Socio-ecological determinants of lifestyle behavior of women with overweight or obesity before, during and after pregnancy: qualitative interview analysis in the Netherlands.

BACKGROUND: Maternal overweight and obesity are related to several health risks in the periods before, during and after pregnancy including a higher risk of gestational diabetes mellitus, preeclampsia and preterm birth. At the same time, women's daily life quickly changes in these periods. Therefore, we hypothesize that the value of determinants of lifestyle behavior within different levels of the socio-ecological model differ accordingly and influence lifestyle behavior. These dynamics of determinants of lifestyle behavior in the periods before, during and after pregnancy are unexplored and therefore evaluated in this study. These insights are needed to offer appropriate guidance to improve lifestyle in women of childbearing age. METHODS: Individual semi-structured interviews were conducted before, during or after pregnancy in 26 women with overweight or obesity living in the Netherlands. Questions covered all levels of the socio-ecological model, i.e. intrapersonal, interpersonal, institutional and environmental/societal. All interviews were transcribed and coded. RESULTS: Determinants at all levels of the socio-ecological model were perceived as relevant by women of childbearing age. Various determinants were mentioned including knowledge of a healthy lifestyle, social support, access to customized lifestyle guidance, and distance to healthy lifestyle supporting activities. The importance women attributed to determinants differed between the periods before, during and after pregnancy. Before pregnancy, child's wellbeing as motivator for adopting a healthy lifestyle was mentioned less frequently than during and after pregnancy. Women described that the interplay and balance between determinants varied on a daily basis, and not merely per period. This was often expressed as fluctuation in energy level per day which influences their willingness to put effort in making healthy choices. CONCLUSIONS: Findings of this study confirm the importance of determinants at multiple socio-ecological levels for shaping lifestyle behavior in women of childbearing age. The findings add to current insights that the perceived importance of determinants and their interplay differ before, during and after pregnancy. They influence lifestyle behavior decisions, not only per period but even on a daily basis, in particular in this phase of life. This perspective can be helpful in optimizing lifestyle guidance for women of childbearing age in order to prevent perinatal complications.

Prediction of asthma exacerbations in children: results of a one-year prospective study.

BACKGROUND: Underdiagnosis and low levels of asthma control are frequent occurring problems in patients with asthma. OBJECTIVE: The study aim was to evaluate the ability of non-invasive inflammatory markers in exhaled breath to predict exacerbations of childhood asthma, and to assess the time course of changes in these exhaled markers before, during and after exacerbations. METHODS: The design was a prospective one-year longitudinal study. Regular two-month visits at the outpatient clinic were performed. Forty children with asthma (aged 6-16 years) participated. The primary outcome measure was the occurrence of an exacerbation. Assessment was made of the presence and severity of pulmonary symptoms, use of medication, and measurements of forced expiratory volume in 1 s using home monitor. The following independent parameters were assessed during outpatient visits: (1) exhaled nitric oxide, (2) inflammatory markers in exhaled breath condensate: acidity, nitrite, hydrogen peroxide, interleukin-1α, -5, -13, interferon-γ, (3) lung function, (4) asthma control score. RESULTS: Thirty-eight of 40 children completed the study. Sixteen children developed exacerbations, of which ten were moderate and six severe. Univariate Cox regression analysis revealed that condensate acidity, interleukin-5 and asthma control score were significant predictors of an asthma exacerbation (P < 0.05). In the multivariate Cox regression analysis, exacerbations were best predicted by the asthma control score and by the level of interleukin-5 in exhaled breath condensate (Wald scores of 7.19 and 4.44, P = 0.007 and P = 0.035 respectively). The predicted survival curve of this multivariate model showed a two times reduced risk on exacerbations in the category of children with the 10% most optimal values of IL-5 and asthma control score. CONCLUSIONS AND CLINICAL RELEVANCE: Both exhaled breath condensate interleukin-5 level and asthma control score were significant predictors of asthma exacerbations. These findings open up the possibility of assessing the potential of such parameters to titrate asthma treatment in future studies.

Increased number of cerebellar granule cells and astrocytes in the internal granule layer in sheep following prenatal intra-amniotic injection of lipopolysaccharide.

Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies.

Antenatal steroids and neonatal outcome after chorioamnionitis: a meta-analysis.

