218

Abstracts

weight 1.56F0.10 kg) and six an echocardiographically proven PDA without other cardiac disease (gestation 27F1 weeks; birth weight 0.99F0.15 kg). Four of these were treated successfully, one by surgical ligation, three with non-steroidal anti-inflammatory treatment; two had haemodynamically insignificant closing ducts. BNP concentrations on days 3, 5 and 7 ( Pb0.001) and LA: Aortic root ratio on day 7 ( P=0.04) were higher in infants with persisting PDA (Table). In the absence of PDA, plasma BNP levels by day 3 were similar to values in the healthy term neonatal range (9—190 pg/ml). Treatment of PDA reduced plasma BNP concentrations to similar levels (13F5 pg/ml; n=4). Conclusions: Plasma BNP levels are raised in preterm infants and fall to values in the adult range in the first week of life. In the first days of life plasma BNP levels are over 10-fold increased and remain markedly elevated in preterm infants with a persistent PDA at the end of the first week. Early measurement of plasma BNP is a potential method of predicting preterm infants at risk of a significant PDA who may require intervention. References [1] Cowie MR. Lancet 1997;350:349—5. [2] H Holmstro ¨m. Acta Paediatrica 2001;90:184—91. Day 7 Echo BNP (pg/ml) Day 3 no PDA (n=12) PDA (n=6)

159F64

Day 5 11F6

Day 7

LA/aortic root ratio Day 7

5F5

1.1F0.1 (n=10) 1907F345* 1734F592* 1334F397* 1.6F0.2 (n=6)y

* Pb0.001 vs. no PDA. y P=0.04 vs. no PDA.

Secondary energy failure in a neonatal rat brain slice model Robertson NJ, Bhakoo KK, Edwards AD and Cox IJ Department of Paediatrics, Imperial College of Science, Technology and Medicine, Hammersmith Campus, DuCane Road, London, UK

from 6—8 h following birth. The extent of these changes is closely related to the severity of brain injury and subsequent neurodevelopmental outcome [1]. The brain slice model is an integral part of neuroscience research as the cytoarchitecture and neuronal/glial interaction are preserved but there are important metabolic differences to the in vivo brain. We hypothesised that the neonatal rat brain slice model itself demonstrates secondary energy failure (SEF), which is delayed with hypothermia [2]. Methods: 350 Am brain slices were prepared from 7- and 14-day Wistar rat pups. Slices were continuously perfused in oxygenated Krebs—Henseleit buffer (KHB) in a Jeol Eclipse+11.7T MR spectrometer and interleaved 1H and 31P MR spectra were obtained over 8 h at 37 8C (n=7) and at 32 8C (n=8). The mean pHi and % change in mean PCr/Pi, lactate/NAA were calculated. Results: The 7- and 14-day models demonstrated pHi heterogeneity and similar values of PCr/Pi and lactate/N-acetylaspartate (NAA) 1 h after slicing. The metabolite ratio at 1 h (time when stabilization occurred) was defined as 100% and subsequent ratios were then compared. PCr/Pi declined over 8 h in both models and the rate of decline was similar in both the 7- and 14-day models. The PCr/Pi decline was delayed at 32 8C. Lactate/NAA increased at 4 h and plateaued; this increase in lactate/NAA was prevented at 32 8C. Data from the 14-day model are shown. Mean (S.D.) 1 h after 4h 4h 8h 8h parameter slicing (37 8C) (32 8C) (37 8C) (32 8C) in 14-day (stabilization) model PCr/Pi

100

lactate/ NAA pHi 1

100

pHi 2

7.50+0.01 7.21+0.03

65 (11)* 187 (3)# 7.49 (0.01) 7.21 (0.01)

110 (14)* 104 (6.3)# 7.66 (0.06) 7.33 (0.07)

58 (14) 178 (10) b 7.48 (0.06) 7.23 (0.01)

73 (10) 92 (3.5)b 7.65 (0.04) 7.32 (0.03)

*, #, b, pb0.05.

Background: Following perinatal hypoxia—ischaemia (HI) brain energetics apparently recover with resuscitation. Using magnetic resonance (MR) spectroscopy there is, however, a secondary decline in phosphocreatine (PCr)/inorganic phosphate (Pi), rise in cerebral lactate/creatine (Cr) and brain alkaline intracellular pH (pHi)

Conclusions: The brain slice model demonstrated SEF over 8 h in both the 7- and 14-day preparation and the energetic basis of neuroprotection with hypothermia was confirmed. Such a model may be of use in assessing the efficacy of other neuroprotective agents.

