Can the biology of VEGF and haem oxygenases help solve pre-eclampsia?

Pre-eclampsia, a pregnancy-specific multi-organ syndrome characterized by widespread endothelial damage, is a new risk factor for cardiovascular disease. No therapies exist to prevent or treat this condition, even to achieve a modest improvement in pregnancy length or birth weight. Co-administration of soluble VEGFR-1 [VEGF (vascular endothelial growth factor) receptor-1; more commonly known as sFlt-1 (soluble Fms-like tyrosine kinase-1)] and sEng (soluble endoglin) to pregnant rats elicits severe pre-eclampsia-like symptoms. These two anti-angiogenic factors are increased dramatically prior to the clinical onset of pre-eclampsia and are quite possibly the 'final common pathway' responsible for the accompanying signs of hypertension and proteinuria as they can be reversed by VEGF administration in animal models. HO-1 (haem oxygenase-1), an anti-inflammatory enzyme, and its metabolite, CO (carbon monoxide), exert protective effects in several organs against oxidative stimuli. In a landmark publication, we showed that the HO-1 pathway inhibits sFlt-1 and sEng in cultured cells and human placental tissue explants. Both CO and NO (nitric oxide) promote vascular homoeostasis and vasodilatation, and activation of VEGFR-1 or VEGFR-2 induced eNOS (endothelial nitric oxide synthase) phosphorylation, NO release and HO-1 expression. Our studies established the HO-1/CO pathway as a negative regulator of cytokine-induced sFlt-1 and sEng release and eNOS as a positive regulator of VEGF-mediated vascular morphogenesis. These findings provide compelling evidence for a protective role of HO-1 in pregnancy and identify it as a target for the treatment of pre-eclampsia. Any agent that is known to up-regulate HO-1, such as statins, may have potential as a therapy. Any intervention achieving even a modest prolongation of pregnancy or amelioration of the condition could have a significant beneficial health impact worldwide.

Risk factors for type 2 diabetes mellitus and cardiovascular diseases in Hispanic adolescents

This cross-sectional study evaluated risk factors (RF) for type 2 diabetes (T2DM) and cardiovascular diseases (CVD) in 100 Hispanic adolescents(50 overweight, 50 non-overweight) aged 12-16 years, and their associations with body mass index (BMI), diet, physical activity (PA), gender, and birth weight (BW). The RF studied were fasting plasma glucose (FPG), insulin sensitivity (IS), total cholesterol (TC), triacylglycerols (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), acanthosis nigricans (AN), and blood pressure (BP). Dietary intakes were assessed using the Block Kids Questionnaire, fat-related intake behavior (FB) using the Fat-Related Diet Habits Questionnaire, and PA using the Modifiable Activity Questionnaire for Adolescents. Blood was collected after an overnight fast of 12 hours. All statistical analyses used SPSS 14.0. Overweight adolescents had presence of AN, higher BP, TC, TG, and LDL, and lower IS, ps < .001, as compared to non-overweight adolescents. Overweight adolescents were more likely to have 1 and 2 RF for T2DM and CVD as compared to having 0, ps < .001, and 2 RF as compared to having 1, p =.033. Adolescents with kilocalorie (Kcal) intake above requirements for age gender, and PA level were 4.6 times more likely to be overweight, p = .005. Overweight adolescents had worse FB, p = .011, and lower PA, p < .001. Adolescents with worse FB had higher BP, p = .016. Fiber below recommendations (14g/1,000 Kcal) was associated with being overweight, p = .012, and lower IS, p = .040. Adolescents with higher BW had higher FPG, p = .013. Our findings point to an association between being overweight and RF for T2DM and CVD, suggesting that overweight during adolescence may have serious health consequences for Hispanic adolescents. Also, our results indicate that Hispanic overweight adolescents eat more Kcal and less fiber than required, have worst FB, and less PA levels than their non-overweight counterparts. In addition, high BW and dietary habits of Hispanic adolescents, such as low fiber and FB, increase their risk for T2DM and CVD. We conclude that BMI can serve as a useful tool to identify Hispanic adolescents at risk for T2DM and CVD.