BACKGROUND: There is debate concerning the safety and efficacy of antenatal steroids in preterm labour with suspected intrauterine infection (chorioamnionitis). OBJECTIVES: We performed a systematic literature review and meta-analysis aimed at evaluating the efficacy and safety of antenatal steroids in clinical and histological chorioamnionitis. SEARCH STRATEGY: MEDLINE, EMBASE, BioMed Central and the Cochrane databases were searched using the terms 'chorioamnionitis OR intrauterine infection' and '*steroids OR *corticoids'. SELECTION CRITERIA: Studies that reported selected neonatal outcome measures in preterm infants with clinical or histological chorio-amnionitis, according to antenatal steroid exposure, were eligible. DATA COLLECTION AND ANALYSIS: Study selection, data extraction and data analysis were performed by two independent investigators. The meta-analysis techniques used included: Mantel-Haenszel analysis; an assessment of study heterogeneity using the Q statistic; and Egger's regression test and funnel plots, to assess publication bias. MAIN RESULTS: Seven observational studies were included. In histological chorioamnionitis (five studies), antenatal steroids were associated with reduced mortality (OR = 0.45; 95% CI = 0.30-0.68; P = 0.0001), respiratory distress syndrome (OR = 0.53; 95% CI = 0.40-0.71; P < 0.0001), patent ductus arteriosus (OR = 0.56; 95% CI = 0.37-0.85; P = 0.007), intraventricular haemorrhage (IVH; OR = 0.35; 95% CI = 0.18-0.66; P = 0.001) and severe IVH (OR = 0.39; 95% CI = 0.19-0.82; P = 0.01). In clinical chorioamnionitis (four studies), antenatal steroids were associated with reduced severe IVH (OR = 0.29; 95% CI = 0.10-0.89; P = 0.03) and periventricular leucomalacia (OR = 0.35; 95% CI = 0.14-0.85; P = 0.02). CONCLUSIONS: Antenatal steroids may be safe and reduce adverse neonatal outcome after preterm birth associated with chorioamnionitis. There is a need for randomised clinical trials to address this issue.

Increased cytokines, chemokines and soluble adhesion molecules in exhaled breath condensate of asthmatic children.

BACKGROUND: Airway inflammation in asthma is characterized by the production of cytokines, chemokines and soluble adhesion molecules. The assessment of these inflammatory biomarkers in exhaled breath condensate (EBC) is hampered by low detection rates. However, the use of a glass condenser system combined with a sensitive analytical technique may increase the possibility to assess these biomarkers in EBC in a reliable way. OBJECTIVE: (1) To assess the detection rates of cytokines (IL-1alpha, -1beta, -2, -4, -5, -6, -10, -12p70, -13, -18, IFN-gamma, TNF-alpha), chemokines [MIP1alpha (CCL3), MIF, eotaxin (CCL11), RANTES (CCL5), IP10 (CXCL10), IL8 (CXCL8), MCP1] and soluble adhesion molecules [soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM)] in EBC of children with asthma and healthy control children; (2) To study the differences in the biomarker concentration between children with asthma and controls. METHODS: Sixty children were included: 31 asthmatics (71% atopic) and 29 controls. Exhaled breath condensate was collected using a glass condenser system. The inflammatory markers (IM) were analysed using multiplex immunoassay technology. RESULTS: Detection percentages of cytokines, chemokines and adhesion molecules ranged from 94% to 100%, except for eotaxin (CCL11) and RANTES (CCL5) (detection rates of 10% and 45% in healthy controls, respectively). The intra-subject variability of biomarkers in EBC in the group as a whole ranged from 5.2% to 35.0%. In asthmatics, the levels of cytokines (IL-2, -4, -5, -6, -13, IFN-gamma), chemokines (MIP1alpha [CCL3], MIF, RANTES [CCL5], IP10 [CXCL10], IL8 [CXCL8], MCP1) and adhesion molecules (sICAM, sVCAM) were significantly increased in comparison with controls (P<0.05). CONCLUSION: If collected with a glass condenser and analysed by multiplex immunoassay technology, cytokines, chemokines and soluble adhesion molecules can be reliably demonstrated in EBC of children. Most of these IM were elevated in EBC of asthmatics compared with controls.

Increased blood pressure and impaired endothelial function after accelerated growth in IVF/ICSI children.