Neonatal Society Abstracts References [1] Azzopardi, et al. Pediatr Res 1989;25:445—51. [2] Thoresen, et al. Pediatr Res 1995;37:667—70. First year morbidity among infants discharged home in oxygen MW Beresford*, G Harrison**, NJ Shaw* *Liverpool Women’s Hospital, **Alder Hey Children’s Hospital, Liverpool, UK Background: Chronic lung disease of prematurity (CLD) is associated with significant long-term respiratory morbidity1. Infants particularly vulnerable are those discharged home in oxygen. Aims: To assess respiratory morbidity during 1-year follow-up of CLD infants discharged home on oxygen therapy. Methods: Pre-discharge oxygen requirements were set on clinical grounds. Before discharge, oxygen

Conclusions: Before discharge home, oxygen saturation profiles should performed on all infants to ensure optimum oxygen delivery. Reference [1] Bhutani VK. Clin Perinatol 1992;19:649—71. Effect of maternal nutrient restriction during late-gestation on hepatic prolactin receptor (PRLR) abundance in neonatal lambs M. Hyatt, J. Bispham, J. Dandrea, D. Walker, M.E. Symonds and T. Stephenson Academic Division of Child Health, School of Human Development, University Hospital, Nottingham NG9 2UH, UK

219 saturations were recorded (blind to clinicians) for 4 h. A home-oxygen nurse specialist prospectively collated infant’s oxygen requirements, hospital admissions and attendances, and details of acute life threatening events (ALTEs), over the first 12 months following discharge. Results: Sixteen infants were studied. Median (range): gestational age was 28 weeks (24—32); birth-weight was 938 g (448—1638); discharge oxygen requirement was 0.20 l/min (0.05—0.50) via nasal cannulae; duration of oxygen requirement (up to 12 months corrected age) was 310 days (83—462). One infant died, seven required admission for respiratory causes on 3 occasions (2—5) for a total of 13 days (7—117). Eight infants had ALTEs on 2 occasions (1—5). Their discharge oxygen saturation profiles were significantly lower when compared to those not having ALTEs ( pb0.05), despite being on oxygen therapy. The graph shows the median and lower 5th centile for cumulative percentage oxygen saturation for the two groups.

Introduction: Maternal nutrition during late-gestation may influence neonatal growth by altering maturation of the hypothalamo—pituitary—adrenal axis (1). Circulating PRL levels and PRLR abundance normally peak near to term (2). However, the extent to which the long and short forms of PRL receptor are nutritionally regulated in hepatic tissue remains to be determined. Methods: Fourteen primiparous twin pregnant Border Leicester cross Swaledale ewes were entered into the study. Six ewes were allocated to the control (C) group and consumed 100% of total metabolisable energy (ME) requirements (for both ewe maintenance and growth of the conceptus in order to produce a 4.5 kg lamb at term). The remaining eight ewes were nutrient restricted (NR)

220

Abstracts

and consumed 60% of total ME requirements. All ewes lambed normally at term, and one twin was euthanased with an overdose of barbiturate (100 mg kg
1 pentobarbital sodium: Euthatal) within 6 h of birth to enable liver sampling with the remaining twin being reared with its ewe until 30 days after birth. Total RNA was extracted from the liver, reverse transcribed and abundance of PRLR measured by polymerase chain reaction of reverse transcribed product using oligonucleotide primers specific to the long and short forms of PRLR (3). Results are given as means with their standard errors in arbitrary units (a.u) as a ratio of 18S rRNA and are expressed as a percentage of a reference sample present on all gels. Differences in nutritional treatments were analysed using a Mann—Whitney U-test. Results: Sampling age

4h 30 days

C NR C NR

Conclusion: Maternal nutrient restriction over the final month of gestation resulted in lower hepatic mRNA abundance for both long and short forms of PRLR at birth and 30 days of postnatal age. This difference was only significant at birth for the short form of PRLR. Downregulation of PRLR mRNA occurred in the absence of any significant difference in lamb or liver weights, but may contribute to significant alterations in later growth and metabolic function. References [1] Edwards LJ, Symonds ME, Warnes KE, Owens JA, Butler TG, Jurisevic A, McMillan IC. Endocrinology 2001;142:1778—85. [2] Phillips ID, Anthony RV, Butler TG, Ross JT, McMillen IC. Endocrinology 1997;138:1351—4.

