The Neonatal Society

Abstracts Summer Meeting 2001, Nottingham

Link to meeting programme - click here

Pericardial effusions and cardiac tamponade associated with neonatal long lines - are they really a problem?

Beardsall K, White DK, Kelsall AWR.
Neonatal Intensive Care Unit, Rosie Hospital, Addenbrooke's Hospital, Cambridge. CB2 2QQ

Introduction: Percutaneous long lines (PLL) are now routinely used in neonatal intensive care units (NICU) and provide a safe and secure route of vascular access for the administration of parental nutrition. A number of different complications have been reported with pericardial effusion/cardiac tamponade being the most serious and potentially fatal. Parents have recently been made aware of this complication following media coverage. The neonatal literature contains only a few case reports. There are no studies that investigate the incidence of pericardial effusion/cardiac tamponade associated with the use of PLLs.
Methods: We have conducted a retrospective survey to determine the incidence of this problem over the last 5 years. A questionnaire was sent to the lead neonatal/paediatric clinician in all United Kingdom hospitals providing neonatal/special care.
Results: 243 questionnaires were sent and 173 returned (71%). 149 (86%) of the responding units routinely inserted PLLs. Of these, 103 (69%) inserted <50 PLLs and only 21 (14%) inserted > 100 PLLs per year. From the replies, we estimate that approximately 8,000 PLLs are inserted per annum. All units check the position of PLLs by x-ray but only 41 (27%) routinely use intravenous contrast. Eighty-six (58%) aimed to position the PLL in the vena cavae with the line tip outside the heart. Sixty-three (42%) were content with the PLL tip in the right atrium. Over the 5-year study period, 63 cases of pericardial effusion/cardiac tamponade were identified. Information was available in 62 cases. Thirty-four (55%) infants survived. The condition was suspected in 42 cases (68%) and confirmed by echocardiography in 28 (45%). Pericardial taps were attempted in 32 (52%). Of the 28 infants who died, diagnosis was made at post mortem in 20. Over the study period we estimate that 1.6 pericardial effusions/cardiac tamponades will occur for every 1,000 lines inserted, with a fatality rate of 0.7 per 1,000 PLLs inserted.
Conclusions: There is wide variation in the use of PLLs in neonates in the UK. The incidence of pericardial effusion/cardiac tamponade is very low. A significant proportion are diagnosed after death. Our figures almost certainly underestimate the incidence as it is a retrospective study. In addition, further cases may have been missed if post mortems were not performed. We aim to conduct a prospective study to determine the extent of the problem.

References
1. Beattie PG, Kuschel CA and Harding JE. Pericardial effusion complicating a percutaneous central venous line in a neonate. Acta Paediatr 1993;82:105-7.
2. Harms K, Herting E, Kruger T, Compagnone D and Speer CP. Percutaneous silastic catheters in newborn and premature infants. A report of experiences with 497 catheters in 5 years. Monatsschr Kinderheilkd 1992; 140(8):464-71.
3.Khilnani P, Toce S and Reddy R. Mechanical complications from very small percutaneous central venous silastic catheters. Critical Care Medicine 1990;18(12):1477-1478.

Disease severity markers predicting adverse outcome in term infants with respiratory failure.

Charlotte C Bennett¹, Ann Johnson², David J Field³.
On behalf of the UK Collaborative ECMO Trial Group.
¹ John Radcliffe Hospital, Oxford. UK. ² NPEU, University of Oxford, UK.
³ Leicester University, Leicester. UK

Abstract
Objective To determine clinical variables predicting outcome in a group of 185 infants born at 35 weeks gestational age or above who developed severe respiratory failure defined by oxygenation index equal to or greater than 40.
Methods A variety of disease severity markers were selected and the association between the chosen variable and outcome was determined. Adverse outcome was defined by death or disability at four years of age in survivors. Receiver operator characteristic (ROC) plots were constructed for variables with continuous data and relative risk (RR) with 95% confidence intervals (CI) calculated for binominal data.
Results : Clinical variables predicting mortality and disability at 4 years.
Clinical variable                                       RR (95% CI) p value
Congenital diaphragmatic hernia                 1.38 (1.22-1.56) p<0.001
Birthweight less than 3kg                          1.34 (1.16-1.54) p<0.001
Continued conventional care i.e.: not ECMO 1.84 (1.14-2.97) p=0.003

