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Perinatal medicine

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G28 LONGITUDINAL CHANGE IN LACTATE, PH, AND BASE EXCESS IN BLOOD FROM CLAMPED AND UNCLAMPED UMBILICAL CORD VESSELS

L. Armstrong, B. Stenson.The Simpson Centre for Reproductive Health, Edinburgh, UK

Introduction: Umbilical cord lactate is a clinically useful prognostic marker of neurological morbidity. Umbilical cord samples are often delayed, or taken from placental vessels, yet there are no data on how this practice may affect lactate measurement. We studied the effect of delayed sampling in vessels isolated from (clamped), and in continuity with the placenta (unclamped).

Methods: Umbilical cords of placentas obtained immediately after delivery were clamped at five locations. Paired samples were taken from clamped and unclamped vessels at 0, 20, 40, and 60 minutes, and analysed for lactate, pH, PCO2, and BE. Data were analysed as change from time 0 at 20, 40, and 60 minutes.

Results: n = 38. Lactate was higher than at time zero after 20 minutes in both clamped (p<0.001) and unclamped vessels (p = 0.005). pH is unchanged over 60 minutes in clamped vessels (p = 0.54) but reduces in linear fashion in unclamped vessels (p<0.001), see fig 1. Base excess widened in both clamped and unclamped vessels by 20 minutes (p<0.05). Venous and arterial blood had similar findings. Change in unclamped vessels was greater than in clamped vessels.

Figure 1

 Mean Δ arterial lactate and pH (±2SD) over 60 minutes, in clamped (solid bars) and unclamped (dotted bars) vessels.

Conclusion: Obstetric guidelines state that blood from doubly clamped cord vessels can be reliably sampled for pH and blood gases upto one hour after delivery. Our study shows that cord blood continues to undergo anaerobic glycolysis, and is thus unreliable for lactate and base excess after only 20 minutes, even if the vessel has been doubly clamped. Delayed sampling from unclamped vessels is unreliable for all measurements. Fetal metabolic acidosis has important clinical and medico-legal implications. Guidelines should reflect these findings to avoid serious misinterpretation of cord blood analysis.

G29 ABNORMAL ANTENATAL UMBILICAL DOPPLERS: AN INDEPENDENT RISK FACTOR FOR EARLY ONSET NEONATAL NECROTISING ENTEROCOLITIS IN PRETERM BABIES

V. Kamoji, J. Dorling, D. Field, ElDraper, B. Manktelow.Leicester Royal Infirmary, Leicester, UK

Aim: This study tested the hypothesis that preterm babies born to mothers with abnormal antenatal umbilical Dopplers (absent or reversed end diastolic flow—AREDF), that is, exposed to antenatal gut ischaemia, are at an increased risk of developing necrotising enterocolitis (NEC).

Methods: All preterm ⩽32+6 week gestation babies with no congenital anomaly born to mothers resident in the county of Leicestershire in UK in 2001 and 2002 were identified using the Trent neonatal survey. Clinical data including the presence and severity of any NEC (for the first six weeks for babies <29+6/40, and four weeks for >30 weeks) were extracted from the notes.

Results: 243 preterm babies who met the criteria were identified during the period. Complete data were available for 206 of these babies. A strong correlation between AREDF and the subsequent development of NEC was noted in these babies OR = 5.88 (95% CI 2.41 to 14.34) p<0.0001. This association still held after adjustment for gestational age at birth (odds ratio = 7.64; 95% CI 2.96 to 19.70: p<0.0001) and after adjustment for birth weight for gestational age z-score1 (odds ratio = 6.72; 95% CI 2.23 to 20.25: p = 0.0007).

Conclusions: This study, based on a geographically defined neonatal cohort, indicates that AREDF is an important independent risk factor for the production of early onset NEC in the preterm population.

G30 REDUCED FRACTIONAL ANISOTROPY IN THE POSTERIOR PERIVENTRICULAR WHITE MATTER RELATES TO IMPAIRED VISUAL PERCEPTION IN PRETERM INFANTS AT 6 YEARS OF AGE

L. Dyet1, R. Rathbone1, S. J. Counsell1, J. Allsop1, J. Fitzpatrick1, E. Isaacs2, M. Rutherford1, A. D. Edwards1, F. Cowan1.1Imperial College, London, UK; 2Institute of Child Health, London, UK

Background: Visuospatial abnormalities are common in the ex-preterm population and may contribute to fine motor difficulties.

