early postnatal blood lactate predicts short-term outcome in infants with perinatal asphyxia

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Discussion: fMRI responses to light in sedated children result in a characteristic negative BOLD response and the increased signal to noise ratio afforded by imaging at 3.0 T provides robust measures of connectivity and functional activation. Combining fMRI and diffusion tractography has the potential to be an effective approach to understanding abnormalities in the brains of preterm infants. References [1] Behrens, et al. Nat Neurosci 2003;6:7507. doi:10.1016/j.earlhumdev.2006.09.022 —————————————————————————————————————————————————————————————— White matter lesions in term infants with neonatal encephalopathy: Correlation with later scans and neurodevelopmental outcome T. Bregant a,b , M. Rutherford c , F. Cowan b a Pediatrics Clinic, Ljubljana, Slovenia b Department of Pediatrics, Imaging Sciences Department, Imperial College London, Hammersmith Hospital, London, UK c Robert Steiner MR Unit, Imaging Sciences Department, Imperial College London, Hammersmith Hospital, London, UK Background: The commonest brain abnormality after perinatal hypoxicischaemia and neonatal encephalopathy (NE) is damage to the basal ganglia (BGT). However there are infants who escape this damage but have abnormally appearing white matter (WM). The long-term outcome of these children has not been well defined. Aim: To evaluate, in term infants with NE and abnormally appearing WM but normal BGT on neonatal MRI scan, the evolution of the scans in the first 12 years and the relation of the imaging findings to neurodevelopmental outcome at 24 years. Subjects/Methods: From a cohort of 270 term infants with perinatal asphyxia and NE (without evidence of systemic infection, a metabolic, or a congenital disorder), born at or referred to the Hammersmith Hospital, London (19912000) 46 infants had normally appearing BGT but abnormal WM on neonatal scans; 18 infants had normal scans. Follow-up scans were obtained in 57 infants. Griffiths developmental scales, standardized neurological examination and HC, evidence of cerebral palsy (CP), visual, hearing, language, feeding and behavioural problems) was obtained in all infants. Parental and ethical permission from the Hammer- smith Hospital REC was obtained. Results: Median (range) of gestation was 40.1 weeks (3642 weeks), birth weight 3.26 kg (2.04.82 kg), head circumference (HC) 35.0 cm (3139.1 cm), Apgar scores at 1/5 min was 2 (09)/6 (010), pH 6.97 (6.567.37). 38 infants (59%) were male; 26 had Sarnat stage I and 38 had stage II NE. WM abnormality on neonatal scans was mild in 20, moderate in 14, severe in 9 and severe with haemorrhage in 3; 18 infants had normal scans. Follow up scans were normal in 18, mildly abnormal in 18, moderate in 9, severe in 8 and severe with marked tissue loss in 4. Neonatal and later grading of scans remained the same 67%; improved in 12% and deteriorated in 21% by one grade. There was no difference in the perinatal data bar HIE staging between the infants in the different WM groupings at birth or follow-up. Mean (range) DQ at a median age of 3 years in children with normal WM was 109 (88125), with mild WM 106 (85124), moderate WM 88 (40126), severe WM 71 (4595) severe with haemorrhage 50 (4060). In contrast, the neurological exam score was only low in the severe WM group. Six children had CP but only two were not independently ambulant. Follow- up scan abnormalities included a PVL-like appearance, reduced thalamic size and cortical abnormality. The more severe follow up scans were associated with CP, poor head growth, early feeding problems, language delay, squint and behavioural difficulties. Discussion: Follow-up scans of infants with NE show that neonatal WM abnormality may lead to significant long-term problems. Early and late scans correlate but the change in grading in 33% suggests that external factors may influence outcome. Outcome at 24 years can be significantly abnormal in those with moderate and severe scan abnormality. Despite few major motor problems these infants require prolonged follow up and considerable support [1]. Reference [1] Marlow N, et al. Arch Dis Child 2005;90:F3807. doi:10.1016/j.earlhumdev.2006.09.023 —————————————————————————————————————————————————————————————— Early postnatal blood lactate predicts short-term outcome in infants with perinatal asphyxia Sanjeev Deshpande Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ, UK Background: Early identification of infants at risk of serious brain injury following perinatal asphyxia is of utmost importance for targeting neuroprotective therapies. Aim: To assess the ability of first postnatal blood lactate concentration to predict the short-term outcome (death or moderate to severe neonatal encephalopathy) in babies with perinatal asphyxia. Methods: I reviewed the case records of all consecutive babies of 36 weeks' gestation with 5-min Apgar score of 6 and needing positive pressure ventilation for resuscitation and admission to the neonatal unit between 1999 and 2003. Babies with major congenital malformations and chromoso- mal abnormalities were excluded. Neonatal encephalopathy was staged using the Sarnat and Sarnat classification. MannWhitney U test was used for comparison of continuous data whilst receiver operating characteristic (ROC) curves were used to determine the sensitivity, specificity, and positive and negative predictive values for prediction of the adverse outcome. The study was approved by the Shropshire research ethics committee. Results: Blood lactate concentrations during the first 3 h after birth were available for 84/116 (72%) of eligible infants. Their mean (S.D.) gestational age and birth weight were 39.7 weeks (1.4 weeks) and 3483 g (568 g), respec- tively. Their median (IQR) 1- and 5-min Apgar scores were 2 (13) and 5 (46), respectively, with median (IQR) age at onset of regular respirations being 10 min (615 min). Severe acidosis (pH < 7.0 and/or base excess ≤− 16 mmol/l in cord 128 Abstracts

