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Objective: Therapeutic hypothermia (HT) is the standard treatment for newborns after perinatal asphyxia. Preclinical studies report that HT is more effective when started early. Methods: Eighty cooled newborns were analyzed and grouped according to when cooling was started after birth: early (≤180 min) or late (>181 min). For survivors we analyzed whether starting cooling early was associated with a better psychomotor or mental developmental index (PDI or MDI, Bayley Scales of Infant Development II) than late cooling. Results: Forty-three newborns started cooling early and 37 started late. There was no significant difference in the severity markers of perinatal asphyxia between the groups; however, nonsurvivors (n = 15) suffered more severe asphyxia and had significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that survived, 35 were cooled early and 30 were cooled late. There was no difference in time to start cooling between those who survived and those who did not. For survivors, median PDI (IQR) was significantly higher when cooled early [90 (77-99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no increase in cardiovascular adverse effects in those cooled early. There was no significant difference in MDI between early and late cooling [93 (77-103) vs. 89 (76-106), p = 0.594]. Conclusion: Starting cooling before 3 h of age in surviving asphyxiated newborns is safe and significantly improves motor outcome. Cooling should be initiated as soon as possible after birth in eligible infants.

Improving neurodevelopmental outcome for preterm infants is an important challenge for neonatal medicine. The disruption of normal brain growth and neurological development is a significant consequence of preterm birth and can result in physical and cognitive impairments. While advances in neonatal medicine have led to progressively better survival rates for preterm infants, there has only been a modest improvement in the proportion of surviving infants without neurological impairment, and no change in the proportion with severe disability. The overall number of children with neurodisability due to prematurity is increasing. Trials investigating novel therapies are underway and many have promising early results; however, in the interim, current treatments and management strategies that have proven benefit for neurodevelopment or reduction in neonatal brain injury are often underutilised. We collate the evidence for the efficacy of such interventions, recommended by guidelines or supported by large metaanalysis or randomised control trials. We address controversies that have hindered uptake and problems with translating research into practice. We then look to the future of preterm neuroprotective care.

Background The parameters of the optic disc and peripapillary retinal nerve fibre layer (pRNFL) in premature children may vary with disease processes that contribute to visual impairment and blindness and so could be useful as an objective measure in at-risk children. Methods A systematic review of current literature on the range of pRNFL and optic disc parameters in children aged less than 18 years, who were born before 37 weeks gestation, will be performed. The bibliographic databases MEDLINE, CINAHL, EMBASE, Scopus and Web of Science will be systematically searched. Where possible and appropriate, study-specific estimates will be combined using meta-analysis to obtain an overall summary estimate of pRNFL thickness and cup-disc ratio across studies, and results will be presented by age of population. Discussion This review aims to improve understanding of what might be considered within/outside the range of normality for this high-risk group. Systematic review registration The review is registered on PROSPERO: CRD42016037933 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0319-0) contains supplementary material, which is available to authorized users.

GABA(B) receptors (GABA(B)Rs) are involved in early events during neuronal development. The presence of GABA(B)Rs in developing oligodendrocytes has not been established. Using immunofluorescent co-localization, we have identified GABA(B)R proteins in O4 marker-positive oligodendrocyte precursor cells (OPCs) in 4-day-old mouse brain periventricular white matter. In culture, OPCs, differentiated oligodendrocytes (DOs) and type 2 astrocytes (ASTs) express both the GABA(B1abcdf) and GABA(B2) subunits of the GABA(B)R. Using semiquantitative PCR analysis with GABA(B)R isoform-selective primers we found that the expression level of GABA(B1abd) was substantially higher in OPCs or ASTs than in DOs. In contrast, the GABA(B2) isoform showed a similar level of expression in OPCs and DOs, and a significantly higher level in ASTs. This indicates that the expression of GABA(B1) and GABA(B2) subunits are under independent control during oligodendroglial development. Activation of GABA(B)Rs using the selective agonist baclofen demonstrated that these receptors are functionally active and negatively coupled to adenylyl cyclase. Manipulation of GABA(B)R activity had no effect on OPC migration in a conventional agarose drop assay, whereas baclofen significantly increased OPC migration in a more sensitive transwell microchamber-based assay. Exposure of cultured OPCs to baclofen increased their proliferation, providing evidence for a functional role of GABA(B)Rs in oligodendrocyte development. The presence of GABA(B)Rs in developing oligodendrocytes provides a new mechanism for neuronal-glial interactions during development and may offer a novel target for promoting remyelination following white matter injury.