Lamb weight (kg)

Liver weight (g)

PRL Receptor Long form mRNA (a.u)

PRL Receptor Short form mRNA (a.u)

Mean

S.E.M.

Mean

S.E.M.

Mean

S.E.M.

Mean

S.E.M.

4.1 3.6 16.4 14.3

0.3 0.2 1.2 1.4

85.5 74.0 251.1 258.7

8.0 3.0 44.5 49.0

404.9 204.6 173.3 39.6

132.5 131.5 57.2 5.9*

472.0 57.9 195.6 47.3

212.8 21.8* 60.9 12.7*

Significantly different from control at *Pb0.05 level, as measured by Mann—Whitney U-test.

[3] Nixon AJ, Ford CA, Wildermoth JE, Craven AJ, Ashby MG, Pearson AJ. J. Endocrinol. 2002; 172:605—14. Does infection with Ureaplasma urealyticum result in a specific clinical and radiological pattern in the preterm infant? Theilen U1, Lyon AJ1, Fitzgerald T2, Hendry M3, Keeling J4 Neonatal Unit1 and Department of Radiology2, Simpson Memorial Maternity Pavilion, Edinburgh, UK. Departments of Radiology3 and Pathology4, RHSC Edinburgh, UK Background: Infection with Ureaplasma urealyticum (Uu) has been associated with chronic lung disease in preterm infants. Aim: To determine if infection with Uu from birth causes a specific acute respiratory disease which may be the precursor of long-term lung damage. Methods: 60 ventilated babies b30 weeks had tracheal secretions cultured for Uu. Clinical details in the first 10 days were reviewed retrospectively. Chest X-rays around days 1, 5 and 10 were

independently reported, for agreed features, by 2 radiologists, blinded to the baby’s Uu status. Each feature was scored 0—4 dependent on the lung quadrants involved. Comparisons were by Chi square and Mann—Whitney U-test. Results: 25 were Uu positive and in these chorioamnionitis was more common (13/24 vs. 5/30, p=0.005) and maximum white count higher (median (range) 28 (8—92) vs. 19 (7—70), p=0.015). Despite being less mature (25 (24—29) vs. 26 (24—29) weeks, p=0.016) the Uu+ve group were weaned earlier to the same mean airway pressure and FiO2 as the Uu
ve group (day of lowest MAP 4 (2—10) vs. 6 (1—10), p=0.039); day of lowest FiO2 2 (1—6) vs. 3 (1—10), p=0.052). The Uu+ve group then deteriorated, needing increased ventilatory support (day 10: MAP 7 (5—14) vs. 5 (0—12), p=0.002; FiO2 39 (25—66) vs. 25 (21—72), p=0.001). Changes of RDS were less widespread on day 1 X-rays in the Uu+ve group (median score 1 (0—2) vs. 3 (0—4), p=0.038). By day 5 the Uu+ve group had more emphysema and this increased further by day 10 (score 1 (0—3) vs. 0 (0—1) p=0.009). Conclusion: Ventilated preterm infants infected with Uu have a specific clinical and radiological

Neonatal Society Abstracts course in the first 10 days. Their initial respiratory disease is less severe but they then deteriorate with increasing ventilatory requirements and more emphysematous change on X-ray. They have significantly higher white cell counts suggesting ongoing inflammation. Reference [1] Lyon A. Eur J Pediatr 2000;159:798—802. The effect of early nasal CPAP on lung function and injury in a primate model of BPD MA Thomson1, BA Yoder2,3,4, D Catland2,4, H Martin3, V Winter2, JJ Coalson2 Imperial College of Science, Technology, and Medicine, London, UK; University of Texas Health Science Center, San Antonio; Southwest Foundation for Biomedical Research, San Antonio; Pediatrix Medical Group, San Antonio, TX, USA Background: No single treatment is likely to prevent Bronchopulmonary dysplasia (BPD). Minimizing volutrauma may reduce secondary lung injury and improve subsequent lung development. The study aim was to investigate the effect early nCPAP following prophylactic surfactant had on lung function and injury in the 125-day premature baboon model of BPD.0. Methods: Following intramuscular betamethasone at 48 and 24 h prior to birth, 125-day baboons (term, 185 days) were delivered by caesarean section. Surfactant (Curosurfk 200 mg/kg) was given before the first mechanical breath, and repeated (100 mg/ kg) at 6 h. Caffeine citrate (20 mg/kg) was given at 1 and 12 h age followed by a daily maintenance dose (10 mg/kg). Low tidal volume (4—6 ml/kg) positive pressure ventilation (PPV) was aggressively weaned over the first 24 h. Extubation to nCPAP (Infant Flow Driverk) was attempted at 24 h age. Serial physiological parameters were recorded. Pulmonary function tests were obtained for the first 24 h. Lung histology was examined following elective necropsy at 28 days. Data was compared to previously described controls1. Results: All six nCPAP animals were successfully extubated at a median 26.5 h of life (range 24—29). Three required short periods of reventilation, median length of ventilation 47 h (range 36—53). Five survived to 28 days, one died at 19 days from NEC and systemic sepsis. Significant improvements in oxygenation index, a/ A ratio, FiO2, mean airway pressure, PaO2, PaCO2,

