Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Neonatal sepsis and Kawasaki disease.

The purpose of this study is to clarify the relationship between neonatal sepsis and future development of Kawasaki disease (KD). We analyzed data from the National Hospital Organization Neonatal Intensive Care Unit (NHO-NICU) registry study in Japan. Participants in this study were children with a history of hospitalization in the NICU at the participating institutions from 2010 to 2014. A questionnaire was administered at age 3 years to obtain information about the patient's history of KD. There were 8275 infants who were eligible for this study. At 3 years of age, parents of 2161 children responded to the follow-up survey (follow-up rate, 26.1%). Multivariate logistic regression analysis adjusted for preterm birth, sex, use of antibiotics in the NICU, parity, and maternal smoking showed that children with neonatal sepsis were more likely to have a history of KD at 3 years of age (adjusted odds ratio [aOR]: 11.67, 95% confidence interval [CI]: 2.84-47.96). CONCLUSIONS: Among infants admitted to the NICU, neonatal sepsis might be associated with development of KD later in life. Further large studies are needed to elucidate the relationship between neonatal infections and KD development. WHAT IS KNOWN: • Preterm birth is known to be a risk factor for Kawasaki disease. •It is not yet known which factors related to preterm birth increase the risk of developing Kawasaki disease. WHAT IS NEW: •Neonatal sepsis is associated with an increased risk of subsequent development of Kawasaki disease. •Antibiotic use in the neonatal intensive care unit may also be an independent risk factor for subsequent development of Kawasaki disease.

Noninfectious influencers of early-onset sepsis biomarkers.

Diagnostic tests for sepsis aim to either detect the infectious agent (such as microbiological cultures) or detect host markers that commonly change in response to an infection (such as C-reactive protein). The latter category of tests has advantages compared to culture-based methods, including a quick turnaround time and in some cases lower requirements for blood samples. They also provide information on the immune response of the host, a critical determinant of clinical outcome. However, they do not always differentiate nonspecific host inflammation from true infection and can inadvertently lead to antibiotic overuse. Multiple noninfectious conditions unique to neonates in the first days after birth can lead to inflammatory marker profiles that mimic those seen among infected infants. Our goal was to review noninfectious conditions and patient characteristics that alter host inflammatory markers commonly used for the diagnosis of early-onset sepsis. Recognizing these conditions can focus the use of biomarkers on patients most likely to benefit while avoiding scenarios that promote false positives. We highlight approaches that may improve biomarker performance and emphasize the need to use patient outcomes, in addition to conventional diagnostic performance analysis, to establish clinical utility.

Infección grave por estreptococo del grupo B en la Unidad de Cuidados Intensivos Pediátricos del Centro Hospitalario Pereira Rossell entre los años 2007 y 2017 / Serious infection due to group B Streptococcus at the Pediatric Intensive Care Unit of the Pereira Rossell Children's Hospital between 2007 and 2017 / Infecção grave causada por Estreptococo do grupo B na Unidade de Terapia Intensiva do Centro Hospitalar Pediátrico Pereira Rossell entre os anos 2007 e 2017

Introducción: el estreptococo del grupo B (EGB) es una causa frecuente de sepsis neonatal. La enfermedad precoz disminuyó su incidencia por la profilaxis antibiótica, a diferencia de la sepsis tardía, que aumentó su incidencia en los últimos años. Objetivo: conocer la incidencia de la sepsis tardía en el período 2016-2017 en el Centro Hospitalario Pereira Rossell (CHPR). El secundario, describir las características epidemiológicas y clínicas de sepsis tardía por EGB en niños ingresados a la Unidad de Cuidados Intensivos de Niños (UCIN) del CHPR en el período 2007-2017. Resultados: la incidencia calculada de sepsis tardía por EGB fue de 0,53 casos/1000 recién nacidos (RN) vivos. Entre los años 2007 y 2017 ingresaron cinco niños por sepsis tardía por EGB a la UCIN del CHPR. La presentación clínica más frecuentes fue fiebre sin foco y meningitis. Se obtuvieron tres aislamientos en sangre de EBG y tres en líquido cefalorraquídeo (dos en cultivo y otro por detección de ADN). Ninguno falleció. Los casos con meningitis presentaron alteraciones en la tomografía de cráneo. Un niño fue pretérmino. Conclusiones: la sepsis tardía se vincula a importante morbimortalidad en pediatría. No se ha establecido cuáles son los principales factores de riesgo asociados a una enfermedad grave ni las políticas para disminuir su incidencia.