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Discussion: fMRI responses to light in sedated childrenresult in a characteristic negative BOLD response and theincreased signal to noise ratio afforded by imaging at 3.0 Tprovides robust measures of connectivity and functionalactivation. Combining fMRI and diffusion tractography hasthe potential to be an effective approach to understandingabnormalities in the brains of preterm infants.References[1] Behrens, et al. Nat Neurosci 2003;6:750–7.

doi:10.1016/j.earlhumdev.2006.09.022——————————————————————————————————————————————————————————————

White matter lesions in term infants with neonatalencephalopathy: Correlation with later scans andneurodevelopmental outcome

T. Breganta,b, M. Rutherfordc, F. Cowanb

aPediatrics Clinic, Ljubljana, SloveniabDepartment of Pediatrics, Imaging Sciences Department,Imperial College London, Hammersmith Hospital,London, UKcRobert Steiner MR Unit, Imaging Sciences Department,Imperial College London, Hammersmith Hospital,London, UK

Background: The commonest brain abnormality afterperinatal hypoxic–ischaemia and neonatal encephalopathy(NE) is damage to the basal ganglia (BGT). However thereare infants who escape this damage but have abnormallyappearing white matter (WM). The long-term outcome ofthese children has not been well defined.Aim: To evaluate, in term infants with NE and abnormallyappearing WM but normal BGT on neonatal MRI scan, theevolution of the scans in the first 1–2 years and the relationof the imaging findings to neurodevelopmental outcome at2–4 years.Subjects/Methods: From a cohort of 270 term infants withperinatal asphyxia and NE (without evidence of systemicinfection, a metabolic, or a congenital disorder), born at orreferred to the Hammersmith Hospital, London (1991–2000)46 infants had normally appearing BGT but abnormal WM onneonatal scans; 18 infants had normal scans. Follow-upscans were obtained in 57 infants. Griffiths developmentalscales, standardized neurological examination and HC,evidence of cerebral palsy (CP), visual, hearing, language,feeding and behavioural problems) was obtained in allinfants. Parental and ethical permission from the Hammer-smith Hospital REC was obtained.Results: Median (range) of gestation was 40.1 weeks (36–42 weeks), birth weight 3.26 kg (2.0–4.82 kg), headcircumference (HC) 35.0 cm (31–39.1 cm), Apgar scores at1/5 min was 2 (0–9)/6 (0–10), pH 6.97 (6.56–7.37). 38 infants(59%) were male; 26 had Sarnat stage I and 38 had stage II NE.WM abnormality on neonatal scans was mild in 20, moderatein 14, severe in 9 and severe with haemorrhage in 3; 18infants had normal scans. Follow up scans were normal in 18,mildly abnormal in 18, moderate in 9, severe in 8 and severewith marked tissue loss in 4. Neonatal and later grading ofscans remained the same 67%; improved in 12% anddeteriorated in 21% by one grade. There was no difference