Avaliação do ganho de peso de bebês prematuros em relação ao leite materno cru e leite pasteurizado

This study aims to evaluate the weight gain of premature newborns fed with breast milk from their mothers' from those that are fed with breast milk from the milk bank. The research is the quantitative, descriptive and observational kind. It was conducted in the Neonatal Intensive Care Unit and Housing from the Maternity Hospital Escola Januário Cicco (MEJC), that is a reference for high risk pregnancy and birth in Rio Grande do Norte. The premature newborns included were following these parameters: gestational age from 26 to 37 weeks, initially hospitalized at UTIN, with oral diet, by means by gavage, cup and/or suction. Studies with premature newborns with a zero diet longer than seven days or complications that interfered in the evaluation of weight gain were excluded from this study. The sample was selected for convenience and had data of all newborns hospitalized at UTIN from the May to June of 2014 time period, followed to their discharge, ended by August of 2014 and had the inclusion parameters of the study. From the period of the data collection, 60 premature newborns entered the maternity and 39 of those were the sample of research. The project was approved by the Research Ethics Committee from UFRN, under CAAE nº 0699.0.000.294-11. The data was analyzed by means of descriptive and deduced statistics. The results indicated that the involved in the study, were born from mother with average age of 25,36 years, with less than nine years education 21 (53,8%), had the family income less than a minimum wage 24 (61,5%). Among the newborn, the female gender predominated 20 (51,3%), had cesarean delivery 25 (64,1%), had moderate prematurity 29 (74,5%), more of 1.500g 22 (556,4%). The birth weight average was 1.608,49g. The total of diets were 9.994, and an average of 256 for each newborn, in a 32,12 days of hospitalization time period. Most of the diet supplies were from the breast milk bank (50,34%), however 56,4% of the newborns had most of the diet from their mothers' milked breast milk. It was detected that 38,5% of the newborns had, in some given moment, artificial milk. The daily weight gain average of all newborns was 2,59g, but 35% of them had an average above 10g per day. From the newborn's group (n=25) that had medium weight gain, only 9 of them (36,0%) received mainly their own mothers' milked breast milk. It's been conclusive that most of the premature newborns gained weight predominantly from diets from the breast milk of the Milk Bank, showing the need of a bigger incentive to exclusive breast feeding.

Segurança do paciente em terapia intensiva neonatal: identificação e análise de eventos adversos

The patient safety is a major concern in health services for its global dimension, as evidenced by the fragility of care processes that predispose an occurrence of adverse events. These events in a neonatal intensive care unit are considered serious and hazardous to lives of newborns. The present study aimed to identify and analyze adverse events in a neonatal intensive care unit based in Trigger Tool. It is an epidemiological, cross-sectional , exploratory, retrospective study with quantitative, descriptive and analytical approach, performed in 2015 at a school hospital. The sample was not probabilistic, involving 116 newborns who met the eligibility criteria. Data collection was performed by retrospective review of medical records, using a specific kind of "trigger" instrument, composed of sentinel events in neonatology, adapted from the American model used by the Vermont-Oxford Network. Data were analyzed using descriptive and inferential statistics. The chi-square test for linear trend was used to assess the associations between the variables of interest. The research received a favorable agreement from Ethics Committee of the Federal University of Rio Grande do Norte, under number 1055533, and Presentation Certificate for Ethics Assessment 43894515.6.0000.5537. The results show among investigated newborns, 110 experienced at least one adverse event during their stay, with a total of 391 medical records analyzed and rate of 3.37 events per patient. Prevailed the preterm newborns with low birth weight, from mother who had hypertensive diseases during pregnancy and urinary tract infection. The average hospitalization time was 25 days, associated with hospital-acquired infections events (p = 0.01). Among the identified adverse events stood out the events related to thermoregulation disorders (39.0%), with prevalence of hypothermia (26.0%), followed by health care-related infections (16.4%) and blood glucose disorders, hypoglycemia (9.00%) and hyperglycemia (6.64%). Most of these incidents were classified in categories E and F, which represents that there was damage small proportion. Due to these damages come from the care practice with newborn, 78% were classified as avoidable. There was statistically significant association between the variable birth weight with infections (p = 0.006) as well as peri/intraventricular bleeding (p = 0.02), hypoglycemia (p = 0.021), hyperglycemia (p = 0.001), hyperthermia (p = 0.39) and death (p=0,02). Gestational age was associated with seizures (p = 0.002), hyperglycemia (p=0.017) e hyperthermia (p=0.027). The security institution culture was reported by the health workers as intermediate, even though the number of adverse events found in only one unit of service indicates that there is much to be done. Thus the high rate of adverse events identified in the neonatal intensive care unit reinforces the necessity to elaborate specific preventive strategies for this risk environment.