STUDY QUESTION: What is the effect of growth velocity (height and weight) in early infancy on metabolic end-points and endothelial function in children born after ART? SUMMARY ANSWER: Neonatal, infant and childhood growth is positively related to blood pressure in 9-year-old IVF/ICSI offspring, while growth in childhood was negatively associated with endothelial function. WHAT IS KNOWN ALREADY: Offspring of pregnancies conceived after ART are at risk for later cardiometabolic risk factors. It is well established that early growth is related to numerous later cardiometabolic risk factors such as high blood pressure. This concept is known as the Developmental Origin of Health and Disease theory. STUDY DESIGN SIZE DURATION: The relation between early growth and later cardiometabolic risk profile was studied in the MEDIUM-KIDS study, a prospective observational cohort study in children born after an IVF/ICSI treatment. In 131 children (48.1% males) at the average age of 9.4 years, cardiometabolic outcomes were assessed and growth data from birth until age 9 years were collected from child welfare centers. PARTICIPANTS/MATERIALS SETTINGS METHODS: The following cardiometabolic outcomes were assessed: blood pressure, skinfolds, lipid spectrum, hair cortisone and glucose and insulin levels. Data on maximum skin perfusion after transdermal delivery of acetylcholine as a measure of endothelial function were collected.Growth charts were obtained electronically from child welfare centers, which offer free consultations and vaccinations to all Dutch children. At these centers, height and weight are recorded at predefined ages. Growth was defined as z-score difference in weight between two time points. Multivariable linear regression analysis was used to model the relation between growth and cardiometabolic outcomes. The following growth windows were -studied simultaneously in each model: 0-1 month, 1-3 months, 3-6 months, 6-11 months, 11-24 months and 2-6 years. The model was adjusted for height growth in all intervals except for 0-1 month. MAIN RESULTS AND THE ROLE OF CHANCE: In multivariable linear regression analyses, multiple growth windows were positively associated with blood pressure, for example growth from 2-6 years was significantly related to systolic blood pressure: B = 4.13, P = 0.005. Maximum skin perfusion after acetylcholine was negatively associated with height-adjusted weight gain from 2 to 6 years: B = -0.09 (log scale), P = 0.03. Several growth windows (weight 1-3 months, 3-6 months, 6-11 months, 11-24 months, 2-6 years) were positively linked with total adiposity. Lipids, glucose tolerance indices and cortisone were not related to growth. LIMITATIONS REASONS FOR CAUTION: This study is of modest size and of observational nature, and we did not include a control group. Therefore, we cannot assess whether the observed associations are causal. It is also not possible to analyze if our observations are specific for, or exacerbated in, the ART population. Ideally, a control group of naturally conceived siblings of IVF/ICSI children should simultaneously be studied to address this limitation and to assess the impact of the ART procedure without the influence of parental (subfertility) characteristics. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study contribute to our understanding of the reported increased risk for hypertension in ART offspring. We speculate that early, accelerated growth may be involved in the reported increased risk for hypertension in ART offspring, with endothelial dysfunction as a possible underlying mechanism. However, additional research into the mechanisms involved is required. STUDY FUNDING/COMPETING INTERESTS: The study was financially supported by the March of Dimes, grant number #6-FY13-153. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the paper. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: NTR4220.

Erratum: Increased blood pressure and impaired endothelial function after accelerated growth in IVF/ICSI children.

[This corrects the article DOI: 10.1093/hropen/hoz037.].

Biomarker reproducibility in exhaled breath condensate collected with different condensers.

Optimal collection and analysis of exhaled breath condensate (EBC) are prerequisites for standardisation and reproducibility of assessments. The present study aimed to assess reproducibility of EBC volume, hydrogen peroxide (H(2)O(2)), 8-isoprostane and cytokine measurements using different condensers, including a newly developed glass condenser. At four points in time, 30 healthy subjects performed sequential EBC collections randomly using the following four condensers: glass, silicone, EcoScreen (Erich Jaeger GmbH, Hoechberg, Germany) and an optimised glass condenser. In small EBC samples, H(2)O(2) was measured by spectrophotometer, 8-isoprostane by enzyme immunoassay, and cytokines by multiplexed xMAP technology (Luminex Corporation, Austin, TX, USA). The optimised glass condenser yielded significantly more EBC volume (median 2,025 microL, interquartile range 1,600-2,525). The reproducibility of EBC volume, yielded by the new glass condenser, was comparable with EcoScreen (19-20 coefficients of variation (CV)%), but was significantly better compared with silicone and glass (29-37 CV%). The new condenser was associated with significantly more detections of H(2)O(2), 8-isoprostane, interleukin-2, -4, -5 and -13, and tumour necrosis factor-alpha. Isoprostane concentrations were significantly higher using the new condenser, whereas H(2)O(2) and cytokine concentrations were not. Reproducibility of biomarkers was equally variable for all condenser types. In conclusion, significantly more exhaled breath condensate volume and biomarker detections were found using the optimised glass condenser, including higher 8-isoprostane levels. However, biomarker reproducibility in exhaled breath condensate in healthy adults was not influenced by the type of condenser.