221 and mean arterial blood pressure were seen at multiple time points throughout the study in nCPAP animals compared to prior controls. Expiratory airway resistance and thoracic compliance were improved at 6, 12, and 24 h of age ( pb0.05). At necropsy, lungs of nCPAP animals were evenly expanded without gross evidence of atelectasis and infection, findings frequently present in PPV animals. Histopathologically, the evenly expanded nCPAP lungs showed remarkably thin saccular walls with minimal if any fibroproliferation. PPV lungs showed more unevenly expanded saccules with varying degrees of fibroproliferation. In spite of the more normal appearance of the lungs in the nCPAP animals, secondary crests and alveoli were rare, a finding previously documented in the PPV animals. Morphometric studies revealed no significant differences in mean linear intercept and volume to area ratio determinations, but internal surface area measurements were significantly higher in the nCPAP group when compared to the PPV animals ( pb0.04). Conclusion: Early use of nasal CPAP, coupled with prophylactic surfactant can be used to successfully manage immature primates with RDS during the late canalicular stage of lung development. This approach results in dramatically improved lung histology at 28 days age, but still does not allow for normal alveolization. Reference [1] Coalson JJ, Winter VT, Siler-Khodr T, Yoder BA. Neonatal chronic lung disease in extremely immature baboons. AM J Respir Crit Care Med 1999;160:1333—46. Odds ratios for Respiratory syncytial virus (RSV) rehospitalisation in the first 2 years of life in premature infants with and without neonatal respiratory illness Richard Thwaites1, James Piercy2, James Ryan2, Phil James3 1. Child Health, St. Mary’s Hospital, PORTSMOUTH, PO3 6AD, UK. 2. Mapi Values, MACCLESFIELD, SK10 5 JB, UK. 3. CHKS, Arden Rd, ALCESTER, B49 6HN, UK Hypothesis: Premature birth and neonatal respiratory illness are both associated with higher

222

Abstracts

rate and duration of RSV rehospitalisation in infancy. Introduction: RSV infection causes significant problems for ex-premature infants particularly those with Bronchopulmonary Dysplasia1. We used the CHKS database, which covers 55% of the UK, to quantify the odds ratios (OR) and lengths of stay (LOS) for RSV hospitalisations in term and preterm infants with and without neonatal respiratory problems. Analysis was restricted to hospitals with complete data for the whole time period (equivalent to about 30% of UK births). Methods: Admissions of children less than 2 years old between Jan 1998 and Dec 2001 were analysed. Data was extracted on episodes with RSV specific ICD-10 codes as discharge diagnosis (n=14,728). Where possible such admissions were linked back to a birth admission record (n=8,597). All births where the baby was discharged alive (n=694,503) for the same 4-year period were

assessed for drisk factorsT using ICD-10 codes for gestation and neonatal respiratory illnesses.

ICD-10 Codes reviewed and descriptors RSV Specific

J12.1 J20.5 J21.0

Prematurity

P07.2 P07.3

RSV pneumonia Acute bronchitis due to RSV Acute bronchiolitis due to RSV Gestational ageb28 weeks Gestational age 2836+6 weeks

Neonatal respiratory illness P20 P21 P22 P23 P24 P25 P26 P27 P28

Intrauterine hypoxia Birth Asphyxia RDS, TTN Cong. pneumonia Aspiration syndrome Air leak syndrome Pulm. haemorrhage Chronic lung disease Misc. (incl. apnoea)

Results: Group (n)

Gestation code

Resp code (P20-8)

RSV adm. n (% of Gp)

OR RSV adm. [95% C.I.]

Mean LOS (d) [95% C.I.]