Segurança do paciente em terapia intensiva neonatal: identificação e análise de eventos adversos

The patient safety is a major concern in health services for its global dimension, as evidenced by the fragility of care processes that predispose an occurrence of adverse events. These events in a neonatal intensive care unit are considered serious and hazardous to lives of newborns. The present study aimed to identify and analyze adverse events in a neonatal intensive care unit based in Trigger Tool. It is an epidemiological, cross-sectional , exploratory, retrospective study with quantitative, descriptive and analytical approach, performed in 2015 at a school hospital. The sample was not probabilistic, involving 116 newborns who met the eligibility criteria. Data collection was performed by retrospective review of medical records, using a specific kind of "trigger" instrument, composed of sentinel events in neonatology, adapted from the American model used by the Vermont-Oxford Network. Data were analyzed using descriptive and inferential statistics. The chi-square test for linear trend was used to assess the associations between the variables of interest. The research received a favorable agreement from Ethics Committee of the Federal University of Rio Grande do Norte, under number 1055533, and Presentation Certificate for Ethics Assessment 43894515.6.0000.5537. The results show among investigated newborns, 110 experienced at least one adverse event during their stay, with a total of 391 medical records analyzed and rate of 3.37 events per patient. Prevailed the preterm newborns with low birth weight, from mother who had hypertensive diseases during pregnancy and urinary tract infection. The average hospitalization time was 25 days, associated with hospital-acquired infections events (p = 0.01). Among the identified adverse events stood out the events related to thermoregulation disorders (39.0%), with prevalence of hypothermia (26.0%), followed by health care-related infections (16.4%) and blood glucose disorders, hypoglycemia (9.00%) and hyperglycemia (6.64%). Most of these incidents were classified in categories E and F, which represents that there was damage small proportion. Due to these damages come from the care practice with newborn, 78% were classified as avoidable. There was statistically significant association between the variable birth weight with infections (p = 0.006) as well as peri/intraventricular bleeding (p = 0.02), hypoglycemia (p = 0.021), hyperglycemia (p = 0.001), hyperthermia (p = 0.39) and death (p=0,02). Gestational age was associated with seizures (p = 0.002), hyperglycemia (p=0.017) e hyperthermia (p=0.027). The security institution culture was reported by the health workers as intermediate, even though the number of adverse events found in only one unit of service indicates that there is much to be done. Thus the high rate of adverse events identified in the neonatal intensive care unit reinforces the necessity to elaborate specific preventive strategies for this risk environment.