Objective: To investigate relationships between fractional anisotropy (FA) within the white matter and neuropsychological outcome in preterm infants at 6 years of age.

Methods: Preterm infants born at <30 weeks gestational age had neuropsychological testing (WPPSI-R, NEPSY) and 3 Tesla brain diffusion tensor imaging (DTI) at 6 years of age. Ethical approval was granted and informed consent was obtained in each case. Regions of interest were placed within the white matter of the anterior, central, and posterior centrum semiovale and in the frontal and posterior periventricular regions.

Results: Twenty four children had DTI and WPPSI-R performed at 6 years of age. 18 children also had the NEPSY. A lower WPPSI-R performance IQ was significantly related to FA in both the right (p = 0.022; r2 = 0.23) and left (p = 0.018; r2 = 0.24) posterior periventricular white matter. Significance remained when adjustments were made for gestational age, gender, and age at scan. No significant relationship was found with WPPSI-R verbal IQ. A reduced NEPSY visuospatial subscale score was also significantly related to FA in the right (p = 0.015; r2 = 0.33) and left (p = 0.035; r2 = 0.26) posterior periventricular white matter. When adjustments were made for gestational age, gender and age at scan the relationship on the right side remained significant (p = 0.026), but on the left it did not (p = 0.075).

Conclusion: Microstructural abnormalities in the posterior periventricular white matter are associated with visuospatial abnormalities in preterm infants at 6 years of age.

G31 PACKED CELL TRANSFUSION AND BLOOD FLOW TO THE INTESTINE OF PREMATURE BABIES: EFFECT OF PATENT DUCTUS ARTERIOSUS

S. Gupta, J. P. Wyllie, D. Plews.The James Cook University Hospital, Middlesbrough, Cleveland, UK

Aim: The aim of this study was to assess the effect of blood transfusion on left ventricular output (LVO), superior vena cava (SVC) flow, and superior mesenteric artery (SMA) flow in preterm babies.

Methods: The LVO, SVC flow, SMA flow, and patency of the Ductus arteriosus (PDA) were evaluated using standard echocardiographic and Doppler techniques in preterm babies <30 weeks’ gestation transfused with 10 ml/kg of packed red blood cells. The measurements were performed four hours before (B4), four hours after (A4), and 24 hours post transfusion (A24). A total of 23 transfusions were studied by a single investigator and the data were analysed using the paired t test and Wilcoxan signed rank test. The study was approved by the Institutional Review Board and written informed consent was obtained from parents.

Results: The SMA flow decreased with a concomitant decrease in LVO and increase in SVC flow at four hours post transfusion. The effect was more marked in babies with PDA with a 17% fall in SMA flow. At 24 hours after transfusion the SVC and SMA flow returned to pretransfusion levels (see table).

Abstract G29 Stage of NEC by doppler status

Conclusions: Blood transfusion decreases mesenteric flow with a concomitant increase in SVC flow at four hours post transfusion. The effect on mesenteric flow was more striking in the presence of a PDA. These findings raise the possibility of blood transfusion as an independent risk factor for the development of necrotizing enterocolitis in preterm babies with a PDA.

G32 STANDARDS OF POSTNATAL CARE IN BABIES OF MOTHERS WITH PREGESTATIONAL DIABETES IN ENGLAND, WALES, AND NORTHERN IRELAND IN 2002/03

D. Acolet, K. Fleming, J. Bailey, M. Macintosh, J. Hawdon.CEMACH Central Office, London, UK

Background/Aim: The last national survey of maternity services for women with diabetes was carried out in 1994 by a group commissioned by the St Vincent Taskforce, the Pregnancy and Neonatal Care Group. It showed many organisational deficiencies and in particular a significant proportion of units (44%) still routinely admitting babies of mothers with diabetes to a neonatal unit without a specific medical indication. The current national Diabetes Project aims to build up a national picture of organisational facilities, care, and outcomes for diabetic pregnancies and to make national recommendations. We report on early neonatal care for infants of diabetic mothers.