[Medicinal management of pain and symptoms following the withdrawal of treatment in babies and children]. / Medicamenteuze pijn- en symptoombestrijding bij het staken van de behandeling bij pasgeborenen en kinderen.

We present three cases to illustrate the end-of-life care after withdrawal of mechanical ventilation. In a one-year-old girl with meningococcal septic shock, muscle relaxants were continued when mechanical ventilation was withdrawn. In a 10-day-old girl with perinatal asphyxia a high dose of fentanyl was given before mechanical ventilation was withdrawn. A 6-week-old girl in a vegetative state was fighting for breath after detubation. At the request of the parents to end this condition, vecuronium bromide was given. In these three cases death was probably brought forward by a maximum of 12-24 hours. Three arguments can be presented to justify this: the relief of suffering, the perceptions of the parents and the fact that death was expected within a very short time. The administration of these medicines cannot, however, be considered normal medical practice. Therefore we argue that these cases should be reviewed by the national expert review committee and guidelines should be developed for appropriate palliative care after the withdrawal ofmechanical ventilation.

[Persistent pulmonary hypertension in a neonate caused by blood aspiration following vaginal blood loss]. / Persisterende pulmonale hypertensie bij een neonaat door bloedaspiratie ten gevolge van vaginaal bloedverlies.

A preterm neonate, with a gestational age of 30 1/7 weeks, was born after a period of prolonged rupture of the membranes and a retroplacental haematoma causing vaginal bleeding. During admission to the neonatal intensive-care unit, mechanical ventilation was indicated because of acute respiratory failure following blood aspiration, which was causing oxygenation and ventilation problems. Endotracheal surfactant was administered and, because of persistent pulmonary hypertension of the newborn (PPHN), NO-inhalation therapy was started. A quick recovery was seen and two days post partum the patient could be extubated. Blood aspiration may cause acute respiratory problems and PPHN, with quick recovery after effective mechanical ventilation, surfactant and NO-inhalation therapy.

[Tobacco control policies and perinatal health]. / Tabaksontmoediging en perinatale gezondheid.

OBJECTIVE: Study the association between the introduction of tobacco control policies in the Netherlands and changes in perinatal outcomes. DESIGN: National quasi-experimental study. METHOD: We used Netherlands Perinatal Registry data (now called Perined) for the period 2000-2011. We studied whether the introduction of smoke-free legislation in workplaces plus a tobacco tax increase and mass media campaign in January 2004, and extension of the smoke-free law to the hospitality industry accompanied by another tax increase and media campaign in July 2008, was associated with changes in perinatal outcomes. We studied all singleton births (gestational age: 24+0 to 42+6 weeks). Our primary outcome measures were: perinatal mortality, preterm birth and being small-for-gestational-age (SGA). Interrupted time series logistic regression analyses were performed to investigate changes in these outcomes occurred after the introduction of the aforementioned tobacco control policies (ClinicalTrials.gov: NCT02189265). RESULTS: Among 2,069,695 singleton births, 13,027 (0.6%) perinatal deaths, 116,043 (5.6%) preterm live-births and 187,966 (9.1%) SGA live-births were observed. The policies introduced in January 2004 were not associated with significant changes in any of the primary outcome measures. A -4.4% (95% CI: -6.4 to -2.4; p < 0.001) decrease in odds of a SGA birth was observed after the policy extension in July 2008 to include a smoke-free hospitality industry, a further tax increase and another media campaign. This translates to an estimated over 500 cases of SGA being averted per year. CONCLUSION: A reduction in SGA births, but not preterm birth or perinatal mortality, was observed in the Netherlands after extension of the smoke-free workplace law to include bars and restaurants, in conjunction with a tax increase and media campaign in 2008.

Sustained inflation: Prophylactic or rescue maneuver?