Background: group B streptococcus (GBS) is a common cause of neonatal sepsis. Early disease decreased its incidence due to antibiotic prophylaxis. Late sepsis increased its incidence in recent years. Objectives: to know the incidence of late onset EGB sepsis in the period 2016-2017 at the Pereira Rossell Hospital Center (CHPR), and secondly, to describe the epidemiological characteristics and the clinical presentation of late onset sepsis due to GBS in children admitted to the Children's Intensive Care Unit (UCIN) of the CHPR in the period 2007-2017. Results: the calculated incidence of late sepsis due to GBS was 0.53 cases/1000 live newborns. Between 2007-2017, 5 children were admitted due to GBS late sepsis at the UCIN. The most frequent clinical presentation was fever without focus and meningitis. 3 isolates were obtained in EBG blood cultures and 3 in cerebrospinal fluid (2 in culture and another by DNA detection). None of them died. Cases with meningitis showed abnormalities in the brain tomography. 1 of the 5 was preterm. Conclusions: late sepsis is associated with significant morbidity and mortality in pediatric patients. The main risk factors associated with serious disease and the policies needed to reduce its incidence have not been established.

Introdução: o estreptococo do grupo B (SGB) é uma causa frequente de sepse neonatal. A doença precoce diminuiu sua incidência devido à profilaxia antibiótica, ao contrário da sepse tardia, que aumentou sua incidência nos últimos anos. Objetivo: conhecer a incidência de sepse tardia no período 2016-2017 no Centro Hospitalar Pereira Rossell (CHPR) e descrever as características epidemiológicas e clínicas da sepse tardia por SGB em crianças internadas na Unidade de Terapia Intensiva Infantil (UTIN) do CHPR no período de 2007-2017. Resultados: a incidência calculada de sepse tardia por SGB foi de 0,53 casos/1000 recém-nascidos vivos (RNs). Entre 2007-2017, 5 crianças foram internadas na UTIN do CHPR por sepse tardia devido a GBS. A apresentação clínica mais frequente foi febre sem causa e meningite. 3 isolados de EBG foram obtidos no sangue e 3 no líquido cefalorraquidiano (2 em cultura e outro por detecção de DNA). Nenhum dos pacientes morreu. Os casos com meningite apresentaram alterações na tomografia de crânio. Uma criança era pré-termo. Conclusões: a sepse tardia está associada a significativa morbimortalidade em pediatria. Os principais fatores de risco associados a uma doença grave e as políticas para reduzir sua incidência ainda não foram estabelecidas.

Clinical chorioamnionitis at term X: microbiology, clinical signs, placental pathology, and neonatal bacteremia - implications for clinical care.

OBJECTIVES: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intra-amniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia. METHODS: This retrospective cross-sectional study included 43 women with the diagnosis of clinical chorioamnionitis at term. The presence of microorganisms in the amniotic cavity was determined through the analysis of amniotic fluid samples by cultivation for aerobes, anaerobes, and genital mycoplasmas. A broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry was also used to detect bacteria, select viruses, and fungi. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL. RESULTS: (1) Intra-amniotic infection (defined as the combination of microorganisms detected in amniotic fluid and an elevated IL-6 concentration) was present in 63% (27/43) of cases; (2) the most common microorganisms found in the amniotic fluid samples were Ureaplasma species, followed by Gardnerella vaginalis; (3) sterile intra-amniotic inflammation (elevated IL-6 in amniotic fluid but without detectable microorganisms) was present in 5% (2/43) of cases; (4) 26% of patients with the diagnosis of clinical chorioamnionitis had no evidence of intra-amniotic infection or intra-amniotic inflammation; (5) intra-amniotic infection was more common when the membranes were ruptured than when they were intact (78% [21/27] vs. 38% [6/16]; p=0.01); (6) the traditional criteria for the diagnosis of clinical chorioamnionitis had poor diagnostic performance in identifying proven intra-amniotic infection (overall accuracy, 40-58%); (7) neonatal bacteremia was diagnosed in 4.9% (2/41) of cases; and (8) a fetal inflammatory response defined as the presence of severe acute funisitis was observed in 33% (9/27) of cases. CONCLUSIONS: Clinical chorioamnionitis at term, a syndrome that can result from intra-amniotic infection, was diagnosed in approximately 63% of cases and sterile intra-amniotic inflammation in 5% of cases. However, a substantial number of patients had no evidence of intra-amniotic infection or intra-amniotic inflammation. Evidence of the fetal inflammatory response syndrome was frequently present, but microorganisms were detected in only 4.9% of cases based on cultures of aerobic and anaerobic bacteria in neonatal blood.