in the perinatal data bar HIE staging between the infants inthe different WM groupings at birth or follow-up. Mean(range) DQ at a median age of 3 years in children with normalWM was 109 (88–125), with mild WM 106 (85–124), moderateWM 88 (40–126), severe WM 71 (45–95) severe withhaemorrhage 50 (40–60). In contrast, the neurological examscore was only low in the severe WM group. Six children hadCP but only two were not independently ambulant. Follow-up scan abnormalities included a PVL-like appearance,reduced thalamic size and cortical abnormality. The moresevere follow up scans were associated with CP, poor headgrowth, early feeding problems, language delay, squint andbehavioural difficulties.Discussion: Follow-up scans of infants with NE show thatneonatal WM abnormality may lead to significant long-termproblems. Early and late scans correlate but the change ingrading in 33% suggests that external factors may influenceoutcome. Outcome at 2–4 years can be significantly abnormalin those with moderate and severe scan abnormality. Despitefew major motor problems these infants require prolongedfollow up and considerable support [1].Reference[1] Marlow N, et al. Arch Dis Child 2005;90:F380–7.

doi:10.1016/j.earlhumdev.2006.09.023——————————————————————————————————————————————————————————————

Early postnatal blood lactate predicts short-termoutcome in infants with perinatal asphyxia

Sanjeev Deshpande

Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ, UK

Background: Early identification of infants at risk of seriousbrain injury following perinatal asphyxia is of utmostimportance for targeting neuroprotective therapies.Aim: To assess the ability of first postnatal blood lactateconcentration to predict the short-term outcome (death ormoderate to severe neonatal encephalopathy) in babieswith perinatal asphyxia.Methods: I reviewed the case records of all consecutivebabies of ≥36 weeks' gestation with 5-min Apgar score of ≤6and needing positive pressure ventilation for resuscitationand admission to the neonatal unit between 1999 and 2003.Babies with major congenital malformations and chromoso-mal abnormalities were excluded. Neonatal encephalopathywas staged using the Sarnat and Sarnat classification. Mann–Whitney U test was used for comparison of continuous datawhilst receiver operating characteristic (ROC) curves wereused to determine the sensitivity, specificity, and positiveand negative predictive values for prediction of the adverseoutcome. The study was approved by the Shropshireresearch ethics committee.Results: Blood lactate concentrations during the first 3 hafter birth were available for 84/116 (72%) of eligibleinfants. Their mean (S.D.) gestational age and birth weightwere 39.7 weeks (1.4 weeks) and 3483 g (568 g), respec-tively. Their median (IQR) 1- and 5-min Apgar scores were 2(1–3) and 5 (4–6), respectively, with median (IQR) age atonset of regular respirations being 10 min (6–15 min). Severeacidosis (pH<7.0 and/or base excess≤−16 mmol/l in cord

128 Abstracts

or first postnatal blood gas) was found in 41 (49%) infants.Moderate to severe encephalopathy developed in 28 (33%)and 10 (11.9%) infants, respectively; all with severeencephalopathy died.

First postnatal blood lactate concentrations, measured ata median (IQR) age of 65 min (38–119 min), ranged from 0.5to 42.7 mmol/l. All infants with first lactate of <12 mmol/lsurvived but 24% of those with values above this died.Median (IQR) first postnatal blood lactate concentration wassignificantly higher among infants with moderate to severeencephalopathy than among those with no or mild encepha-lopathy [19 (14.6–22) vs. 8.4 (5.22–12.5); p<0.0001]. Bloodlactate concentration showed similar discriminating abilityfor prediction of moderate to severe encephalopathy as thefirst postnatal pH or base excess [area under ROC curve –0.88 (S.E.=0.04), 0.78 (S.E.=0.06) and 0.82 (S.E.=0.06),respectively}. The sensitivity, specificity, positive andnegative predictive values of first postnatal blood lactateconcentration of ≥12 mmol/l for moderate to severeencephalopathy were 92%, 67%, 58% and 95%, respectively,the corresponding values for a composite predictor (5-minApgar score≤5, or pH<7.0, or base excess≤−16 mmol/l)being 93%, 39%, 43% and 92%, respectively. Lactateconcentration of ≥12 mmol/l correctly classified 75% ofinfants compared to 57% when the composite predictor waspresent.Conclusions: Elevated blood lactate concentration duringthe first 3 h after birth is a significant predictor of moderateto severe encephalopathy, similar to that reported by Shahet al. [1]. The relationship between early hyperlactatemiaand long-term neurodevelopmental outcome remains to bedetermined.Reference[1] Shah S, et al. J Perinatol 2004;24:16–20.