Application of nasal continuous positive airway pressure (nCPAP) in the delivery room is a valid alternative to mechanical ventilation in the management of respiratory failure of preterm infants, with reduced occurrence of bronchopulmonary dysplasia and death. nCPAP at birth is still burdened by a high failure rate. Sustained inflation appears to be an intriguing approach to allow the respiratory transition at birth by clearing the lung fluid, thus obtaining an adequate functional residual capacity. This may enhance nCPAP success. Sustained inflation reduces the need for mechanical ventilation in the first 72 h of life, with no changes in the incidence of bronchopulmonary dysplasia and death. The efficacy of sustained inflation seems to be related to the presence of open glottis with active breathing of the infant. Further studies are needed to recommend the application of sustained inflation during delivery room management of preterm infants at risk of respiratory distress or with clinical signs of respiratory failure.

Cyclic AMP-dependent protein kinase does not regulate CTP:phosphocholine cytidylyltransferase activity in maturing type II cells.

CTP:phosphocholine cytidylyltransferase catalyses a rate regulatory step in the de novo synthesis of surfactant phosphatidylcholine in alveolar type II cells. To investigate if cytidylyltransferase can be regulated by cAMP-dependent protein kinase, we first studied the ontogeny of cAMP-dependent protein kinase activity in type II cells of fetal rat lung. Total cAMP-dependent protein kinase activity, measured in the presence of 10 microM cAMP, as well as endogenous activity, measured without cAMP, increased with advancing gestation. Phosphocholine cytidylyltransferase activity showed a similar developmental profile. This temporal relationship between cAMP-dependent protein kinase and cytidylyltransferase supports a potential role for cAMP-dependent protein kinase in regulating cytidylyltransferase phosphorylation. Cytidylyltransferase purified from adult rat lung was, indeed, phosphorylated in vitro by cAMP-dependent protein kinase. Despite the phosphorylation, however, no change in cytidylyltransferase activity was noted. Pre-incubation of fetal type II cell cytosol with ATP and Mg2+ did not affect cytidylyltransferase activity. Addition of either cAMP, dibutyryl-cAMP or the catalytic subunit of cAMP-dependent protein kinase to the pre-incubation medium did also not alter cytidylyltransferase activity. Furthermore, neither cAMP-dependent protein kinase inhibitor peptide, nor H8, a cyclic nucleo-dependent protein kinase inhibitor, affected cytidylyltransferase activity in fetal type II cell cytosol. Treatment of intact fetal type II cells with either cAMP, dibutyryl-cAMP or 8-[4-chlorophenylthio]cAMP activated cAMP-dependent protein kinase activity but did not alter cytidylyltransferase activity. We conclude that the increase in cytidylyltransferase activity in fetal type II cells at late gestation is not regulated by the developmental activation of cAMP-dependent protein kinase.

Influence of phosphatidylglycerol on the uptake of liposomes by alveolar cells and on lung function.

The effect of phosphatidylglycerol on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages as well as the effect on endogenous surfactant function was studied in vivo. Healthy ventilated rats were intratracheally instilled with fluorescent labeled liposomes with different concentrations of phosphatidylglycerol. Lung function was determined by monitoring arterial oxygenation and, at the end of the experiment, by recording static pressure-volume curves. In addition, alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that, in the presence of cofactors (Ca(2+), Mg(2+)), phosphatidylglycerol stimulates the uptake by alveolar macrophages but hardly affects the uptake by alveolar type II cells. High concentrations of phosphatidylglycerol reduce the number of alveolar macrophages in the alveolar space and deteriorate lung function. On the other hand, the presence of cofactors protects the lung against the negative effects of phosphatidylglycerol on endogenous surfactant and alveolar macrophages. This study indicates that the phosphatidylglycerol concentration may play a fundamental role in the surfactant function and metabolism depending on the presence of so-called cofactors like calcium and magnesium; further study is needed to clarify the mechanisms involved.

Predictors of Ominous Outcome in Infants Undergone to Cardiac Surgery and Cardiopulmonary by-Pass: S100B Protein.

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined time-points before during and after surgery. In all CHD children, S100B values showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the surgical procedure. Moreover, S100B concentrations in CHD death group were significantly higher (P<0.01) than controls at all monitoring time-points. The ROC curve analysis showed that S100B measured before surgical procedure was the best predictor of perioperative death, among a series of clinical and laboratory parameters, reaching at a cut-off of 0.1 µg/L a sensitivity of 100% and a specificity of 63.7%. The present data suggest that in CHD infants biochemical monitoring in the perioperative period is becoming possible and S100B can be include among a series of parameters for adverse outcome prediction.

Endogenous brain protection: what the cerebral transcriptome teaches us.