Clinical variables predicting disability at 4 years in survivors.
Clinical variable RR (95% CI) p value
Seizures requiring treatment                     2.02 (1.63-2.51) p=0.002
Sepsis - documented or suspected            1.58 (1.09-2.30) p=0.01
Full sucking feeding at over 14 days of age 6.47 (2.24-19.2) p<0.001
Days in hospital over 30 days                   1.79 (1.22-2.61) p=0.02
Supplementary oxygen at discharge           1.91 (1.57-2.34) p=0.02

Conclusions This study has identified clinical variables that predict adverse outcome for term infants with severe respiratory failure. The results could assist clinicians caring for these babies and when counselling their families.
Key words Neonatal respiratory failure, outcome.

Correspondence to ccbennett@doctors.org.uk

The role of pulmonary surfactant proteins A, B and D in preterm infants ventilated for respiratory distress receiving different surfactant therapies

MW Beresford, NJ Shaw,
Neonatal Unit, Liverpool Women's Hospital, Liverpool L8 7SS, UK

Background
Surfactant proteins (SP) have fundamental actions in surfactant metabolism, function and immunoregulation1-3. There is no published data regarding SP concentrations using non-bronchoscopic bronchoalveolar lavage (NB-BAL) from infants with respiratory distress syndrome (RDS) and those who subsequently develop chronic lung disease (CLD). No study has explored postnatal changes in SP-B and SP-D or evaluated the effects of different surfactant preparations on lavage SP concentration.

Aims
To investigate bronchoalveolar SP concentrations in BAL fluid from preterm infants ventilated for RDS and randomised to receive either a natural or a synthetic surfactant.

Methods
Standard NB-BAL was performed on infants <30 weeks gestation randomised to receive poractant alfa or pumactant. Samples were collected on a daily basis (first week) and twice weekly thereafter. SP-A, SP-B and SP-D quantification took place using ELISA techniques and comparisons made between outcomes including CLD and death as well as surfactant type. SP levels expressed as concentration per volume of lavage fluid (ng/mL BAL). All results presented here as median (interquartile range).

Results
Median of 262 samples were analysed from 50 infants. Gestational: 27 weeks (26-28); birth weight 882 grams (712-1016); 34 male; 25 received natural (poractant alfa), 25 artificial (pumactant) surfactant.
BAL concentration of all SP rose significantly over the first postnatal week (p=0.04, 0.02 and 0.001 respectively). SP-B levels, but not SP-A or SP-D, were significantly higher over the first 3 days in poractant alfa treated infants (p<0.02). Infants developing CLD by day 28 had significantly lower SP-D levels on day 2 (p=0.035) and day 3 (p=0.041) than those without. SP-A and SP-B concentrations did not differ significantly between these groups over the first 4 days. On day 2, SP-B levels (5 {3-340} vs 350 {107-1,250}, p=0.033*) and SP-D levels (359 {217-526} vs 698 {400-1091}, p=0.04**), but not SP-A levels, were significantly lower in infants dying compared to those surviving

Surfactant protein concentration and mortality:
            Dying                       Surviving


Conclusion
BAL SP-B and SP-D concentration appear to influence significantly clinical outcome from RDS unlike SP-A, despite its important in-vitro contributions to surfactant metabolism and function.

1. Creuwels LAJM, van Golde LMG, Haagsman HP. Lung 1997;175:1-39
2. Floros J, Kala, P. Annu Rev Physiol. 1998;60:365-384
3. Eggleton P, Reid KBM. Current Opinion Immuology 1999;11:28-33

Erythrocyte Essential Fatty Acid Concentrations in preterm and full-term neonates

Besheya TA¹, Clarke P², Reed P¹, Kane J¹, Weinkove C¹.
¹ University of Manchester, Department of Medicine (Clinical Biochemistry), Clinical Sciences Building, Hope Hospital, Salford, M6 8HD. UK
² Neonatal Intensive Care Unit, Hope Hospital, Salford, M6 8HD. UK

BACKGROUND: Increased susceptibility to infection and growth failure are common complications of prematurity, yet also features of Essential Fatty Acid (EFA) deficiency [1]. Preterm infants may be born with poorer EFA status compared with term infants [2] and this could render them more prone to these complications.