A desigualdade espacial do Baixo Peso ao Nascer no Brasil

Low birth weight (LBW) is a risk factor for neonatal and infant morbidity and mortality. In Brazil the highest percentages of low birth weight occur in regions of higher socio-economic status. The scope of this article is to ascertain the spatial distribution of low birth weight rates and the correlation with social and service indicators. The scale is ecological taking all the Brazilian states as units of analysis. The spatial analysis technique is the methodology used together with data from SINASC, IPEA and IBGE for 2009. Higher rates of low birth weight are found in the south/southeastern states (Global Moran: 0.267, p = 0.02). Clusters of the high-high type in the Southeast and of the low-low variety in states in the Amazon region are detected. The spatial inequality of low birth weight reflects the socio-economic conditions of the states. More developed regions have higher rates of low birth weight, therefore, the presence of the service and its use decrease infant mortality and increase LBW.

Impacto na epidemiologia da sepse tardia após a mudança do protocolo de antimicrobianos em uma UTIN de um serviço universitário

Advances in neonatology resulted in reducing the mortality rate and the consequent increase in survival of newborn pre terms (PTN). On the other hand, there was also a considerable increase in the risk of developing health care-related infection (HAI) in its most invasive, especially for bloodstream. This situation is worrying, and prevent the occurrence of it is a challenge and becomes one of the priorities in the Neonatal Intensive Care Unit (NICU). Sepsis is the main cause of death in critical neonates and affects more than one million newborns each year, representing 40% of all deaths in neonates. The incidence of late sepsis can reach 50% in NICUs. Currently the major responsible for the occurrence of sepsis in developed countries is the coagulase negative Staphylococcus (CoNS), followed by S. aureus. The cases of HAIs caused by resistant isolates for major classes of antimicrobial agents have been increasingly frequent in the NICU. Therefore, vancomycin has to be prescribed more frequently, and, today, the first option in the treatment of bloodstream infections by resistant Staphylococcus. The objectives of this study were to assess the impact on late sepsis in epidemiology III NICU after the change of the use of antimicrobials protocol; check the frequency of multiresistant microorganisms; assess the number of neonates who came to death. This study was conducted in NICU Level III HC-UFU. three study groups were formed based on the use of the proposed late sepsis treatment protocol, with 216 belonging to the period A, 207 B and 209 to the C. The work was divided into three stages: Period A: data collected from neonates admitted to the unit between September 2010 to August 2011. was using treatment of late sepsis: with oxacillin and gentamicin, oxacillin and amikacin, oxacillin and cefotaxime. Period B: data were collected from March 2012 to February 2013. Data collection was started six months after protocol change. Due to the higher prevalence of CoNS, the initial protocol was changed to vancomycin and cefotaxime. Period C: data were collected from newborns inteerne in the unit from September 2013 to August 2014. Data collection was started six months after the protocol change, which occurred in March 2013. From the 632 neonates included in this study, 511 (80,8%) came from the gynecology and obstetrics department of the HC-UFU. The mean gestational age was 33 weeks and the prevailing sex was male (55,7%). Seventy-nine percent of the studied neonates were hospitalized at the NICU HC-UFU III because of complications related to the respiratory system. Suspicion of sepsis took to hospitalization in the unit of 1,9% of newborns. In general, the infection rate was 34,5%, and the most frequent infectious sepsis syndrome 81,2%. There was a tendency to reduce the number of neonates who died between periods A 11 and C (p = 0,053). From the 176 cases of late sepsis, 73 were clinical sepsis and 103 had laboratory confirmation, with greater representation of Gram positive bacteria, which corresponded to 67.2% of the isolates and CoNS the most frequent micro-organism (91,5%). There was a statistically significant difference in the reduction of isolation of Gram positive microorganisms between periods A and C (p = 0,0365) as well as in reducing multidrug-resistant CoNS (A and B period p = 0,0462 and A and C period, p = 0,158). This study concluded that: the CoNS was the main microorganism responsible for the occurrence of late sepsis in neonates in the NICU of HC-UFU; the main risk factors for the occurrence of late sepsis were: birth weight <1500 g, use of PICC and CUV, need for mechanical ventilation and parenteral nutrition, SNAPPE> 24 and length of stay more than seven days; the new empirical treatment protocol late sepsis, based on the use of vancomycin associated cefepime, it was effective, since promoted a reduction in insulation CoNS blood cultures between the pre and post implementation of the Protocol (A and C, respectively); just as there was a reduction in the number of newborns who evolved to death between periods A and C.