Objective: To evaluate the relationship between superior vena cava flow (SVCF) measurements within the first 24 h of life, and development of intraventricular haemorrhage (IVH) in extremely preterm infants.Study design: Single centre retrospective cohort study of 108 preterm infants born less than 28 weeks’ gestation. Main outcome measure was degree of IVH at day 7 postnatal age.Results: The mean GA of the study group was 25.4 weeks. Mean SVCF was lower (75 ml/kg/min) in infants later diagnosed with IVH (n = 46) compared to infants, who did not develop IVH (87.7 ml/kg/min, p = 0.055). PDA diameter was inversely associated with SVCF (p = 0.024) and reversal of flow in the descending aorta (p = 0.001). Sensitivity analysis did not confirm an independent association of SVCF with development of IVH [OR 0.990 (0.978–1.002), p = 0.115].Conclusion: Our study describes early SVCF in extremely preterm infants is associated with the extent of ductal shunting, but insensitive in predicting IVH.

Oligodendrocytes (OLs) are responsible for axon myelination and are the principal cells targeted in preterm white matter injury. The cellular and molecular mechanisms involved in white matter development and immature OL injury are incompletely understood. Metabotropic glutamate receptors (mGluRs) modulate neuronal development and survival, and have recently been identified in oligodendrocyte progenitor cells (OPCs). Using the highly homogeneous CG-4 OPC line and O4 marker-immunoselected primary OLs, we established the differentiation stage-specific expression profile of mGluR3 and mGluR5 mRNAs and proteins in the oligodendroglial lineage and type-2-astrocytes (ASTs). Our quantitative analysis indicated no changes in mGluR3, but a significant down-regulation of mGluR5a mRNA and protein expression during differentiation of OPCs into OLs or ASTs. The down-regulation of mGluR5a had functional consequences, with significantly fewer OLs and ASTs than OPCs responding to the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine with intracellular Ca(2+) concentration oscillations. Neither stimulation nor inhibition of mGluR3 or mGluR5 altered OPC migration, suggesting that these receptors do not play prominent roles in the regulation of OPC motility. The activation of mGluR5 completely protected OPCs and substantially reduced staurosporine-induced apoptosis in OLs. This suggests that the down-regulation of mGluR5 in premyelinating OLs is likely to contribute to their increased vulnerability, and that the targeting of mGluR5 may be a potential therapeutic strategy for future development.

To compare differences in the management of the neonatal patent ductus arteriosus between neonatologists and paediatric cardiologists, physicians throughout the South-West were contacted. In treatment-refractory cases, neonatologists considered ligation less frequently than paediatric cardiologists (0% versus 40%; p