AIMS: To determine whether preterm infants are deficient in EFAs at birth by comparing the fatty acid content of erythrocytes in full-term and preterm infants; to assess if measurement of the EFA content of erythrocytes might be used as an indicator of the nutritional status of preterm neonates.

METHODS: Venous blood samples were collected on the first postnatal day from preterm infants admitted to the Neonatal Unit and cord blood samples were obtained at birth from full-term neonates. Erythrocyte EFA concentrations were measured by an isocratic HPLC method using fluorimetric detection, after separation on a C-8 Spherisorb column [3].

RESULTS: 19 preterm infants with median gestation 30 weeks [range 25 - 36] and 20 full-term infants with median gestation 39 weeks [range 37 - 41] were studied.

Erythrocyte fatty acid concentrations are expressed in mmol/1012 RBC

CONCLUSIONS: Excepting eicosatrienoic acid, all erythrocyte EFA concentrations were unexpectedly higher for preterm infants. The greater concentration of maternally-derived fatty acids in erythrocytes of premature infants may reflect a higher demand for EFAs in the preterm fetus. Our analysis of erythrocyte EFA content does not provide evidence for congenital EFA deficiency in preterm neonates. These observations preclude the use of erythrocyte EFA concentrations as an index of neonatal nutritional status.

[1] Paulsrud JR, Pensler L, Whitten CF, Stewart S, Holman RT. Am J Clin Nutr 1972;25:897-904
[2] Leaf AA, Leighfield MJ, Costeloe KL, Crawford MA. J Pediatr Gastroenterol Nutr 1992;14:300-8
[3] Besheya TA, Reed P, Kane J, Weinkove C. Proceedings of the ACB National Meeting (1998):p34

The effect of antenatal corticosteroids in triplet pregnancies on fetal growth , survival and neurodevelopmental outcome.

A D'Amore¹ JS Ahluwalia¹ I Cheema¹ S Kaptoge² AW Kelsall^1
1Neonatal Intensive Care Unit, Rosie Maternity Hospital Hills Rd Cambridge
²Centre for Applied Medical Statistics, University of Cambridge Institute of Public Health,Robinson Way Cambridge

Background The incidence of triplet pregnancies has increased as a result of infertility treatment. Advances in obstetric and neonatal intensive care including the use of antenatal
corticosteroids and postnatal surfactant have resulted in improved survival in premature infants1. Concerns have been raised that multiple courses of antenatal corticosteroids may have adverse effects on fetal growth and longer term neurodevelopment2. There are few data on their use in multiple pregnancy.

Aim To review the outcome of triplet pregnancies, and in particular determine the
impact of antenatal steroids on fetal growth, survival and developmental outcome.

Methods Retrospective case note review of infant and maternal records following admission to a single tertiary neonatal unit.

Results Sixty triplet pregnancies were identified over 14 years (1986-1999). 173 live births were included in the analysis and divided into groups according to maternal antenatal corticosteroid exposure.

156 infants (90%) of live triplet births survived to discharge. In 46 pregnancies (76%) all the triplets survived. Survival at greater than 28 weeks was 98.9 %. The overall perinatal mortality rate for this cohort was 92/1000 live births. Data on neurodevelopmental outcome at 1 year were available for 143 survivors (91%), only 5 infants had documented problems.
3 infants had spastic diplegia and 1 infant had hydrocephalus; these were in the non-steroid group.
Chi -square test and probability models showed that only gestation had a significant effect on survival. There was no significant effect of steroid exposure on head circumference at birth or on fetal growth restriction.

Conclusion Survival from triplet pregnancy is high. Antenatal steroids are not associated with adverse outcome.

References:
1. Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomised trials, 1972-1994. Am J Obstet Gynecol 1995;173:322-35.

2. French N, Hagan R, Evans S, Godfrey M, Newnham J. Repeated antenatal corticosteroids: size at
birth and subsequent development. Am J Obstet Gynaecol 1999;180:114-21

The Angiotensin Converting Enzyme (ACE) DD genotype is associated with worse perinatal cardio-respiratory adaptation after pre-term birth.