Term newborns at risk for early-onset neonatal sepsis: Clinical surveillance versus systematic paraclinical test.

INTRODUCTION: Early-onset neonatal sepsis is a rare but potentially lethal infection that is very often suspected in daily practice. Previous national guidelines recommended the use of systematic paraclinical tests for healthy term newborns with suspected infection. These guidelines were updated in 2017 by the French Health Authority (Haute Autorité de santé), and promote initial clinical monitoring taking into account the infectious risk level for term and near-term born infants. OBJECTIVES: To assess the impact of the new recommendations on antibiotic therapy prescription and invasive tests, and on the outcomes of infants born from 36weeks' gestation. MATERIALS AND METHODS: This study compared the management and the outcome of neonates born from 36weeks' gestation at the level III University Hospital of Nancy, according to their infectious risk level during two periods, before and after the update of national recommendations: from July 1 to December 31, 2017, versus July 1 to December 31, 2018. Data were retrospectively collected from the infants' files. This study compared the number and length of antibiotic treatment and the number of invasive tests, the number of documented infections, the number and length of hospitalization, and mortality between the two periods. RESULTS: During the first period, among 1248 eligible newborns, 643 presented an infectious risk factor, versus 1152 newborns with 343 having an infectious risk factor during the second period. Antibiotic treatment was initiated for 18 newborns during the first period (1.4%) and for nine during the second (0.8%) (P=0.13). The mean (SD) duration of the antibiotic treatment was longer in the first than in the second period: 6.3±2days vs. 3.1±2.3days (P=0.003). There was no death related to neonatal infection. A total of 1052 blood samples were collected during the first period versus 51 during the second (P<0.01). There was no documented infection. In the first period, there were 18 newborns (1.4%) hospitalized for suspected infection versus nine (0.8%) in the second period (P=0.13). The duration of hospitalization was 5.7±1.7days in the first period versus 5.2±3days in the second (P=0.33). CONCLUSION: In this study, the application of the new guidelines enabled a reduction of antibiotic exposure and a reduction of invasive tests without additional risk.

Targeting the eCIRP/TREM-1 interaction with a small molecule inhibitor improves cardiac dysfunction in neonatal sepsis.

BACKGROUND: Neonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective. METHODS: Serum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5-7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced by i.p. cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted. RESULTS: Serum eCIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival. CONCLUSIONS: Inhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis. Trial registration Retrospectively registered.

A Retrospective Review of Neonatal Sepsis among GBS-Colonized Women Undergoing Planned Cesarean Section after Labor Onset or Rupture of Membranes.

Background: Sepsis is a leading cause of mortality and morbidity in neonates, with group B streptococcus (GBS) remaining the most frequent pathogen isolated from term infants. Surveillance data showed that the majority of cases of early-onset GBS disease were neonates born to women who either received no or suboptimal intrapartum antibiotic prophylaxis with a notable portion of those women having a missed opportunity to receive ≥4 hours of chemoprophylaxis. Women planning delivery by cesarean section who present in labor or rupture of membranes prior to their scheduled surgery are unlikely to receive optimal GBS chemoprophylaxis and thus their neonates are at risk of having sepsis. Materials and Methods. A retrospective cohort study of women-infant dyads was extracted from the Consortium on Safe Labor dataset. Women who had an unlabored cesarean section at ≥37 + 0 week gestation were selected and divided into four groups based on GBS status and timing of cesarean section with respect to onset of labor or rupture of membranes. The rate of neonatal sepsis and the patterns of intrapartum antibiotic chemoprophylaxis were determined. Results: The sepsis rate (4.5%) among neonates of GBS-colonized women having their unlabored cesarean section after onset of labor or rupture of membranes was significantly higher than that in any other group in this study. In this group, 9.4% of women received chemoprophylaxis for ≥4 hours, while 31% had a missed opportunity to receive ≥4 hours of chemoprophylaxis. Conclusion: This study suggests that neonates of GBS-colonized women having a planned cesarean section after onset of labor or rupture of membranes are at increased risk of having a sepsis diagnosis. This finding suggest the need for additional studies to assess the risk of sepsis among neonates of women in this group.