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

Dysregulation of placental cystathionine-β-synthase impact on fetal growth restriction

INTRODUCTION: Fetal growth restriction (FGR), which causes perinatal morbidity and mortality, is characterized by birth weight and body mass being below 10th percentile for gestational age. FGR babies are prone to develop cardiovascular diseases later in life. Inadequate placental transfer of nutrients from mother to fetus due to placental insufficiency is considered the underlying cause of FGR. Recently, we demonstrated that blockade of cystathionine-γ-lyase (CSE) activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in cystathionine-β-synthase (CBS) / H2S pathway may promote FGR. METHODS: Placental CBS expressions were determined in women with FGR (n=9) and normal controls (n=14) by Western blotting and real-time qPCR. ELISA was used to determine angiogenic factors levels in plasma and first-trimester (8–12 weeks gestation) human placental explants. Time pregnant mice were treated with CBS inhibitor, aminooxyacetic acid (AOA). Mean arterial blood pressure (MBP), histological assessments of placenta and embryos were performed. RESULTS: Placental CBS expressions were significantly reduced in women with FGR. Inhibition of CBS activity by AOA reduced PlGF production from first-trimester human placental explants, Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction, which was associated with reduced placental PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor-treated animals. Furthermore, H2S donor GYY4137 treatment restored fetal growth in pregnant mice exposed to high level of sFlt-1. CONCLUSIONS: These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia opening up the therapeutic potentials of H2S therapy in this condition.

The Antibiotic Resistance and Prescribing in European Children Project: A Neonatal and Pediatric Antimicrobial Web-based Point Prevalence Survey in 73 Hospitals Worldwide

BACKGROUND: The neonatal and pediatric antimicrobial point prevalence survey (PPS) of the Antibiotic Resistance and Prescribing in European Children project (http://www.arpecproject.eu/) aims to standardize a method for surveillance of antimicrobial use in children and neonates admitted to the hospital within Europe. This article describes the audit criteria used and reports overall country-specific proportions of antimicrobial use. An analytical review presents methodologies on antimicrobial use.

METHODS: A 1-day PPS on antimicrobial use in hospitalized children was organized in September 2011, using a previously validated and standardized method. The survey included all inpatient pediatric and neonatal beds and identified all children receiving an antimicrobial treatment on the day of survey. Mandatory data were age, gender, (birth) weight, underlying diagnosis, antimicrobial agent, dose and indication for treatment. Data were entered through a web-based system for data-entry and reporting, based on the WebPPS program developed for the European Surveillance of Antimicrobial Consumption project.

RESULTS: There were 2760 and 1565 pediatric versus 1154 and 589 neonatal inpatients reported among 50 European (n = 14 countries) and 23 non-European hospitals (n = 9 countries), respectively. Overall, antibiotic pediatric and neonatal use was significantly higher in non-European (43.8%; 95% confidence interval [CI]: 41.3-46.3% and 39.4%; 95% CI: 35.5-43.4%) compared with that in European hospitals (35.4; 95% CI: 33.6-37.2% and 21.8%; 95% CI: 19.4-24.2%). Proportions of antibiotic use were highest in hematology/oncology wards (61.3%; 95% CI: 56.2-66.4%) and pediatric intensive care units (55.8%; 95% CI: 50.3-61.3%).

CONCLUSIONS: An Antibiotic Resistance and Prescribing in European Children standardized web-based method for a 1-day PPS was successfully developed and conducted in 73 hospitals worldwide. It offers a simple, feasible and sustainable way of data collection that can be used globally.