David Harding1, Hugh Montgomery², Sukhbir Dhamrait², Steve Humphries², Andrew Whitelaw¹ , Neil Marlow.⁴

¹Division of Child Health, University of Bristol, UK, ²Department of Cardiovascular Genetics, The Rayne Institute, University College London, UK, ³AcademicDivision of Child Health, Queen's Medical Centre, Nottingham, UK.
Contact Person: David Harding, (david.harding@bristol.ac.uk)

The ACE gene is polymorphic (DD/ID/II). The absence (deletion, D) rather than the insertion (insertion, I) of a 287 base pair fragment is associated with higher tissue and plasma ACE activity, less efficient metabolic and cardiac performance and lower VO2max. We hypothesised that DD genotype would be associated with worse perinatal cardio-respiratory stability. ACE genotype was determined from DNA extracted from the Guthrie cards of 194 preterm infants. All were born at 23 - 32 weeks gestation and had participated in a prospective outcome study. Perinatal variables were examined for association with ACE DD genotype. Primary analysis was performed on the whole group and secondary analysis by gestational age groups. In the whole study group there was a trend in the DD patients towards worse acute perinatal indices (foetal distress, worse base excess and minimum and maximum O2 requirement in the 1st 12 hours of life, p=0.09 - 0.049). DD infants > 29 weeks adapted significantly worse than ID/II patients (foetal distress, DD 18 [45%], ID/II 27 [25%] p=0.017: worse BE in 1st 12 hours, DD -4.8 (SEM + 0.2), ID/II -2.9 (SEM + 0.1), p=0.014: Min. fiO2 in 1st 12 hours, DD 0.34 (SEM + 0.03), ID/II 0.28 (SEM + 0.01), p=0.009: Max. fiO2 in 1st 12 hours DD 0.43 (SEM + 0.02), ID/II 0.035 (SEM + 0.01), p=0.015: blood pressure support in 1st 12 hours, DD 12 [30%], ID/II 15 [14%] p=0.032). The ACE I/D polymorphism may influence the condition of preterm infants in the perinatal period.

Changes in Cerebral Oxygen Extraction in Preterm Infants with Severe Cerebral Injury

Kissack CM, Garr R, Wardle SP, Weindling AM
Department of Child Health, University of Liverpool

Background: A good coherence between systemic mean arterial blood pressure and cerebral oxygenation (expressed as HbD, the difference between HbO and Hb as measured by near infrared spectroscopy) has been shown to have an association with increased incidence of severe cerebral injury, when considering grade 3 or 4 intraventricular haemorrhage (IVH) and periventricular leucomalacia (PVL) as a single entity1. Other work has not demonstrated any difference in the incidence of cerebral injury, again considering haemorrhagic parenchymal infarction (HPI), IVH, and PVL together, when comparing hypotensive with normotensive infants2.

Aim: We aimed to study the changes in cerebral fractional oxygen extraction (CFOE) over the first three days after delivery, and to separately compare the findings in those with HPI and PVL with those who had no cranial ultrasound abnormality.

Methods: CFOE was calculated from the cerebral venous saturation, measured using near infrared spectroscopy (Hammamatsu 500, Hammmatsu UK Ltd) with the partial jugular venous occlusion technique3. MABP was measured invasively via indwelling umbilical arterial catheter. LVO was measured using 2D and Doppler echocardiography. Cranial ultrasounds were performed as part of the routine care of the infants.

Results: 36 conventionally ventilated preterm infants were recruited, with median (range) gestation 26 weeks (23-30) and birthweight 929g (452-1378). Two infants had HPI and four had PVL on cranial ultrasound. These six infants did not differ in gestation or birthweight from the 30 with normal cranial ultrasound. The changes in CFOE over the three days are illustrated in figure 1.

Figure 1: CFOE for the first three days after birth for two infants who developed HPI (---), four infants who developed PVL (       ) and mean values for 30 infants with no cranial ultrasound abnormality (       ).

Conclusions: The infants who went on to develop HPI had several measurements of CFOE higher than the 95th centile for those infants with no cerebral injury. Infants who developed PVL had CFOE values comparable to those infants with no severe cerebral injury. LVO and MABP tended to be low or normal in those with HPI (not illustrated) and normal or high in those with PVL (not illustrated).

1. Tsuji M, Saul JP, du Plessis A, et al. Pediatr 2000;106 :625-632.
2. Tyszczuk L, Meek J, Elwell C, Wyatt JS. Pediatr 1998;102:337-341.
3. Yoxall CW, Weindling AM, Dawani NH, Peart I. Ped Res 1995;38:319-323.