To compare the overall performance of specially trained neonatal nurses acting autonomously, unsupervised, and without a protocol with specialist registrars when weaning neonates from mechanical ventilation.Prospective, randomized, controlled trial.A single neonatal intensive care unit.Neonates requiring conventional mechanical ventilation (n = 50).Infants on conventional ventilation were randomly assigned to receive either nurse-led (n = 25) or registrar-led (n = 23) weaning. A total of 48 infants completed the study (two infants in the registrar group were excluded when their parents withdrew consent).The main outcome measure, median weaning time, was 1200 mins (95% confidence interval [CI], 621-1779 mins) in the nurse group and 3015 mins (95% CI, 2650-3380 mins) in the registrar group (p = .0458). The median time from treatment assignment to the first ventilator change was 60 mins (95% CI, 52-68 mins) in the nurse group and 120 mins (95% CI, 103-137 mins) in the registrar group (p = .35). On average, the nurses made ventilator changes every 4.5 hrs (95% CI, 2.9-6 hrs) and the registrars every 7.2 hrs (95% CI, 5.4-9 hrs; p = .003). The median number (range) of backward steps taken per infant was 0 (0-5 steps) in the nurse group and 1 (0-5 steps) in the registrar group (p = .019).The findings of this study suggest that additional domains of neonatal critical care could be reviewed for their potential transfer to appropriately prepared nurses.

Background: Single-strand conformational polymorphism (SSCP) is still a frequently used genotyping method across different fields for the detection of single nucleotide polymorphisms (SNPs) due to its simplicity, requirement for basic equipment accessible in most laboratories and low cost. This technique was previously used to detect rs4354668:A > C (g.-181A > C) SNP in the promoter of astroglial glutamate transporter (EAAT2) and the same approach was initially used here to investigate this promoter region in a cohort of newborns.Results: Unexpectedly, four distinct DNA migration patterns were identified by SSCP. Sanger sequencing revealed two additional SNPs: g.-200C > A and g.-168C > T giving a rise to a total of ten EAAT2 promoter variants. SSCP failed to distinguish these variants reliably and thus pyrosequencing assays were developed. g.-168C > T was found in heterozygous form in one infant only with minor allele frequency (MAF) of 0.0023. In contrast, g.-200C > A and -181A > C were more common (with MAF of 0.46 and 0.49, respectively) and showed string evidence of linkage disequilibrium (LD). In a systematic comparison, 16% of samples were miss-classified by SSCP with 25-31% errors in the identification of the wild-type and homozygote mutant genotypes compared to pyrosequencing or Sanger sequencing. In contrast, SSCP and pyrosequencing of an unrelated single SNP (rs1835740:C > T), showed 94% concordance.Conclusion: Our data suggest that SSCP cannot always detect reliably several closely located SNPs. Furthermore, caution is needed in the interpretation of the association studies linking only one of the co-inherited SNPs in the EAAT2 promoter to human diseases. © 2014 Rajatileka et al.; licensee BioMed Central Ltd.

The treatment of pulmonary hypertension (PH) secondary to bronchopulmonary dysplasia (BPD) in infants has evolved in recent years, improving both quality of life and survival for patients. One of the potential agents for this condition is sildenafil, a phosphodiesterase-V inhibitor with proven efficacy within the idiopathic PH population. However, only limited evidence exists for its use as either monotherapy or part of a combination approach towards the management of PH in BPD. This review summarises the evidence base for sildenafil alone and in combination with other recognised therapeutic agents for ameliorating paediatric PH in the presence of BPD. It also examines the suitability for current practice with the aim of clarifying regimens that produce improved patient outcomes. We conclude that sildenafil is both safe and effective in this utility. Doses should be started at 0.5 mg/kg every 8 h before titrating up towards 2 mg/kg every 6 h to effect reductions in pulmonary vascular resistance and arterial pressure. Evidence suggests that if continued until PH resolution, this improves survival from 61% to 81% at 12 months. Furthermore, there are also data suggesting that in treatment refractory PH cases, the addition of endothelin antagonists and prostacyclin analogues to sildenafil therapy can also be considered.

