Major inclusion and exclusion criteria of studies included in the meta-analysis.

<p>Major inclusion and exclusion criteria of studies included in the meta-analysis.</p

Quality of included studies.

<p>Quality of included studies.</p

Funnel plot of the included studies.

<p>Funnel plot of the included studies.</p

Characteristics of excluded studies.

<p>ND, not described; NE, neonatal encephalopathy.</p

Additional file 1: of Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: an example of a neonatal cooling trial

CONSORT 2010 checklist. (PDF 677 kb

Effect of cooling on neonatal sepsis.

<p>Effect of cooling on neonatal sepsis.</p

Effect of cooling on neonatal mortality.

<p>Effect of cooling on neonatal mortality.</p

Characteristics of the in-trial population of studies included in the meta-analysis.

<p>All data are mean (SD) unless specified otherwise</p><p>HYPO, Hypothermic arm; STD, Standard care arm; NA, not available; NE, neonatal encephalopathy.</p>*<p>Original number recruited into cooled and standard care arms. Nineteen infants in the cooled arm were then excluded and a further 19 lost to follow up. Two infants in the standard care arm were subsequently excluded and a further 22 lost to follow up. Thus the authors reported outcome data on 100 and 94 standard care infants.</p

Transcriptomics of Maternal and Fetal Membranes Can Discriminate between Gestational-Age Matched Preterm Neonates with and without Cognitive Impairment Diagnosed at 18–24 Months

<div><p>Background</p><p>Neurocognitive impairment among children born preterm may arise from complex interactions between genes and the intra-uterine environment.</p><p>Objectives</p><p>(<b>1</b>) To characterize the transcriptomic profiles of chorioamniotic membranes in preterm neonates with and without neurocognitive impairment via microarrays and (<b>2</b>) to determine if neonates with neurocognitive impairment can be identified at birth.</p><p>Materials/Methods</p><p>A retrospective case-control study was conducted to examine the chorioamniotic transcriptome of gestational-age matched very preterm neonates with and without neurocognitive impairment at 18–24 months’ corrected-age defined by a Bayley-III Cognitive Composite Score <80 (n = 14 each). Pathway analysis with down-weighting of overlapping genes (<b>PADOG</b>) was performed to identify KEGG pathways relevant to the phenotype. Select differentially expressed genes were profiled using qRT-PCR and a multi-gene disease prediction model was developed using linear discriminant analysis. The model’s predictive performance was tested on a new set of cases and controls (n = 19 each).</p><p>Results</p><p><b>1</b>) 117 genes were differentially expressed among neonates with and without subsequent neurocognitive impairment (p<0.05 and fold change >1.5); <b>2</b>) Gene ontology analysis indicated enrichment of 19 biological processes and 3 molecular functions; <b>3</b>)<b>PADOG</b> identified 4 significantly perturbed KEGG pathways: oxidative phosphorylation, Parkinson’s disease, Alzheimer’s disease and Huntington’s disease (q-value <0.1); <b>4</b>) 48 of 90 selected differentially expressed genes were confirmed by qRT-PCR, including genes implicated in energy metabolism, neuronal signaling, vascular permeability and response to injury (e.g., up-regulation of <i>SEPP1</i>, <i>APOE</i>, <i>DAB2</i>, <i>CD163</i>, <i>CXCL12</i>, <i>VWF;</i> down-regulation of <i>HAND1</i>, <i>OSR1</i>)(p<0.05); and <b>5</b>) a multi-gene model predicted 18–24 month neurocognitive impairment (using the ratios of <i>OSR1/VWF</i> and <i>HAND1/VWF</i> at birth) in a larger, independent set (sensitivity = 74%, at specificity = 83%).</p><p>Conclusions</p><p>Gene expression patterns in the chorioamniotic membranes link neurocognitive impairment in preterm infants to neurodegenerative disease pathways and might be used to predict neurocognitive impairment. Further prospective studies are needed.</p></div

Baseline neonatal characteristics of the two study groups.

<p>CRIB II score- clinical risk index for babies score;</p><p>*P-value is significant at alpha < 0.05 level of significance</p><p>For all samples used in the microarray and qRT-PCR experiments, the 28S/18S ratios for RNA ranged from 1.7 to 2.0 and RNA integrity numbers ranged from 7.5 to 9.6.</p><p>Baseline neonatal characteristics of the two study groups.</p