Does the fatty acid composition of human platelets differ between neonates and adults and is it related to membrane fluidity?

L.O. Kurlak, T J Stephenson, F Broughton Pipkin
School of Human Development, Queen's Medical Centre, Nottingham, NG7 2UH,U.K.

We have previously shown that membrane fluidity is greater in cord than adult platelets (1). Phospholipid structure incorporates fatty acyl chains which can influence membrane fluidity and function. We investigated whether the fatty acid profile differs between adults and neonates and whether it has an influence on platelet membrane fluidity.

Washed platelets were prepared from adults (n=19),full term umbilical cord (n=52),and snap frozen in liquid N2. Thawed samples were sonicated and extracted using chloroform: methanol (2:1). Phospholipids were separated by differential solvent extraction on Sep-Pak Silica cartridges(2)and their fatty acid methyl esters were identified using Gas Chromatography-Mass Spectrometry. Membrane fluidity was assessed by measurement of fluorescence anisotropy using TMA-DPH and DPH fluorophores.

(n.d. = not detected)

In a subset of neonates (n=28) studied, there was no direct correlation between fatty acid levels and fluorescence anisotropy.

The difference in fatty acid composition in the neonates may reflect the accretion pattern in late pregnancy, when accumulation rates are higher for longer chain fatty acids relative to shorter fatty acids. Total antioxidant capacity increases towards term therefore membrane fluidity may be more affected by increased free radical -induced lipid peroxidation. This may also explain the greater variability in the neonatal samples.
1. Kurlak LO, Stephenson TJ, Broughton Pipkin F. J Physiol 1999;517.P:7P.
2. Hamilton JG, Comai K. Lipids 1988;23(12):1146-1149.

The effects of body shape at birth on the physical and behavioural development of the neonatal pig

J. C. Litten, A. M. Corson, P.C. Drury and L. Clarke
Department of Agricultural Sciences, Imperial College at Wye, University of London, Wye, Ashford, Kent, TN25 5AH, UK.

Introduction Individuals who have undergone perturbations in intrauterine growth often lag behind in both their mental and physical development (1). Recent evidence suggests that body shape may be a more important diagnostic indicator of future health than birth weight alone (2). The objective was to use the piglet to determine whether body shape at birth influences their physical and behavioural development.

Methods Forty-five sow-reared piglets were selected from a population of 160 animals. Individual body weight and crown-to-rump length (CRL) were recorded until weaning (24-28 days) to assess physical development. Piglet response to, and interaction with a ball for 1800 seconds on 3 consecutive days from day 14 of neonatal life was used to calculate a numerical index of behavioural development as follows:

Behavioural developmental index (BDI) = (1800 - Ttime) + (1800 - Mtime).

Ttime = time taken to touch the ball (sec) and Mtime = time taken to move the ball (sec). Ponderal index (PI: body weight /CRL 3: kg/m3) was used to sub-divide the animals into 3 groups: low (<10th percentile), normal (11th-89th percentile) and high (>90th percentile). General Linear Model, ANOVA, was used to assess differences between the groups.

Results Piglets with a PI >90th exhibited faster behavioural development than the other groups (P<0.001) but their total body weight gain was similar. Total body weight gain was reduced in piglets with a PI<10th compared to the normal group (P<0.01).

Values are means±SEM

Conclusion In conclusion, body shape at birth can have a pronounced influence on the physical or behavioural development of newborn piglets during the first few weeks of life but it has yet to be determined whether these differences extend into adulthood or are a reliable model of human development.

Acknowledgements The authors would like to thank Cotswold Pig Development Company for their assistance during this study. J.C.L. also wishes to thank Wye College for the provision of a PhD studentship.

Reference
1. Lucas, W.D., Campbell, B.C. Human Nature. 2000, 11: 1-26.
2. Barker, D. J. P. (1998) In: Mothers, babies and health in later life, 2nd Edition, London, Churchill, Livingstone, pp 50-54.

Clinically relevant oxygen fluctuations combined with elevated carbon dioxide in a rat model of retinopathy of prematurity (ROP).

J.McColm¹, B.Gellen¹, S.Cunningham³, J.Wade¹, K.Sedowofia¹, T.Sharma², N.McIntosh¹, B.Fleck².
Child Life & Health, Edinburgh University¹, Princess Alexandra Eye Pavilion², Royal Hospital for Sick Children³, Edinburgh, Scotland.