Glial precursor cells (GPCs) are present in the adult human central nervous system (CNS) and they can be isolated and maintained in culture for in vitro studies. This study analysed expression of mGluR3 and mGluR5 metabotropic glutamate receptor (mGluR) mRNAs in GPCs. A2B5 surface antigen positive GPCs were isolated using immunomagnetic selection from dissociated temporal lobe subcortical white matter cells. The separated GPCs were maintained in cultures and characterised by immunoreactivity for the differentiation markers A2B5 and human platelet-derived growth factor-alpha receptor (PDGFalphaR). Reverse transcription followed by multiplex PCR analysis showed that the GPCs expressed both mGluR3 and mGluR5a mRNAs. Double immunostaining for glial progenitor markers and mGluR5 proteins demonstrated that all A2B5 and PDGFalphaR-positive cells were also positive for mGluR5. The results indicate that GPCs present in the adult human CNS express mGluR3 and mGluR5a. These neurotransmitter receptors may be involved in the proliferation and differentiation of glial cells.

We investigated the expression of metabotropic glutamate receptor (mGluR) isoforms in CG-4 rodent oligodendroglial progenitor cells (OPC) and rat brain oligodendrocytes. Our RT-PCR analysis detected mRNAs for mGluR3 and mGluR5 isoforms in OPCs. Although neurons express both mGluR5a and mGluR5b splice variants, only mGluR5a was identified in OPCs. Antibodies to mGluR2/3 and mGluR5 detected the corresponding receptor proteins in immunoblots of OPC membrane fractions. Furthermore, immunocytochemical analysis identified mGluR5 in oligodendrocyte marker O4-positive OPCs. The expression of mGluR5 was also demonstrated in oligodendrocyte marker (O4 and O1) positive cells in white matter of postnatal 4- and 7-day-old rat brain sections using immunofluorescent double labelling and confocal microscopy. The mGluR5 receptor function was assessed in CG-4 OPCs with fura-2 microfluorometry. Application of the mGluR1/5 specific agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induced calcium oscillations, which were inhibited by the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). The DHPG induced calcium oscillations required Ca2+ release from intracellular stores. In OPCs the group II mGluR agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) decreased forskolin-stimulated cAMP synthesis, indicating the presence of functional mGluR3. The newly identified mGluR3 and mGluR5a may be involved in the differentiation of oligodendrocytes, myelination and the development of white matter damage.

Background Very low birth weight (VLBW) infants with late onset sepsis have increased risk of neurodisability. Care bundles to reduce these infections in NICU are effective. The impact of care bundles on long-term neurodevelopmental outcome has not been described. We aimed to determine if implementation of a sepsis-reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A multimodal sepsis improvement bundle was implemented in a regional NICU from July 2006. This bundle focused on hand hygiene and line care improvements. Mortality and neurological morbidity rates were compared pre- and post intervention (Jan ‘01 - Dec ‘07 vs. Jul ‘08 – Dec ‘12). Infants had neurodevelopmental assessment at 24 months corrected gestation with Bayley Scales of Infant development. Moderate cognitive disability was defined as a cognitive/language score below 2SDs, moderate motor disability as a motor score below 2SDs. Results Birth weight, gestation and gender were similar in both cohorts. Coagulase Negative Staphylococcus septicaemia rates reduced from 7/1000 care days before implementation to 2.8/1000 in 2012. Mortality rates were similar between the groups (66/426 vs. 40/310; p = 0.3). There was no difference in moderate motor disability (17/85 vs. 3/42; p = 0.07). There was a significant reduction in moderate cognitive disability (16/86 vs. 2/44; p = 0.03) after implementation of the sepsis care bundle. Conclusions Sepsis-reduction care bundles improve the 2-year neurodevelopmental outcome of VLBW infants. The improvement seen in cognitive function is likely to translate into significantly less long-term learning disability.