Methods: Design: Descriptive population based study. Population: 3808 pregnancies in women with pre-gestational diabetes (type 1 and 2) delivering or booking from 01/03/2002 to 28/02/2003 (n = 3451 live births). Data collection: By health professionals in 231 maternity units using a structured questionnaire and a series of neonatal national standards (SIGN guidelines, Diabetes NSF).

Results: Overall admission rate to a neonatal unit was 56% (general UK population: 10%). A third (32.6%) of term babies was admitted to a neonatal unit for special care. More than two thirds of term admissions to a neonatal unit for special care after delivery were potentially avoidable: (a) 26% were admitted for no specific medical reason other than being an infant of mother with diabetes, and (b) 42% of them were admitted for a clinical condition that could have been possibly managed in a mother baby rooming-in environment. More term infants born to mothers with type 1 diabetes were admitted compared to those of mothers with type 2 diabetes (rate ratio = 1.18, 95% CI (1.06 to 1.31), p = 0.002). Babies may have had their first glucose measurement too soon (44% of term infants tested within the first hour). 11% of all term infants were given supplemental feed or glucose based on local routine practice and not clinical indication. Optimal blood glucose testing method was used in only a minority of cases (less than one third). 53% of women intended to breastfeed. This compares with an initial breastfeeding rate of 69% in the general population.

Conclusion: These findings have important implications for the postnatal care of infants of mothers with diabetes. A focused neonatal enquiry is now being set up to understand these observations and provide practice recommendations.

Abstract G32 Transfusion and hemodynamics (mean (SD))

G33 A PROSPECTIVE RANDOMISED DOUBLE BLIND COMPARISON OF O.5% VERSUS 0.05% AQUEOUS CHLORHEXIDINE FOR SKIN ANTISEPSIS PRIOR TO LINE INSERTION IN NEONATES

C. Lilley, A. Powls, A. Gray.Princess Royal Maternity, Glasgow, UK

Background: Effective skin antisepsis prior to line insertion in neonates is important. Reports of skin damage with alcohol and iodine based products have led to aqueous chlorhexidine solutions being used more widely on neonatal units with no published evidence of the safest or most effective concentration.

Aim: To compare the efficacy of the two least concentrated aqueous chlorhexidine solutions on neonatal skin.

Methods: We conducted a prospective randomised controlled double blind clinical trial over a 21 month period on infants greater than 24 hours of age and who required cannulation. Infants were assigned prior to intravenous or arterial cannulation and following informed consent, to a specially prepared hidden label pre-randomised solution of either 0.5% (Group A) or 0.05% aqueous chlorhexidine solution (Group B) on one occasion only. Skin surface swabs were taken before and after cleaning of the skin. Pre- and post-cleaning skin swab results were categorised as cleared, partially cleared, and unchanged using a semiquantitative assay. Adverse skin reactions were logged. Groups were compared with Pearson’s χ2 test. Pre-study power calculations gave a sample size of 24 for each group to detect a 33% difference (power 80%, significance 5%).

Results: Eighty five babies were recruited to the trial. The 41 babies in group A and the 44 babies in group B did not differ significantly in terms of gestation (mean 29.6 weeks, SD 3.78, range 23–41 weeks), weight (mean 1462 g, SD 650, range 650–3790 g) or age of recruitment (mean 8.2 days, SD 6.7, range 2–36 days). Data were not available in three cases for each group and negative swabs prior to cleaning were not included in the final analysis giving a sample size of 26 for each group. 0.5% aqueous chlorhexidine gave significantly better total clearance of bacteria than 0.05% chorhexidine (92% v 38%, p = 0.002; OR 19.2 (95% CI (3.71 to 99.45), p<0.001). Where swabs remained positive after cleaning there was no reduction in bacteria on quantitative analysis in seven (29%) cases in group B. All swabs in group A were either cleared or reduced in bacterial load.