Aim: To investigate clinically relevant oxygen fluctuations combined with hypercarbia on the retinal development of newborn rat pups.
Methods: Transcutaneous oxygen data was recorded every minute for 14 days from a preterm infant who developed severe ROP. This data was translated into a profile of inspired O2 values for the rat1. Animals were then exposed to either this variable O2 profile (V) or to this variable O2 profile with constant 5% carbon dioxide (V/CO2). Controls were raised in room air. After sacrifice, retinal wholemounts were prepared and blood vessels visualised with endothelial cell specific lectin. Digital images were taken using confocal microscopy and analysed using Scion Image.
Results: Values are median (interquartile range).

^ap< 0.05, ^bp<0.01, ^cp<0.001 compared to C; ^dp<0.001 V/CO2 vs V. Statistics were a multilevel analysis. atv = abnormal terminal vessels.*n=16
Conclusion: Variations in oxygen alone induced changes in the developing retinal blood vessels of rats similar to changes seen during human retinopathy2. However, when this was combined with continuous CO2 these changes were more severe.

1. McColm JR,.Cunningham S. J Med Engineer Technol 2000;24:45-52.
2. Cunningham S, McColm JR, Wade J, Sedowofia K, McIntosh N, Fleck B. Invest Ophthalmol Vis Sci 2000;41:4275-80.

Effect of maturation on infant diaphragmatic function assessed using a non-volitional test

Rafferty GF, Greenough A, Dimitriou G & Moxham J*

Depts of Child Health and *Respiratory Medicine
Guy's, King's & St Thomas' School of Medicine
King's College Hospital, London, UK

Background: Infant maturation appears to affect diaphragm function, but those data were derived using an effort dependent test which may have biased the results.
Objective: To determine the effect of maturation on diaphragmatic function using a non-volitional test.
Patients: 35 infants (17 born preterm) with a median gestational age of 37 (range 25-42) weeks. At the time of study, their median postconceptional age (PCA) was 39 (range 32-44) weeks, 13 were studied at a PCA of less than 37 weeks. At the time of measurement none had respiratory problems or were hyperinflated (lung volume range 23 to 35 ml/kg).
Methods: Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated by magnetic stimulation of the phrenic nerves. Balloon catheters were positioned in the lower third of the oesophagus and stomach. Oesophageal (Poes) and gastric (Pgas) pressure changes were measured using differential pressure transducers. The pressure signals were amplified and displayed in real time on a computer running Labview software and Pdi derived by online subtraction of Poes from Pgas
Results: The preterm compared to the term infants had significantly lower median right (4.0, range 2.5-6.8 cmH2O versus 4.8, range 2.8-7.2 cmH2O) and median left (3.6, range 2.6-4.8 cmH2O versus 4.3, range 2.7-6.8 cmH2O) transdiaphragmatic pressures (p<0.05). Left and right Pdi correlated significantly with gestational age (r=0.4, p<0.05 and r=0.41, p<0.05 respectively) and PCA (r=0.37, p<0.05 and r=0.55, p<0.01 respectively).
Conclusion: The degree of maturation at birth and the postconceptional age at measurement affects infant diaphragmatic function.

Does TPN Provide Adequate Nutrition during the Transitional Phase in Preterm Infants?

Smith CM1, Coombs RC², Eastell R¹.
¹Bone Metabolism Group, Division of Clinical Sciences (NGHT), University of Sheffield, Sheffield, UK, ²Jessop Wing, Royal Hallamshire Hospital, Sheffield, UK.