1 2 3 4 5 6

P07.2 P07.2 P07.3 P07.3 None None

P27 present Not P27 Any None Any None

10 (11.0) 32 (2.8) 185 (3.4) 314 (2.7) 1315 (2.1) 6741 (1.1)

11.99 2.64 3.21 2.52 1.97 1.00

5.7 6.8 4.6 4.8 4.5 3.5

(91) (1144) (5465) (11687) (62039) (614077)

[7.07—20.31] [2.01—3.46] [2.86—3.60] [2.30—2.75] [1.88—2.06] [N/A]

[3.09—8.31] [4.70—8.92] [3.91—5.25] [4.35—5.32] [4.06—4.94] [3.36—3.55]

OR RSV admission: Gps 1 vs. 2: p=0.001, 3 vs. 4: p=0.001; 1, 2, 3, 4 and 5 vs. 6 all pb0.001. LOS: Gps 1 vs. 2: p=0.576, 3 vs. 4: p=0.536, 1 vs. 6: p=0.08. 2, 3, 4 and 5 vs. 6: all pb0.001.

Discussion: Absolute rates of RSV admission shown are significant underestimates as only 58% could be linked back to a birth record, furthermore we only include those babies with confirmed RSV, coded as such by CHKS. Adjusting for unlinked records (assuming these occurred at the same rate in each group) confirmed RSV admission rates for groups 1—6 would rise to 18.9%, 4.8%, 5.8%, 4.6%, 3.6% and 1.9%, respectively. The term group 5 with neonatal respiratory illness and later RSV merits further investigation and may provide new insights into RSV pathogenesis. This study was supported by an educational grant from Abbott Laboratories, Maidenhead, UK.

Reference [1] Groothuis JR, Gutierrez KM, Lauer BA. Pediatrics 1988;82:199—203. Scoring for the future: SNAPPE-II works in Wessex Karen Turnock and Simon Struthers Neonatal Unit; Princess Anne Hospital; Coxford Road; Southampton SO16 5YA, UK (introduced by Richard Thwaites) Introduction: Routine data collection is most useful if comparisons can be made between units and areas for improvement or research identified. Scoring systems are intermittently maligned but are increasingly providing audit and benchmarking

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data in critical care. The SNAPPE-II score was developed from the complex SNAP score in Canada, and is applicable to all infants admitted for ongoing neonatal care within 48 h of birth1. The score is now used extensively in North America. This data collection exercise was undertaken to assess the usefulness of SNAPPE-II in the UK population in comparison with the Canadian data and the UK developed CRIB score.

appears to have good discrimination and full calibration would be possible. It is quick and easy to use and may provide a useful tool as the move for more centralisation and benchmarking of neonatal care gathers pace.

Methods: Physiological and demographic data were taken from routine charts and used to calculate the SNAPPE-II score, and, where relevant (in infants less than 31 weeks gestation or less than 1500 g) the CRIB score. Senior house officers and specialist registrars in the Southampton (S) and Portsmouth (P) neonatal units undertook the scoring over a period of 14 months. The discrimination of the scores was analysed with receiver operating characteristic (ROC) curves and compared with the Canadian data. Comparisons of mortality were made using standardised mortality ratios (SMR) and relative risks calculated for each score rank.

Evaluation of advanced neonatal nurse practitioners: confidential enquiry into the management of sentinel cases

Results: A total of 700 infants were scored. This represented 81% of the infants eligible for scoring. At unit S 390 infants were scored of 409 eligible and 630 total admissions. All those missed in unit S were short stay term infants. At unit P the corresponding figures were 310 of 460 eligible and 595 total. Infants of all types were missed in unit P without apparent bias. Non-eligible babies (26%) were over 2 days old on admission, discharged to the postnatal wards by the day following admission, or admitted for terminal care only. A few infants were transferred to other units within 12 h of birth. The area under the ROC curve for the total population scored with SNAPPE-II was 0.91 (0.85—0.97). For the CRIB population—23% of scored admissions—the area under the ROC for SNAPPE-II was 0.87 (0.77—0.98); with the area under the ROC curve for the corresponding CRIB scores of 0.87 (0.76—0.96). Compared to Canadian data, the distribution of scores was similar in the two populations. The overall SMR was 1.15, 0.97 for infants b1500 g and 1.6 for infants N1500 g. The relative risk compared to the Canadian predictions showed no significant differences in mortality, confidence limits were wide due to small numbers.