doi:10.1016/j.earlhumdev.2006.09.024——————————————————————————————————————————————————————————————

Perinatal palliative care or termination ofpregnancy after prenatal diagnosis of lethal fetalabnormality

A.C.G. Breezea, C.C. Leesa,*, A. Kumarb,H.H. Missfelder-Lobosa, E.M. Murdochb

aDivision of Maternal–Fetal Medicine, Box 228,Addenbrooke's Hospital, Hills Road,Cambridge, CB2 2QQ, UKbNeonatal Intensive Care Unit, Box 226,Addenbrooke's Hospital, Hills Road,Cambridge, CB2 2QQ, UK

Objectives: To determine timelines, outcomes and parentaldecision-making when a diagnosis of lethal fetal abnormalityis made, and establish basic principles for ‘perinatalpalliative care’ an alternative to termination.Methods: This was a prospective observational audit andethical approval was not by the LREC. The population waswomen referred to fetal medicine centre after 18 weeks ofgestation, in which a diagnosis of one of three categories oflethal fetal abnormality was made. Data were collectedprospectively in cases where a diagnosis of lethal abnorm-

ality was made. The main outcome measures were: theproportion of women who chose to continue the pregnancy;time to specialist confirmation of lethal abnormality; timeto decision following initial referral; time to neonataldeath if baby was live born; and the proportion consentingto post-mortem.Results: The time to specialist confirmation followinginitial ultrasound was up to 14 days (median of 6 days),and from specialist confirmation of lethality to decision onterminating or continuing the pregnancy was up to 8 days(median of 1.5 days). In 8 of 20 cases, the parentscontinued with their pregnancy. Two babies were stillbornand the six live born babies lived for 1 h to 21 days (medianof 1 day).Conclusion: About 40% of parents faced with a diagnosis oflethal fetal abnormality chose to continue their pregnancies.The time taken for referral, specialist investigation anddecision-making may be over 2 weeks. The majority of babieswhere parents chose to continue the pregnancy were liveborn, however no nationally agreed guidelines nor resourcesfor ‘perinatal palliative care’ of these babies exist.References[1] Statham HE. Fetal Matern Med Rev 2002;13(4):217–47.[2] Leuthner SR. Pediatr Clin N Am 2004;51:747–59.[3] Royal College of Obstetricians and Gynaecologists (GreatBritain). Ethics Committee. London: RCOG Press; 1998.

doi:10.1016/j.earlhumdev.2006.09.025——————————————————————————————————————————————————————————————

A short trial of endotracheal CPAP to predictextubation success

C.O.F. Kamlin1, P.G. Davis1,2, B. Faber1, B. Mills1,C.J. Morley1,2,3

1Royal Women’s Hospital Melbourne2University of Melbourne3Murdoch Children’s Research Institute

Background The adverse effects of prolonged endotrachealintubation on the preterm infant include sepsis, subglotticinjury and bronchopulmonary dysplasia. A spontaneousbreathing trial (SBT) has been shown to have a high positivepredictive value (PPV) for predicting extubation success ininfants <1250 g judged ready for extubation1.Aims To use the SBT prospectively during the weaning ofpreterm infants from ventilation to determine their readi-ness for extubation.Methods Ventilated infants with a birth weight ≤1750 gwere eligible and the study was approved by the localresearch and ethics committee. The SBT was applied onward rounds when either the entry criteria were met(ventilator rate ≤40 bpm, volume guarantee [VG] tidalvolume (VTe) set at ≤4.5 ml/kg and FiO2 =40%) or when theclinician considered the infant ready for extubation. TheSBT involved switching the ventilator mode to endotrachealcontinuous positive airway pressure (PEEP of 6 cm H2O) forup to 3 minutes. The infant’s heart rate and oxygensaturation were observed. The test was discontinued(failed) if the infant had either a bradycardia (<100 bpm)or desaturation (<85% after baseline FiO2 was increased by

129Abstracts