Background: Nutrition during the transitional phase (TP) is likely to be an important determinant of weight change (Berry, 1997).
Aim: To investigate the relationship between weight loss and nutrition during TP.
Methods: 49 preterm infants were studied up to discharge. Bodyweight was assessed twice weekly. Daily nutritional intake was estimated using fluid charts.
Results: * denotes p<0.05, ** p<0.01. Median (range) gestational age (GA) and birth weight (BW) were 32 (25 to 35) weeks and 1.62 (0.79 to 2.57) kg respectively. 39 infants (79.6%) received parenteral nutrition. During TP there was a significant mean (SD) reduction of weight SDS of 0.85 (0.34), which was not regained thereafter. Energy and protein intakes were within the Tsang (1993) recommendations. However, there was a proportion of infants whose intakes did not meet the minimum requirements. Using backwards stepwise regression, 30.4%** change in weight SDS was predicted by GA and the time to full oral feeds. Other associations included energy:protein ratio (E:Pr), duration of TPN and use of caffeine (r = -0.33*, -0.47**, -0.27** respectively). Nutrient intakes were negatively associated with duration of parenteral nutrition, with the exception of E:Pr.
Conclusions: The use of PN is an independent contributor to reduction in weight SDS in the TP. The clinical goal of TPN during TP is to maintain homeostasis. However, this goal may be inadequate, since the reduction in weight SDS is not recovered. The use of caffeine may exacerbate weight loss. The clinical goal and nutrient content of transitional parenteral feeding regimens should be reassessed.
References: Berry MA et al 1997 Pediatrics. 100: 640-646.

Prediction of recurrent respiratory symptoms in very preterm infants at follow-up

Thomas M, Greenough A, Johnson A*, Limb E*, Marlow N**, Peacock J*, Calvert S*

Departments of Child Health, King's College Hospital, *St George's Hospital Medical Schools, London and University Hospital, Nottingham, UK

Background: Preterm infants, particularly those born at very early gestations, frequently suffer recurrent cough and wheeze at follow-up.
Aim: To determine whether the chest radiograph (CXR) appearance at 28 days or 36 weeks postconceptional age (PCA) predicted such problems and was a better predictor than readily available clinical data.
Patients: One hundred infants with a median gestational age of 26 weeks (range 23-28) entered into the UKOS trial were studied.
Methods: Chest radiographs taken at 28 days and 36 weeks PCA were assessed using a scoring system for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation. At 6 months of age corrected for prematurity, the occurrence and frequency of cough and wheeze since discharge were determined using a symptom questionnaire.
Results: Seventeen infants were reported to wheeze more than once a week. Compared to those who did not, they had a higher total chest radiograph score at 36 weeks PCA (p<0.05), with higher scores for fibrosis/interstitial shadows (p<0.05) and cystic elements (p<0.01), but had similar chest radiograph scores at 28 days. Gestational age, birthweight, the proportions with a family history of atopy, maternal smoking during or after pregnancy, the duration of ventilation and chronic lung disease status were also similar in the two groups. The 20 infants with cough more than once a week only differed significantly from the rest of the cohort with regard to their higher CXR score for cystic elements at 36 weeks PCA (p<0.05). Construction of receiver operator characteristic curves revealed that the total CXR score at 36 weeks PCA was the best predictor of frequent wheeze.
Conclusion: The CXR appearance at 36 weeks PCA, but not at 28 days, predicts recurrent wheeze at follow-up in very preterm infants more accurately than readily available clinical data.

Mild systemic hypothermia as an emergency treatment for neonatal hyperammonaemic coma.

Andrew Whitelaw , Sarah Bridges, Alison Leaf and David Evans
Neonatal Intensive Care Unit, Southmead Hospital, Bristol BS10 5NB, United Kingdom. andrew.whitelaw@bristol.ac.uk.

In infants with inherited urea cycle disorders, hyperammonaemic coma lasting more than 5 days is always associated with severe neurodevelopmental delay whereas coma lasting less than 3 days may have a good outcome (1). However, catabolism may predominate and high rates of ammonia production may mean that treatments such as haemofiltration, dialysis and metabolite therapy do not lower the plasma ammonia rapidly enough to protect the brain. We hypothesised that mild systemic hypothermia might be protective in this situation by reducing enzymatic production of ammonia and reducing extracellular glutamate (2).
An infant presented at 3 days with hyperammonaemic coma and seizures due to carbamyl phosphate synthetase deficiency. Haemofiltration, alternative pathway metabolites and glucose/insulin failed to lower the plasma ammonia below 2,000 *mol/l. The infant was then cooled to a rectal temperature of 34 o C for 48 hours and again haemofiltered for 12 hours.
Plasma ammonia fell to around 100 *mol/l and remained at this level after haemofiltration. He awoke, breathed spontaneously and resumed bottle feeding.
Hypothermia may be therapeutic in this and possibly other metabolic comas by lowering the enzymatic rate of production of the toxin while non-enzymatic methods remove the toxin.
1. Msall M, Batshaw ML, Suss R. Neurological outcome in children born with inborn errors of urea cycle disorders. N Eng J Med 1984;310:1500
2. Thoresen M, Satas S, Puka-Sundvall M, Whitelaw A, Hallstrom A, Loberg EM, Ungerstedt U, Steen PA, Hagberg H. Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins. Neuroreport 1997 Oct 20; 8: 3359-62

Sonographic determination of spinal canal depth in neonates.