Methods: A novel methodology for confidential enquiry was developed, which allowed aspects of high quality practice to be captured as well as suboptimal care. Sentinel cases included all babies who within the first postnatal week either died, or were transferred out, or who developed convulsions. Five other hospitals, all with different models of neonatal care, but all based on hierachies of medical staff, were chosen as comparators. Eight dimensions of care were each rated on a scale of 0 to 4 (from seriously deficient to exemplary). Case notes for babies born between April 1998 and March 1999 were anonymised and assessed blind by four raters. If predefined standards of concordance were not met, the notes were rated by a panel independent of any of the participating hospitals, and this rating was taken as definitive. Arithmetical means of the scores were taken for each relevant dimension of care for each case, and the mean for each case was averaged for each hospital.

Conclusion: Although scoring is not the most scintillating of topics, this simple model provides an encouraging means of comparing populations across the entire spectrum of neonatal care. It

Reference [1] Richardson, et al. J Ped 2001;138(1):92—100.

Ward Platt MP and Brown K on behalf of the Ashington Advanced Neonatal Nurse Practitioner Evaluation Group Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK Purpose of the study: To evaluate the quality of care delivered by Advanced Neonatal Nurse Practitioners at Ashington Hospital.

Results: 82 cases were analysed. The dimension relating to terminal care had insufficient numbers for inclusion. The lowest score for any single case was 0.49 and the highest 3.07; neither case was from Ashington. Mean scores for the comparator hospitals were 1.80, 2.13, 2.32, 2.23, 2.43. The mean for Ashington was 2.35. Results for each dimension for Ashington are related to themeans for all the comparator hospitals in the table below. Ashington scored above average on six out of the seven dimensions.

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Abstracts

Resuscitation Admission Stabilisation Investigations Communication Treatment Transfer out

Comparator average

Ashington

2.33 2.27 2.14 2.39 1.84 2.16 2.07

2.59 2.37 2.45 2.25 2.07 2.5 2.21

Conclusions: The quality of care of these sentinel cases appeared to be at least as good when provided by Advanced Neonatal Nurse Practitioners alone as when delivered by medical models of neonatal care. These data support the contention that good quality neonatal care can be delivered by Advanced Neonatal Nurse Practitioners alone, and does not require the presence of resident junior paediatricians. Changes in plasma cortisol with ventilation and analgesia in preterm infants C Mae Wong, Elaine M Boyle, Ian A Laing, Joan Yorke, Jaqi Armstrong, John Smith, Paula C Midgley, Neil McIntosh Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK Table 1 Postnatal day 1 2 3 7 14

Ventilated

Not ventilated

N

Cortisol

N

Cortisol

34 35 36 26 19

309.7 310.0 209.1 273.1 211.6

18 17 39 45 38

99.5 107.8 133.3 176.9 147.7

P value 0.006 0.001 0.002 0.009 0.05

Table 2 Postnatal day 1 2 3 7 14

Morphine

No morphine

N

Cortisol

N

Cortisol

19 17 17 6 4

351.1 292.4 207.3 350.1 207.6

15 18 19 20 15

199.1 356.1 286.8 273.1 211.7

P value 0.19 0.30 0.68 0.93 1.00

Background: Plasma cortisol can be used as a marker of pain and stress in neonates1. Preterm infants often require assisted ventilation but analgesia is not used routinely. Aims: To investigate the effect of ventilation on plasma cortisol levels in preterm infants, and to see if analgesia affects these levels. Methods: From July 2000 to December 2001, longitudinal once-daily morning blood samples were collected from 88 neonates V32 weeks gestation. Plasma cortisol was measured by a direct in-house radioimmunoassay. Infants with painful conditions were excluded. No infant received postnatal steroids. Results were analysed by Mann—Whitney U-test. Results: Median cortisol values (nmol/L) are tabulated. Table 1 shows results from the 88 neonates grouped by ventilation. All the ventilated babies are shown in Table 2 grouped by analgesia. Within this ventilated cohort was a subgroup of infants randomised in the NEOPAIN Trial to morphine or placebo infusions. Samples taken during assisted ventilation showed significantly higher cortisol levels. However, there was no significant difference in cortisol levels between the groups receiving analgesia or no analgesia. Similar results were obtained with samples from the subgroup of NEOPAIN infants. There was no difference in gestation or birth weight between those who received analgesia and those who did not. Conclusions: Assisted ventilation is associated with raised plasma cortisol levels in preterm infants. This could be due to the underlying cause of the need for ventilation, or the pain or stress of ventilation itself. However, analgesia has no effect on these levels in ventilated infants, suggesting either that morphine is ineffective in ameliorating pain, or that the stress of ventilation is not related to pain. Reference [1] Anand KJ. NEJM 1992;326(1):1—9.