Papers by Andrew Whitelaw
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2014
Trial design A randomised, parallel group, pragmatic trial. Setting A large UK maternity hospital... more Trial design A randomised, parallel group, pragmatic trial. Setting A large UK maternity hospital. Participants Term infants <2 weeks old with a mild or moderate degree of tongue-tie, and their mothers who were having difficulties breastfeeding. Objectives To determine if immediate frenotomy was better than standard breastfeeding support. Interventions Participants were randomised to an early frenotomy intervention group or a 'standard care' comparison group. Outcomes Primary outcome was breastfeeding at 5 days, with secondary outcomes of breastfeeding selfefficacy and pain on feeding. Final assessment was at 8 weeks; 20 also had qualitative interviews. Researchers assessing outcomes, but not participants, were blinded to group assignment. Results 107 infants were randomised, 55 to the intervention group and 52 to the comparison group. Five-day outcome measures were available for 53 (96%) of the intervention group and 52 (100%) of the comparison group, and intention-to-treat analysis showed no difference in the primary outcome-Latch, Audible swallowing, nipple Type, Comfort, Hold score. Frenotomy did improve the tongue-tie and increased maternal breastfeeding self-efficacy. At 5 days, there was a 15.5% increase in bottle feeding in the comparison group compared with a 7.5% increase in the intervention group.
The Journal of Pediatrics, 2010
Yearbook of Neonatal and Perinatal Medicine, 2008
OBJECTIVE. The goal of this study was to evaluate the role of factors that may determine the effi... more OBJECTIVE. The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy.
New England Journal of Medicine, 2009
Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxia... more Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.
Pediatric Research, 1999
Background: Mild hypothermia (HT) starting after hypoxia-ischemia (HI) is neuroprotective in pigl... more Background: Mild hypothermia (HT) starting after hypoxia-ischemia (HI) is neuroprotective in piglets who are anaesthetized during HT. In the 7 day old rat unilateral carotid occlusion model we have shown both short and long term protection by hypothermia, but when the ...
BMJ (Clinical research ed.), 2014
BMJ, 2010
of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of tr... more of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of trials , 3 Malcolm Levene, professor of paediatrics and child health, 7,8 Brenda Strohm, trial coordinator, 3 Marianne Thoresen, professor of neonatal neuroscience, 9 Andrew Whitelaw, professor of neonatal medicine, 9 Denis Azzopardi, clinical reader in neonatal medicine 1,2 ABSTRACT Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.
Acta Paediatrica, 2007
Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and... more Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and neurological disability in the preterm infant. Proinflammatory cytokines have been implicated in the pathogenesis of white matter injury and subsequent cerebral palsy. The aim of this study was to determine the levels of proinflammatory cytokines in cerebrospinal fluid (CSF) from preterm infants with PHVD and to correlate the levels to white matter damage and neurodevelopmental outcome. CSF samples were obtained from 24 preterm infants with expanding PHVD and 19 preterm infants with normal ultrasound. Tumour necrosis factor-alphaa (TNF-alpha ), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) in CSF were measured by enzyme-linked immunosorbent assay, and IL-6 was measured by bioassay. The concentrations of TNF-alpha, IL-1beta, IL-6 and IL-8 were significantly elevated in CSF from infants with PHVD. TNF-alpha was detected in 43% of PHVD infants and 11% of controls (p = 0.04). IL-1beta was detected in 67% of PHVD infants and 0% of controls (p &lt; 0.0001). The concentrations of IL-6 were 368 (145-460) pg ml(-1) in the PHVD group and 30 (25-41) pg ml(-1) in the control group (p &lt; 0.0001), and those of IL-8 were 3000 (1620-3400) pg ml(-1) in the PHVD group and 35 (0-230) pg ml(-1) in the control group (p &lt; 0.0001). Cytokine concentrations did not correlate with white matter lesions on ultrasound, shunt dependence or neurological outcome within the PHVD group. There was an intense and prolonged inflammatory reaction in CSF from preterm infants with PHVD and a high risk for subsequent white matter injury and permanent neurological impairment.
PEDIATRICS, 2007
OBJECTIVE. Hydrocephalus is a serious complication of intraventricular hemorrhage in preterm infa... more OBJECTIVE. Hydrocephalus is a serious complication of intraventricular hemorrhage in preterm infants, with adverse consequences from permanent ventriculoperitoneal shunt dependence. The development of hydrocephalus takes several weeks, but no clinical intervention has been shown to reduce shunt surgery in such infants. The aim of this study was to test a new treatment intended to prevent hydrocephalus and shunt dependence after intraventricular hemorrhage.
Biology of the Neonate, 2003
Background: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic... more Background: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. Method: Thirtyeight newborn pigs were subjected to 45 min of global HI by ventilating them with F 6% O 2 . On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0°C for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35°C for 24 h before NT was resumed and the animals then survived a further 48 h. Results: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6
Pediatrics, 2000
Background. Clinical trials of mild cooling to 35°C or below in infants with early hypoxicischemi... more Background. Clinical trials of mild cooling to 35°C or below in infants with early hypoxicischemic encephalopathy are under way. The objective of this study was to systematically document cardiovascular changes associated with mild therapeutic hypothermia and rewarming in such infants.