Zubier M1, Kelsall W¹, Tooley J¹.
¹ Neonatal Intensive care unit, Rosie Maternity Hospital, Cambridge.UK

Background The assessment of suspected neonatal infections may require analysis of cerebrospinal fluid (CSF) 1. Up to 50% of CSF samples obtained from newborns can be blood stained and difficult to interpret2. Traumatic blood stained samples are usually due to damage to the venous plexus on the posterior vertebral bodies, when the lumbar puncture (LP) needle is inserted too far. A normogram has been developed for LP needle insertion in children based on height3.
Objective To use ultrasound to measure the depth of the spinal canal (S.C) below the skin, to construct a normogram for LP needle insertion in relation to weight in neonates.
Methods Infants were recruited in the study following admission to the neonatal unit and transitional care wards. After written consent, ultrasound measurements were made with the infant positioned in the curled left lateral position as for LP at the site between L3- L4. Ultrasound scans were performed by 2 investigators using a 6 MHz phase array probe -Toshiba Powervision scanner. Images were frozen and 3 measurements were performed (1) skin to superficial wall of S.C, (2) skin to deep wall of SC and (3) mid point of S.C
Result Scans were performed on 116 newborn infants, median gestational age 34 weeks with range of (24- 42 weeks),and median birth weight 2461grams with range of ( 520- 4610 grams).
Results of spinal canal depth against weight are shown below, the correlation of mid point of spinal canal r = 0.922

Conclusion : There is a clear relationship between weight and spinal canal depth. Use of the normogram could reduce the number of traumatic LP.

References:

1. Hristeva L, Bowler I, Booy R, King A T, Wilkinson A R. Value of CSF Examination in the diagnosis of meningitis in the newborn. Archives of diseases in Childhood 69: 514-517,1993 Nov.
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The effects of maternal protein restriction in late pregnancy on organ development and appetite in the offspring

CB Doherty, CN Hales
University of Cambridge, Department of Clinical Biochemistry, Cambridge, UK

Background: Diet in late pregnancy plays an important role in fetal growth. During the Dutch Hunger Winter, exposure to famine in the last trimester of pregnancy had greater effects on birth weight than exposure during the previous two trimesters1. Famine exposure in late pregnancy also had larger effects on the offspring in middle age in terms of glucose tolerance and weight gain. The mechanistic basis of these programmed effects remains unclear.
Aim: To determine if late pregnancy malnutrition affects a) selective organ growth (suggesting vascular alteration antenatally) and b) appetite in the offspring.
Study Design: Pregnant Wistar rats (n=18) were randomised to receive a) control diet for two trimesters and low protein (8%) diet in the third trimester (late low protein - LLP), b) control diet throughout pregnancy or c) low protein (8%) diet throughout pregnancy (LP). Body and organ weights of the offspring were studied at days 3 and 21 (weaning) postnatally

Results are expressed as mean and standard deviation of the mean. **P<0.01, *P<0.05 (LLP vs Control). ^fff P<0.001, ^ff P<0.01, ^f P<0.05 (LLP vs LP).

At day 3 postnatally body and kidney weights were significantly lower in the late low protein group (LLP) compared with controls and significantly heavier compared with the LP group. Brain weight was significantly heavier in the LLP group versus the control group. By day 21 postnatally body weights were significantly heavier in the LLP group compared with controls. Absolute brain weight was no longer different. Stomach weight (a proxy for appetite ) was significantly heavier in the LLP group compared with both other groups.
Conclusions:
1. Maternal protein restriction in late pregnancy is associated with selective changes in organ weight suggesting alterations in antenatal blood flow.
2. This antenatal diet pattern may be associated with increased appetite in the offspring.
3. Maternal protein restriction in late pregnancy has less of an effect on birth weight than protein restriction throughout pregnancy in this model.

1. Ravelli et al. The Lancet 1998; 351, 173-7