Conclusion: The authors strongly advocate the use of 0.5% over 0.05% aqueous chlorhexidine for skin antisepsis in the neonatal unit. Further studies comparing the efficacy and safety of higher concentrations of aqueous chlorhexidine up to and including 4% are warranted.

G34 DEATH FROM MATERNALLY ACQUIRED INFECTION: A 24 YEAR POPULATION BASED STUDY

N. Embleton, M. Ezzat.Royal Victoria Infirmary, Newcastle upon Tyne, UK

Background: Infection is a potentially preventable cause of perinatal mortality. Large scale population based study is required as it remains relatively rare and single centre series may introduce bias that is difficult to quantify. Widespread efforts at prevention in North America have resulted in a decrease in the incidence of early onset group B streptococcal sepsis, but this has not been widely adopted in the UK. There are also data suggesting an associated increase in early onset gram negative infections with more widespread intrapartum antibiotic usage. In addition, whilst diagnostic criteria for sepsis vary, death from infection may be more robustly defined.

Objective: To document the incidence of death from maternally acquired infection in babies ⩾24 weeks completed gestation, the organisms responsible and any changes in incidence during the period 1981–2004.

Design/Methods: Fetal, neonatal and infant deaths were ascertained for the northern region of England, UK. Cases were identified using a previously well validated population based database of all perinatal death. Original case notes were reviewed afresh. Infection was assumed to be maternally acquired where this resulted in death prior to delivery, when the onset of symptoms was in the first 48 hours of life, or for viral infections presenting in the first 10 days of life that were likely to have been acquired prior to delivery.

Results: There were over 860 000 births in the 24 year survey. During this period there were 350 deaths ⩾24 weeks gestation attributed to maternally acquired infection of which 216 were liveborn. In only 15% of those liveborn could the responsible organism not be precisely identified. No case of death from listeria in liveborn babies was noted in the last 8 year period.

Conclusion: Although the overall rate of maternally acquired infectious death has remained relatively constant, deaths from group B streptococcus have decreased in the last 8 years. This has not been associated with an increase in gram negative organisms.

Abstract G34 Incidence (95% CI) of infectious death per 10 000 births

G35 THE NATURAL HISTORY OF BRAIN MRI ABNORMALITIES IN A PRETERM POPULATION: BIRTH TO 2 YEARS CORRECTED AGE

L. Dyet, N. Kennea, S. J. Counsell, J. Allsop, S. Laroche, F. Cowan, A. D. Edwards, M. Rutherford.Imperial College, London, UK

Background: Very few studies of brain MRI abnormalities in preschool children born preterm have been reported and there is no published longitudinal data from birth until 1 or 2 years of age.

Objective: To perform a longitudinal cohort study investigating the natural history of neonatal brain MRI abnormalities from birth until 2 years corrected age.

Methods: A cohort of infants born at <30 weeks gestational age had serial brain MRI scans between birth and “term” equivalent age and scans at 1 and 2 years corrected age. Ethical approval was granted and informed consent was obtained. Qualitative analysis of neonatal images was performed by two investigators with a third investigator blinded to previous findings analysing later images. Inter and intraobserver variability was calculated.

Results: Fifty eight infants had neonatal, “term”, and 1 year imaging. 46 infants also had 2 year imaging. IVH was associated with thinning of the whole corpus callosum and reduced cerebellar size at 1 year. Neonatal punctate white matter lesions were associated with moderate/severe increased signal intensity within the PPVWM. Ventricular dilatation at “term” was associated with moderate/severe ventricular dilatation, thinning of the whole corpus callosum and white matter atrophy at 1 year. Diffuse excessive high signal intensity (DEHSI) at “term” predicted severe white matter abnormalities with a sensitivity of 1.0 and a specificity of 0.54. There were no significant differences between findings at 1 and 2 years corrected age.

Conclusion: MRI abnormalities during the neonatal period predict persisting abnormalities in brain structure. The absence of DEHSI at “term” predicts normal white matter imaging at 1 year.