The association between spastic Cerebral Palsy, intellectual impairment, and gestational age: results from the Northern Ireland Cerebral Palsy Register

Background
Studies suggest a complex relationship between Cerebral Palsy sub-types, severity of impairment, and risk factors such as gestational age. To investigate these relationships, we conducted analyses on over 1,100 children included in the Northern Ireland Cerebral Palsy Register (NICPR) whose clinical CP subtype was Bilateral Spastic or Spastic Hemiplegia, and for whom information was available on the relevant variables.
Methods
We tested for the association between Bilateral and Hemiplegia subtypes, severe intellectual impairment, and gestational age (term; moderately preterm; very or extremely preterm) while controlling for gender, socio-economic deprivation, year of birth, and birth weight (using a standardized birth-weight score based on deviance from the birth weight average within each gestational age band). Severity of intellectual impairment was dichotomised (severe intellectual delay vs. moderate or no delay).
Results
Logistic regressions indicated a good fit of the model, and the predictors included explained approximately 19% of variability in the outcome. The results indicated a strong association between the Bilateral subtype and severe intellectual impairment: compared to children with the Hemiplegia subtype, those with Bilateral Spastic CP displayed a 10-fold increase in the odds of severe intellectual impairment. The results revealed a significant interaction between CP subtype and gestational age: for the Bilateral CP subtype, being born at term was associated with increased probability of severe intellectual impairment.
Discussion
Results are consistent with other studies (Hemming et al., 2008) in indicating that the likelihood of cognitive impairments increases with increasing gestational age at delivery of Bilateral Spastic CP children. The results are discussed in light of hypotheses that suggest the brain might be able to reorganise and compensate the effects of lesions and injuries when it is still less developed.

Gestação após gastroplastia para tratamento de obesidade mórbida: série de casos e revisão da literatura

Objetivo: relatar a evolução de uma série de casos de gestação em mulheres previamente submetidas à cirurgia de bypass gástrico para tratamento de obesidade grave. Métodos: cinco casos consecutivos de gravidez após gastroplastia ocorridos entre 2001 e 2004 foram avaliados. As pacientes tinham idade entre 30 e 34 anos e todas haviam sido submetidas à cirurgia de Capella. Aspectos clínicos, laboratoriais e do acompanhamento materno e fetal foram considerados, durante o período gestacional e após o parto. Foi realizada revisão da literatura internacional, por meio das bases de dados MEDLINE e Web of Science, utilizando os seguintes unitermos: gastroplasty, gastric bypass surgery, bariatric surgery e pregnancy. Resultados: todas as gestações observadas foram únicas e não ocorreram complicações obstétricas, durante o seguimento pré-natal e parto. Também não houve registro de recém-nascidos prematuros ou de baixo peso ao nascimento. Conclusão: nossos dados sugerem que a gravidez após gastroplastia é segura para a mãe e feto. Entretanto, em virtude do limitado volume de informação disponível sobre o tema, investigações adicionais são necessárias para estabelecer recomendações apropriadas com relação ao seguimento dessas gestações _________________________________________________ABSTRACT Purpose: we report a small series of pregnant women who underwent gastric bypass surgery for severe obesity, with a review of the literature on this topic. Methods: five consecutive cases of pregnancy after gastroplasty between 2001 and 2004 were evaluated, and clinical, laboratory and therapeutic features were considered. Patients were 30 to 34 years old and all had been submitted to gastroplasty by the Capella technique. The outcomes for both the pregnant woman and the fetus were evaluated. A search of the English language literature was done through MEDLINE and Web of Science databases with the following terms: gastroplasty, gastric bypass surgery, bariatric surgery, and pregnancy. Results: all 5 pregnancies were singleton. No major obstetric complications were observed and there were no premature or lowbirth weight infants. Conclusion: our data suggest that pregnancy following gastroplasty is safe for mother and fetus. However, since information about this topic is limited, further investigations are required to establish appropriate recommendations concerning the follow-up of these pregnancies