The challenges of neonatal sepsis management / Os desafios no manejo da sepse neonatal

Abstract Objectives To present current evidence on the etiology, risk factors, diagnosis, and management of early and late neonatal sepsis. Source of data Non-systematic review of the Medline (PubMed), Scopus, Web of Science, Cochrane, and Google Scholar databases regarding the following terms: neonatal sepsis, early neonatal sepsis, late neonatal sepsis, empirical antibiotic therapy, sepsis calculator, vancomycin, newborn, preterm newborn. Data synthesis Neonatal sepsis is a frequent cause of neonatal morbidity and mortality. Its diagnosis is difficult. Continuous observation of the patient is critical to diagnostic suspicion. When neonatal sepsis is suspected, bacteriological tests should be collected. Vancomycin should not be routinely using in the empirical antibiotic regimen in late neonatal sepsis, and the main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk. Conclusions Newborns constitute a group that is more vulnerable to sepsis. Knowledge of risk factors and etiological agents allows a better approach to the newborn with sepsis.

Resumo Objetivos Apresentar evidências atuais na etiologia, fatores de risco, diagnóstico e manejo da sepse neonatal precoce e tardia. Fontes de dados Revisão não sistemática feita nas bases de dados Medline (PubMed), Scopus, Web of Science, Cochrane, Google Scholar sobre os temas sepse neonatal, sepse neonatal precoce, sepse neonatal tardia, antibioticoterapia empírica, sepsis calculator, vancomicina, recém-nascido, recém-nascido pré-termo. Síntese de dados A sepse neonatal é uma causa frequente de morbimortalidade neonatal. O seu diagnóstico é difícil. A observação contínua do paciente é fundamental para uma suspeição diagnóstica. Ao se suspeitar de sepse neonatal devem-se coletar exames bacteriológicos. Não usar, rotineiramente, vancomicina no esquema empírico de antibiótico na sepse neonatal tardia. Os principais mecanismos protetores da sepse neonatal são a lavagem de mãos e o uso do leite materno. Conclusões Os recém-nascidos constituem um grupo mais vulnerável à sepse. O conhecimento dos fatores de risco e dos agentes etiológicos permite uma melhor abordagem do recém-nascido séptico.

Leukocyte Counts and Other Hematological Values in Twin-Twin Transfusion Syndrome and Twin Anemia-Polycythemia Sequence.

OBJECTIVE: The aim of this study was to evaluate the differences in leukocyte counts at birth between donors and recipients with twin-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). METHODS: We performed a retrospective cohort study in monochorionic twin pairs with TTTS or TAPS. TTTS and TAPS cases treated with fetoscopic laser surgery were excluded. Primary outcome was the difference in leukocyte levels at birth between donor and recipient twins and the presence of leukopenia (defined as leukocyte count <4 × 109/L). Secondary outcomes included early-onset sepsis, necrotizing enterocolitis, use of antibiotics during admission, and neonatal mortality. RESULTS: We included 99 twins pairs, of which 61 twin pairs were affected by TAPS and 38 twin pairs by TTTS. The mean leukocyte count at birth in donors and recipients was 7.5 × 109/L versus 7.4 × 109/L (p = 0.936), respectively. Leukopenia was significantly more common in donor twins compared to recipient twins (7.1% [7/99] vs. 0% [0/99], p = 0.016). Of the 7 donors with leukopenia, 6 were affected by TAPS and 1 by TTTS. Overall, donors were more often affected by early-onset sepsis than recipients, 23.7% (23/97) versus 13% (13.7/95) (p = 0.049), respectively. CONCLUSIONS: Leukocyte counts at birth in twins with TTTS or TAPS are similar between donors and recipients, but TAPS donors are at an increased risk of leukopenia. Overall, TTTS and TAPS donors seem to be at an increased risk of early-onset neonatal sepsis compared to recipient twins.

Duodenal atresia with familial apple peel syndrome: case study with review of literature.

This is a case report of a neonate who was antenatally diagnosed with jejunal atresia which turned out to be duodenal atresia with apple peel syndrome. A previous sibling, who also had apple peel but with jejunal atresia, succumbed to sepsis after surgery. The first sibling had jejunal stenosis and had died of sepsis following surgery. Combination of duodenal atresia with apple peel is extremely rare. This coupled with a familial condition is rarer still. This case was challenging due to the short length of the gut and prolonged need for total parenteral nutrition and sepsis in postoperative period.

Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation. / Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación.

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.

Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación / Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation

INTRODUCCIÓN: Múltiples factores influyen en el riesgo de morbimortalidad del prematuro con restricción del crecimiento intrauterino (RCIU). La comparación de gemelos con crecimiento intrauterino discordante permite evaluar su efecto, excluyendo factores maternos y manejo prenatal. Nuestro objetivo fue evaluar el efecto de la RCIU sobre la morbilidad aguda, crónica y mortalidad, en parejas de recién nacidos gemelares prematuros extremos. PACIENTES Y MÉTODO: Gemelos menores de 1500 g y 30 semanas de gestación, de la Red Neocosur. Se realizaron análisis separados de pares de gemelos concordantes, discordantes leves y severos, evaluando el efecto de la RCIU sobre morbi-mortalidad. Se realizó análisis multivariado para establecer magnitud del efecto. RESULTADOS: 459 pares de gemelos, 227 concordantes, 110 discordantes leves y 122 severos. Entre los concordantes solo hubo diferencia en uso de oxígeno a las 36 semanas. En discordantes leves, el menor tuvo menos enfermedad de membrana hialina y requirió menos dosis de surfactante, pero tuvo un mayor riesgo de Displasia broncopulmonar (DBP) o muerte. En discordantes severos, el menor presentó mayor mortalidad, sepsis, utilización y permanencia en ventilación mecánica, pese a menor frecuencia de enfermedad de membrana hialina. En regresión múltiple, el riesgo combinado de DBP o muerte fue mayor en gemelo menor y discordante severo. CONCLUSIÓN: En gemelos discordantes, la patología respiratoria aguda fue más frecuente en el gemelo mayor, aunque el riesgo de DBP o muerte fue mayor en el gemelo con RCIU.

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.

A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants.

This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks' gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother's own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.

Detection of cytomegalovirus in saliva from infants undergoing sepsis evaluation in the neonatal intensive care unit: the VIRIoN-C study.

Objective To determine the frequency of detection of cytomegalovirus (CMV) among infants evaluated for late-onset sepsis in the neonatal intensive care unit (NICU). Methods This study was a prospective cohort study. Results During the 13-month study, 84 infants underwent 116 sepsis evaluations, and CMV DNA was detected in saliva in three (4%) infants (median: gestational age 28 weeks, birth weight 950 g), representing 5% (n=6) of all sepsis evaluations. One infant had CMV DNA detected in saliva in all four sepsis evaluations. Two infants had acquired CMV infection, while the timing of CMV acquisition could not be determined in one infant. Two of the three infants had concomitant Gram-negative bacteremia and urinary tract infections (UTIs), two developed severe bronchopulmonary dysplasia (BPD) and none died. Conclusion Detection of CMV DNA in saliva occurred in 4% of infants and 5% of sepsis evaluations. Persistence of CMV DNA shedding in saliva made attribution of clinical illness difficult to ascertain.

Deficiency of receptor-interacting protein kinase 3 (RIPK3) attenuates inflammation and organ injury in neonatal sepsis.

INTRODUCTION: Sepsis is the third leading cause of morbidity and mortality in neonates. Sepsis in neonates is characterized as the systemic inflammation owing to infection within the first 28days after birth. The molecular mechanism causing the exaggerated inflammation phenotype in neonates has not been completely elucidated. Receptor interacting protein kinase 3 (RIPK3) is a protein identified as a mediator in programmed necrosis or necroptosis. We hypothesize that RIPK3 could be responsible for the inflammatory response in neonates and that deficiency in the RIPK3 protein attenuates inflammation and organ injury in neonatal sepsis. METHODS: Male and female C57BL6 wild-type (WT) and RIPK3 knock-out (KO) newborn mice aged 5-7days (3-4g body weight) were injected intraperitoneally with 0.9mg/g cecal slurry (CS). At 10h after injection, the newborns were euthanized and blood, the lungs and gut tissues were collected. RESULTS: At 10h after CS injection, serum cytokines IL-6 and IL-1ß in the WT mice were increased by 511- and 43-fold whereas in KO mice, these levels were increased by 166-fold and 22-fold, respectively. Lung IL-1ß in the WT mice increased by 7-fold after CS injection whereas only a 4-fold increase was seen in the KO mice. In the lungs of CS injected KO mice, the injury score, MIP-2 mRNA, myeloperoxidase (MPO) activity and TUNEL staining were significantly reduced by 76%, 70%, 26% and 74%, respectively compared to the CS WT mice. Gut TUNEL staining was also reduced by 80%. CONCLUSION: The deficiency in RIPK3 attenuated serum and lung cytokines, lung injury and neutrophil infiltration and lung and gut apoptosis. These data suggest that RIPK3, in part, is responsible for the systemic inflammatory response in neonatal sepsis.