G36 IS PVL A GENETIC DISEASE? GENE POLYMORPHISMS AND THE DEVELOPMENT OF CYSTIC PERIVENTRICULAR LEUKOMALACIA

M. Levene, N. Gopichandran, N. Orsi, U. Ekbote, N. Simpson.Department of Paediatrics, Obstetrics and Gynaecology, University of Leeds, Leeds, UK

Background: Cystic periventricular leukomalacia (cPVL) is an important predictor of infants who will subsequently develop cerebral palsy. There is increasing evidence of a causal link between cPVL and perinatal infection, particularly chorioamnionitis.

Aims: To determine susceptibility of very preterm infants to cystic periventricular leukomalacia (cPVL) by investigating the relationship of the condition to genetic carriage of functional cytokine gene single nucleotide polymorphisms (SNPs).

Methods: Extraction of DNA from cord blood or Guthrie cards was undertaken in 228 babies <32 weeks gestation. Cytokine genotypes for SNPs in genes coding for TNF-α, IL-1β, IL-6, IFN-γ, and IL-6 were determined. The correlation of variant allele carriage was compared between babies who developed cPVL on ultrasound examination and those who did not.

Results: Eighteen babies developed cPVL compared with 210 who did not. There was a significantly higher frequency of the C-allele for IL-6 (OR 2.06, CI 1.04 to 4.10) and a significantly lower allele frequency of the A-allele for IFN-γ (OR 0.47 CI 0.24 to 0.95) in the infants who developed cPVL. Infants homozygous for the high secreting A-allele for TNF-α (OR 4.95, CI 1.30 to 19.30) and for the C-allele of IL-6 (OR 5.27 CI 1.91 to 14.54) were significantly more likely to develop cPVL and infants homozygous for the high secreting A-allele of IFN-γ were less likely to develop cPVL (OR 0.23 CI 0.06 to 0.92).

Conclusions: Genetic susceptibility of the fetus/newborn may be a very important factor in determining which infants develop white matter disease following preterm birth. It is probable that environmental factors recognised for the development of cPVL such as chorioamnionitis may have an enhanced effect in genetically predisposed infants.

G37 CARDIOVASCULAR AND METABOLIC MORBIDITY RELATED TO CHORIONICITY AND ANTENATAL INTERVENTION FOR TWIN-TWIN TRANSFUSION SYNDROME

K. Mpenge, K. Sylvester, K. Spencer, K. Nicolaides, A. Greenough.Division of Asthma, Allergy & Lung Biology, King’s College London, London, UK

Background: Twin-twin transfusion syndrome (TTS) occurs in monochorionic twins, survivors have discordant growth and are at increased risk of cardiovascular and renal abnormalities. Reduced birthweight has been associated with metabolic problems in childhood and later life. Endoscopic laser coagulation of vascular anastomoses has been reported to improve survival and reduce neurological complications at six months in monochorionic twins with TTS

Objective: To test the hypothesis that cardiovascular and metabolic outcome in monochorionic twins who have received laser surgery (MC-laser) for severe TTS will be similar to that of dichorionic (DC) twins and monochorionic (MC) twins who have required no intervention.

Methods: Sixty seven women with twin pregnancies cared for in a single centre were enrolled into the study. Perinatal and neonatal data were collected and at one year surviving twins underwent physical examination including blood pressure (BP) and echocardiographic assessment, ultrasonographic determination of renal volume and estimation of cholesterol and cortisol levels.

Results: Multivariate analysis demonstrated significant differences between the groups according to chorionicity and antenatal intervention after accounting for gestational age, birth centile and gender. The MC groups were lighter at follow up (p = 0.006). The MC-laser group had a higher mean systolic BP than the other two groups (p = 0.05). The MC-laser compared to the other groups had, on echocardiographic examination, significantly different tricuspid blood flow velocities (p = 0.01) and pressure gradients (p = 0.02) and, on ultrasound examinations, significantly different renal volumes (p = 0.01). In addition, cholesterol (p = 0.004) and cortisol (p = 0.06) levels were higher in the MC-laser than the other groups.

Conclusion: The magnitude of cardiovascular and metabolic morbidity in monochorionic twins is increased according to the severity of twin-twin transfusion syndrome. These results suggest laser coagulation therapy for TTS, although reported to improve survival, may not improve long term outcome.

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