Reducing adverse neurodevelopmental outcomes associated with preterm birth is a major challenge facing neonatal medicine, as abnormalities engendered during the perinatal period have lifelong implications. The pathological mechanisms leading to abnormal neurodevelopment in preterm infants involve several pathways. Many direct and indirect effects of preterm birth on neural development occur at the micro structural or neurochemical level, meaning that current methods for assessing neurological injury in preterm infants provide only limited mechanistic and prognostic information. A promising alternative approach is the use of resting state functional MRI (rs-fMRI) to infer integration of neural activity across brain regions (functional connectivity (FC)). Adults who were born preterm show persistent differences in FC, and early detection of such changes offers potential insights into the pathophysiology of preterm brain injury. These functional changes may be influenced by both neonatal course and underlying susceptibilities to abnormal development, including genetic factors. We utilised rapid multiband sequence rs-fMRI acquisition at 3 Tesla, to characterise functional brain connectivity in 30 infants born at

Background Very low birth weight infants (VLBW; Objective To determine if the implementation of a sepsis reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A sepsis improvement care bundle was implemented in a tertiary level NICU between 2006–2007. Mortality and neurological morbidity rates were compared for the pre-intervention (January 2001–December 2007) and post-intervention (July 2008–December 2012) periods. The highest risk VLBW infants ( Results Coagulase Negative Staphylococcus septicaemia rates were 7/1000 care days before implementation of the care bundle and have reduced to an average of 2.8/1000 care days by 2013. In the cohort of VLBW infants there was no significant reduction in mortality rates (66/426(16%) vs. 40/310(13%); p = 0.3). A significant reduction in moderate cognitive disability (16/86(19%) vs. 2/44(5%); p = 0.03) was found after full implementation of the sepsis care bundle. Potentially confounding variables (birth weight and gender) were not different (p > 0.05) in the pre and post intervention cohorts. Conclusions This is the first description of the long term impact of a sepsis improvement care bundle on neurodevelopmental outcomes in VLBW infants. The improvement seen in cognitive function at 2 years is likely to translate into significantly less long term learning disability.

Preterm birth is associated with adverse neurodevelopmental outcomes. The pathological mechanisms leading to adverse outcomes involve several pathways, which are not fully understood. Current methods of assessing neurological injury associated with preterm birth have limited scope and low prognostic value. Whilst structural MRI may provide detailed anatomical information about the neonatal brain, there is imperfect mapping between structure and function. A supplementary approach is the use of functional MRI (fMRI) to infer functional connectivity (FC), evaluating integration of neural activity within the brain. There is emerging evidence that children who were born preterm show long term changes in FC, and early detection of such changes offers potential to improve understanding of pathophysiology of preterm brain injury. These functional changes may be influenced by both neonatal course and underlying susceptibilities to abnormal development, including genetic risk factors. We used resting state fMRI (rs-fMRI) at 3T to examine functional brain connectivity in 20 infants born at

Understanding how the immature brain develops functional networks is a key challenge in neonatology. Analysis of functional MRI (fMRI) images acquired ‘at rest’ (rs-fMRI) allows inference of coordinated neural activity across disparate brain regions (functional connectivity (FC)). There is increasing interest in exploring neonatal brain development using rs-fMRI. Most rs-fMRI work has focussed on fluctuations in blood oxygenation level dependent (BOLD) fMRI signals occurring at A method of improving rs-fMRI sampling frequency is ‘multiband’ parallel EPI, where multiple brain slices are excited simultaneously and spatially distributed receiver coils are used to encode anatomical data, allowing accelerated data reconstruction. We employed a rapid (TR = 906 ms) multiband rs-fMRI protocol to examine FC in 20 ex-preterm infants, probing BOLD fluctuations up to 0.5 Hz. We present power spectra, SNR data and comparisons of FC data at different frequencies, identifying unique functional changes at frequencies >0.2 Hz, which are not effectively identified within lower frequency fluctuations. This is the first description of multiband fMRI in neonates, and we discuss the implications for understanding infant brain networks.