Archives of Disease in Childhood-fetal and Neonatal Edition, 2000
Randomised clinical trials show that two injections of corticosteroid into the mother before pret... more Randomised clinical trials show that two injections of corticosteroid into the mother before preterm delivery reduce respiratory distress syndrome, neonatal mortality, and intraventricular haemorrhage. However, repeated courses of antenatal steroid are not backed by such evidence of safety and efficacy. Animal studies have shown that maternal corticosteroid delays myelination and reduces the growth of all fetal brain areas particularly the
PEDIATRICS, 2003
Objective. Treatment of posthemorrhagic ventricular dilation in premature infants is fraught with... more Objective. Treatment of posthemorrhagic ventricular dilation in premature infants is fraught with failures and complications. We have piloted a new treatment aimed at removing intraventricular blood and the cytokines associated with hydrocephalus.
Journal of Neurosurgery: Pediatrics, 2007
The combination of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PH... more The combination of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD) remains an important cause of disability in children surviving prematurity. Currently, there is no clear agreement on the management of neonatal IVH, apart from the eventual insertion of a shunt to control PHVD. Cerebrospinal fluid (CSF) shunts are associated with a relatively high complication rate in this population. The development of new treatment options requires greater understanding of the pathophysiological mechanisms of IVH and PHVD, as well as an opportunity to monitor closely their effects on the immature brain. The authors have developed a neonatal large animal model of IVH with long-term survival, allowing the full development of PHVD. Methods. Fourteen piglets that were 3 to 24 hours old were randomized to receive slow injections of autologous blood, autologous blood with elevated hematocrit, or artificial CSF after induction of general anesthesia. A fourth group served as controls. All animals underwent surgery to form an artificial fontanelle at the bregma. Physiological parameters, including intracranial pressure and electroencephalography, were monitored during injection. Results. Serial cranial ultrasonography studies performed during the 23-to 44-day survival period demonstrated progressive ventricular dilation in the animals injected with blood. Ventricular volumes, measured with image analysis software, confirmed the highest dilation after injection of blood with an elevated hematocrit. Histological evaluation showed fibrosis in the basal subarachnoid space of hydrocephalic piglets. Conclusions. This piglet model closely replicates human neonatal IVH and PHVD. It allows detailed physiological and ultrasonographic monitoring over a prolonged survival period. It is suitable for evaluation of noninvasive as well as surgical options in the management of IVH and PHVD.
Acta Paediatrica, 2008
Aim: Posthaemorrhagic ventricular dilatation (PHVD) after intraventricular haemorrhage (IVH) rema... more Aim: Posthaemorrhagic ventricular dilatation (PHVD) after intraventricular haemorrhage (IVH) remains a significant problem in preterm infants. No treatment has reduced the need for cerebrospinal fluid (CSF) diversion. Considerable evidence implicates transforming growth factor-β (TGF-β) in the pathogenesis of PHVD. Pirfenidone and losartan reduce TGF-β expression and decrease postinflammatory fibrosis in the lungs, kidneys, heart and liver. They have excellent CSF and brain penetration. We hypothesized that administration of pirfenidone or losartan would reduce ventricular dilatation. Methods: Ninety-two rat pups underwent intraventricular blood injection on postnatal days (PN) 7 and 8, and were randomised to pirfenidone, losartan or water by gavage for 14 days. Neuromotor testing was carried out twice weekly. After sacrifice at PN21, ventricular area was measured on coronal sections using image-analysis software.
The Journal of Emergency Medicine, 2014
Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in mid... more Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.)
Journal of Microbiological Methods, 2015
Streptococcus agalactiae (GBS) is a leading cause of invasive neonatal infection. Serotyping of G... more Streptococcus agalactiae (GBS) is a leading cause of invasive neonatal infection. Serotyping of GBS is important in following epidemiological trends and vaccine development. Capsular serotyping of GBS by latex agglutination has been the predominant typing method, but more recently capsular genotyping has been introduced as an alternative method. The purpose of this study was to compare the relative performance of these methods in a contemporary population of pregnant women. We typed isolates from an unselected population of 426 colonized women at delivery using latex agglutination and a combination of four PCR methods. Antibiotic resistance was tested in 449 isolates. Capsular genotyping gave a result in all except three of 426 isolates. Fifty-nine of 426 isolates could not be typed by latex agglutination. Agreement between serotyping and genotyping was shown in 303 (71.1%) of the isolates. 10.2% of the isolates were resistant to erythromycin, 9.6% to clindamycin, 76.6% to tetracycline and none to penicillin. In conclusion, a substantial proportion of the colonizing strains were non-typeable by serotyping, but typeable by genotyping. This suggests that a diagnostic genotyping strategy is preferable to serotyping of the GBS polysaccharide capsule in colonized, pregnant women.
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Papers by Andrew Whitelaw