Despite efforts to reduce mortality caused by stroke and perinatal asphyxia, these are still the 2nd largest cause of death worldwide in the age groups they affect. Furthermore, survivors of cerebral hypoxia-ischemia often suffer neurological morbidities. A better understanding of pathophysiological mechanisms in focal and global brain ischemia will contribute to the development of tailored therapeutic strategies. Similarly, insight into molecular pathways involved in preconditioning-induced brain protection will provide possibilities for future treatment. Microarray technology is a great tool for investigating large scale gene expression, and has been used in many experimental studies of cerebral ischemia and preconditioning to unravel molecular (patho-) physiology. However, the amount of data across microarray studies can be daunting and hard to interpret which is why we aim to provide a clear overview of available data in experimental rodent models. Findings for both injurious ischemia and preconditioning are reviewed under separate subtopics such as cellular stress, inflammation, cytoskeleton and cell signaling. Finally, we investigated the transcriptome signature of brain protection across preconditioning studies in search of transcripts that were expressed similarly across studies. Strikingly, when comparing genes discovered by single-gene analysis we observed only 15 genes present in two studies or more. We subjected these 15 transcripts to DAVID Annotation Clustering analysis to derive their shared biological meaning. Interestingly, the MAPK signaling pathway and more specifically the ERK1/2 pathway geared toward cell survival/proliferation was significantly enriched. To conclude, we advocate incorporating pathway analysis into all microarray data analysis in order to improve the detection of similarities between independently derived datasets.

Mesenteric artery reactivity and small intestine morphology in a chicken model of hypoxia-induced fetal growth restriction.

Infants with intrauterine growth retardation are prone to intestinal disorders. The morphological and molecular mechanisms that lead to these complications are not completely understood and suitable experimental models are necessary. The aim of this study was to characterize mesenteric artery (MA) reactivity, small intestine morphometry and intestinal expression of vascular endothelial growth factor (VEGF) in a chicken model of hypoxia-induced fetal growth restriction. Chicken embryos (15 and 19 incubation days) and hatchlings (<3-h-old and 1-d-old) were incubated under hypoxic (15% O2 from day 0 to day 19 of incubation) or normoxic conditions. Vascular reactivity was studied using wire miography. Intestinal morphometry was assessed in hematoxyline-eosine-stained sections. VEGF mRNA expression was determined by RT-PCR analysis. Hypoxia increased the responsiveness of chicken embryo MAs to the adrenergic agonist norepinephrine, the polypeptide endothelin (ET)-1, and the nitric oxide donor sodium nitroprusside and decreased the responsiveness to the endothelium-dependent relaxant agonist acetylcholine. However, the majority of these alterations, with the exception of the hyperresponsiveness to ET-1, were not present in the hypoxic hatchlings. When intestinal histology was analyzed, subtle hypoxia-induced changes were noted in the villi and the muscularis propria from the hatchlings. Hypoxic incubation also diminished the expression of VEGF mRNA in the terminal ileum of the hatchlings. In conclusion, chronic moderate hypoxia during incubation results in subtle but significant alterations in chicken MA reactivity, small intestine morphology and VEGF expression. Whether these alterations may have a direct effect on the functional status of the intestine remains to be investigated.

Antenatal exposure to chorioamnionitis affects lipid metabolism in 7-week-old sheep.

Antenatal exposure of the fetus to inflammation may alter postnatal organ development. In our previous work, we demonstrated that the fetal liver is involved in the systemic inflammation associated with chorioamnionitis, leading to metabolic changes. On the basis of these findings, we hypothesized that chorioamnionitis can lead to postnatal inflammation-related liver injury and disturbed lipid metabolism. Chorioamnionitis was induced in sheep by intra-amniotic injection of lipopolysaccharide (LPS) or saline at 90, 100 and 110 days of gestation. Liver homeostasis and lipid metabolism were analyzed at term and at 7 weeks of age. At term, hepatic T-lymphocytes and apoptotic hepatocytes were increased. In addition, hepatic cholesterol and triglyceride levels were decreased in LPS-exposed animals compared with controls. At 7 weeks of age, no hepatic inflammation could be detected. However, liver triglycerides and plasma cholesterol levels were increased in LPS-exposed animals relative to controls. The changes in lipid levels at 7 weeks of age were associated with increased leptin receptor mRNA levels, increased lipid peroxidation, increased expression of cytochrome c oxidase subunit 4 as a marker for mitochondrial function and increased circulating ceramide levels. These findings demonstrate that chorioamnionitis-mediated antenatal inflammation-related liver disturbances have long-lasting postnatal effects on lipid metabolism.