Background Published data suggest that very low birth weight infants (VLBW; Objective To determine if the implementation of a sepsis reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A sepsis improvement care bundle, based on the Vermont Oxford Network iNIQ package, was implemented in stages in a tertiary level NICU between 2006 and 2007. Mortality and neurological morbidity rates were compared for the pre-intervention (January 2001 to December 2007) and post-intervention (July 2008 to December 2012) periods. We excluded the 6 month period directly following full implementation of the intervention. The highest risk VLBW infants ( Results Coagulase Negative Staphylococcus septicaemia rates were 7/1000 care days before implementation of the care bundle and from 2009, have reduced year on year to an average of 2.8/1000 care days by 2013. In the cohort of VLBW infants there was no significant reduction in mortality rates (66/426(16%) vs. 40/310(13%); p = 0.3). No significant difference was found in moderate motor disability (17/85(20%) vs. 3/42(7%); p = 0.07) or CP (10/94(11%) vs. 6/49(12%); p = 0.7), before and after the intervention. A significant reduction in moderate cognitive disability (16/86(19%) vs. 2/44(5%); p = 0.03) was found after full implementation of the sepsis care bundle. Potentially confounding variables (birth weight and gender) were not different (p > 0.05) in the pre and post intervention cohorts. Conclusions This is the first description of the long term impact of a sepsis improvement care bundle on neurodevelopmental outcomes in VLBW infants. The improvement seen in cognitive function at two years of age is likely to translate into significantly less long term learning disability.

AIM—To determine whether patient triggered ventilation (PTV) leads to greater exposure to significant hypocarbia than conventional ventilation (CMV) in premature infants during the first 72 hours of life. METHODS—Infants of 32 weeks gestation or less were included. Randomisation yielded 74 infants on PTV and 68 infants on CMV. Arterial PaCO2 measurements were taken four hourly for the first 72 hours of life. RESULTS—The mean PaCO2 levels on days 1, 2, and 3 were not significantly different between the two groups. The proportion of infants with PaCO2 levels of 3.33 kPa or less did not differ between PTV and CMV infants. Mean percentages of infants with this level of hypocarbia at any time were 31.4%, 18.9%, 8.8% on days 1, 2, and 3 respectively. Cumulative hypocarbia, below a 3.33 kPa threshold, was 0.0084 kPa.h (PTV) versus 0.0263 kPa.h (CMV) per hour ventilated during the first 24 hours (p = 0.259). Risk factors associated with hypocarbia on day 1 were peak inspiratory pressure below 14 cm H2O (odds ratio 4.79) as well as FiO2 below 0.30 (odds ratio 3.42). CONCLUSION—Exposure to hypocarbia (PaCO2 3.33 kPa or below) was not significantly different between PTV and CMV infants during the first 72 hours of life. Hypocarbia was common in both groups on day 1 and to a lesser extent on day 2. Infants with the least requirements for ventilatory support were at highest risk of hypocarbia on day 1 of life. Preterm infants with mild hyaline membrane disease require a more aggressive approach to weaning on both modes of ventilation, followed by extubation to limit the risk of hypocarbia.

Aim To determine the etiological association, neurodevelopmental sequelae and role of Magnetic Resonance Imaging (MRI) in term newborn infants with seizures. Methods Cohort study of infants >37 weeks gestation delivered in a single level 3 centre in the UK from 1/12/2004 to 31/10/2009 (59 months), prospectively identified by a perinatal morbidity surveillance system and followed longitudinally for 18–24 months. Results 77 infants were identified with seizures during the study period (3.0/1000 live births). 9 infants died (12%). 73/77 (95%) had an aEEG recording and 70/77 (91%) had an MRI scan. In 95% of cases an underlying cause of seizures was elucidated. The most common diagnosis was HIE (65%) with neonatal stroke as the second most common diagnosis (12%). Overall, 28/77 (36%) of the cohort had a neurodevelopmental impairment (NDI), ranging from mild to severe. 37/50 infants with HIE (74%) received therapeutic hypothermia and 9 (24%) had NDI. Of the remaining 13 managed with normothermia, 4 had NDI (31%). NDI was prevalent in those with a diagnosis other than HIE (15/27; 56%), in particular stroke, hypoglycaemia and cerebral dysgenesis. 15/77 (19%) had recurrence of seizure in the first 2 years of life. The highest risk of seizure recurrence was in cerebral dysgenesis, hypoglycaemia and stroke. Infants with HIE had a very low risk of seizure recurrence (1/50; 2%). 45/70 (64%) had abnormal MRI findings. The negative predictive value of a normal MRI in survivors of developing any disability was 0.93. Conclusion This is the first report of a cohort of term infants with seizures fully investigated by MRI and aEEG. HIE was the most common cause of seizures in this population. Neonatal stroke was the most likely diagnosis for term infants presenting with seizures on day two of life. The universal use of MRI allows a cause to be identified in 95% of term infants with seizures. A normal MRI scan was highly predictive of a normal neurodevelopmental outcome. There was significant risk of NDI and seizure recurrence, particularly in those with a diagnosis other than HIE, supporting formal neurological surveillance.

Aim To compare the differences in the management of the patent ductus arteriosus (PDA) between neonatologists and paediatric cardiologists in the context of the current evidence base. Method Consultant and registrar neonatologists and paediatric cardiologists throughout the deanery were contacted via email to complete an online cross-sectional survey collecting quantitative and qualitative data on the management of a neonatal PDA. The survey included 26 points and was largely scenario based. The questionnaire was validated through an initial local pilot. No ethical approval was required. Results Of the 53 physicians contacted, 20 neonatologists and 26 paediatric cardiologists completed the questionnaire (87% response rate). Paediatric cardiologists are significantly more likely than neonatologists (60% vs 31%; p Conclusion For the first time we have shown that the practises of paediatric cardiologists vary significantly from those of neonatologist when managing a PDA. These differences may reflect a lack of consistent data regarding PDA closure and highlight the need for greater guidance in this controversial area. We have shown such guidance to be in strong demand by physicians. Moreover, such work could facilitate a practise that better reflects the current best-evidence.

Aims Bilious vomiting in the newborn is a potentially life threatening emergency. Malrotation, a disorder of abnormal intestinal rotation and fixation, predisposes newborns to midgut volvulus. Plain abdominal films and upper gastrointestinal contrast studies form the mainstay of radiological diagnosis. 1) To determine the incidence of surgical pathology in newborns with bilious vomiting referred to a regional paediatric surgical centre. 2) To assess the predictive value of radiological investigations Methods A total of one hundred and fourteen infants referred for radiological assessment on the day of presentation were identified from the regional radiological database (October 2006–April 2008). Exclusion criteria included abdominal wall defects, congenital cardiac conditions, congenital anomalies and vomiting beyond the neonatal period. A total of 23 infants were excluded. All infants had plain abdominal films and upper gastrointestinal contrast studies. In addition, five infants had abdominal ultrasonography. Results 18.6% (17/91) of newborns presented with intestinal pathology, of which all 17 required surgery. Thirteen newborns (14.2%) had malrotation (seven had additional midgut volvulus), two had a duodenal web, one each had colonic pneumatosis and intussusception. Plain films and clinical examination did not suggest malrotation in the positive cases. Upper gastrointestinal contrast studies diagnosed malrotation in eleven cases, equivocal diagnosis of malrotation in two cases with midline duodenojejunal junction and a diagnosis of duodenal web in a further two cases. The predictive value of upper gastrointestinal contrast studies in diagnosing malrotation was 85%. Ultrasonography secured the diagnosis of midgut volvulus based on the “whirlpool sign”, in the two equivocal cases with midline duodenojejunal junction and this was confirmed during surgery. All thirteen cases had a Ladd9s procedure. None had ischaemic bowel. Conclusion The incidence of malrotation in our population is less than previously reported, probably because our regional policy dictates that all infants with a single bilious vomit require specialist investigation. This study confirms that clinical examination and plain abdominal films have no predictive value in diagnosing midgut volvulus. The study also confirmed that upper gastrointestinal contrast studies, in combination with ultrasound improves the predictive value in diagnosing surgical pathology.

St Michael9s NICU (StMH) provides pre and postoperative care for all newborns with an ante/postnatal diagnosis of congenital diaphragmatic hernia (CDH) in South-West England. A consistent care bundle is followed for antenatal diagnoses: delivery at StMH, sedation and muscle relaxation at birth, elective intubation, high frequency oscillatory ventilation (HFOV), inotropic support, pulmonary vasodilators and delayed surgery. ECMO is only considered for reversible pulmonary hypertension when conventional management fails. Objectives To review clinical management and evaluate survival/morbidity in infants with CDH over a 12 year period. Methods A retrospective case note review of all CDH cases managed at StMH(1998–2010). A review of the South-West Congenital Anomaly Register. Results 79 cases were identified, including 45 identified antenatally. 16 (20%) had additional major malformations/genetic syndromes; 2 lethal. Overall survival was 60/79(76%). The anomaly register identified 4 additional CDH deaths in local hospitals for this population. 100% of infants delivered at StMH received the full care bundle (91% received HFOV). No cases received ECMO. 10/79(12.6%) had pneumothoraces. 13/60(21%) of survivors required additional oxygen at 28 days of life and 3/60(5%) were discharged on oxygen. Domiciliary oxygen was not required for any infant delivered at StMH (where the complete care bundle was followed). Conclusion Our survival rate compares favourably with recent large published series and is not significantly biased by ‘hidden mortality’ in the South-West Region. Pneumothorax and chronic lung disease rates are significantly lower than recently published studies using HFOV. Our consistent approach delivers favourable survival rates with a low pulmonary morbidity burden in survivors.

Background Genotyping requires biological sample collection that must be reliable, convenient and acceptable for patients and clinicians. Finding the most optimal procedure of sample collection for premature neonates who have a very limited blood volume is a particular challenge. The aim of the current study was to evaluate the use of umbilical cord (UC) tissue and newborn dried blood spot (DBS)-extracted genomic DNA (gDNA) as an alternative to venous blood-derived gDNA from premature neonates for molecular genetic analysis. All samples were obtained from premature newborn infants between 24-32 weeks of gestation. Paired blood and UC samples were collected from 31 study participants. gDNA was extracted from ethylenediaminetetraacetic acid (EDTA) anticoagulant-treated blood samples (~500 μl) and newborn DBSs (n = 723) using QIAamp DNA Micro kit (Qiagen Ltd., Crawley, UK); and from UC using Qiagen DNAeasy Blood and Tissue kit (Qiagen Ltd., Crawley, UK). gDNA was quantified and purity confirmed by measuring the A260:A280 ratio. PCR amplification and pyrosequencing was carried out to determine suitability of the gDNA for molecular genetic analysis. Minor allele frequency of two unrelated single nucleotide polymorphisms (SNPs) was calculated using the entire cohort. Results Both whole blood samples and UC tissue provided good quality and yield of gDNA, which was considerably less from newborn DBS. The gDNA purity was also reduced after 3 years of storage of the newborn DBS. PCR amplification of three unrelated genes resulted in clear products in all whole blood and UC samples and 86%-100% of newborn DBS. Genotyping using pyrosequencing showed 100% concordance in the paired UC and whole blood samples. Minor allele frequencies of the two SNPs indicated that no maternal gDNA contamination occurred in the genotyping of the UC samples. Conclusions gDNAs from all three sources are suitable for standard PCR and pyrosequencing assays. Given that UC provide good quality and quantity gDNA with 100% concordance in the genetic analysis with whole blood, it can replace blood sampling from premature infants. This is likely to reduce the stress and potential side effects associated with invasive sample collection and thus, greatly facilitate participant recruitment for genetic studies.