En mujeres embarazadas con rotura prematura de membranas y edad gestacional entre 34 y 37 semanas: ¿Es la interrupción del embarazo (manejo activo) mejor que el manejo expectante para reducir la sepsis neonatal? / In pregnant women with premature rupture of membranes and gestational age between 34 and 37 weeks: Is termination of pregnancy (active management) better than expectant management to reduce neonatal sepsis?

INTRODUCCIÓN: La rotura prematura de membranas (RPM) ocurre en un 8 a 10% de las embarazadas, y de ellas, un 20% corresponde a embarazos de pretérmino. El mayor riesgo para el feto luego de una RPM pretérmino son las complicaciones propias de la prematurez. Por debajo de las 34 semanas se favorece el manejo expectante, y el uso de antibióticos y corticoides. Entre las 34 y 37 semanas, sin embargo, las prácticas varían, no habiendo un consenso claro sobre la conducta óptima. OBJETIVO: El objetivo de esta revisión es explorar la evidencia actualmente disponible respecto de la conducta activa versus la expectante en embarazos con RPM entre las 34 y 37 semanas (36 semanas más 6 días). METODOLOGÍA: Se realizó una búsqueda de literatura médica en distintas bases de datos, dentro de las cuales se incluye "PubMed" y "Cochrane", usando los siguientes términos: "Fetal Membranes, Premature Rupture", "Premature Birth", "34 and 37 weeks" y "Clinical Trial". Se limitó la búsqueda a artículos que fueran ensayos clínicos aleatorizados. De un total de 31 trabajos, se seleccionaron 3, a los cuales se les aplicó la pauta de análisis crítico para evaluación de estudios de terapia. RESULTADOS: Se incluyeron 3 estudios que respondían a la pregunta planteada. En el primer estudio se concluyó que en pacientes en que hay interrupción inmediata la incidencia de sepsis neonatal es baja y no es posible demostrar que esta conducta mejore los resultados en comparación con el manejo expectante (2.6% vs. 4.1%). El manejo activo en este estudio se asoció a mayor incidencia de hiperbilirrubinemia, hipoglicemia, y mayor estadía hospitalaria neonatal. En el segundo artículo se planteó que la incidencia de sepsis neonatal sigue siendo baja, lo cual no disminuyó con la inducción del trabajo de parto. Esta tampoco disminuyó el riesgo de otros resultados neonatales o maternos. Finalmente, el tercer estudio concluyó que la interrupción inmediata aumenta las complicaciones neonatales sin disminución de la sepsis neonatal, pero a expensas de mayor frecuencia de fiebre materna y de hemorragia intraparto. CONCLUSIONES: El manejo expectante no es inferior al manejo activo en el contexto de RPM entre las semanas 34 a 37 de edad gestacional.

INTRODUCTION: Premature rupture of membranes (PROM) occur in eight to ten percent of pregnancies, and 20 percent of them occur in preterm pregnancies. Biggest fetal risks after preterm PROM are complications due to prematurity. Before 34 weeks of gestation it is preferred an expectant management, and the use of antibiotics and steroids. Between 34 and 37 weeks, however, practices are variable without a clear consensus about the best management. OBJECTIVE: The objective of this review is to explore the available evidence about active versus expectant management in pregnancies with PROM between 34 and 37 weeks (36 weeks plus 6 days). METHODS: Different databases were searched for medical literature, including 'PubMed' and 'Cochrane', using the following terms: 'Fetal Membranes, Premature Rupture', 'Premature Birth', '34 and 37 weeks' and 'Clinical Trial'. The search was limited to clinical randomized trials. From a total of 31 studies, three were selected, in which critical analysis guidelines for evaluation of therapy studies were applied. RESULTS: Three clinical trials which answered our question were included in this review. The first study concluded that in patients whose pregnancies were interrupted immediately, the incidence of neonatal sepsis was low but is was not able to demonstrate that this action improved outcomes compared to expectant management (2.6% vs 4.1%). Active management in this study was associated to greater incidences of hyperbilirubinemia, hypoglycemia and longer neonatal hospital stay. In the second article the incidence of neonatal sepsis was low and didn't decrease with induction of labor. It also didn't reduce the risk of other maternal nor neonatal outcomes. Finally, the third study concluded that induction of labor increased neonatal complications without reducing neonatal sepsis, but at the expense of increased frequency of intrapartum hemorrhage and maternal fever. CONCLUSION: After analyzing the selected articles, it is possible to conclude that there is enough evidence to say that expectant management is not inferior to active management in relation to PROM between 34 and 37 weeks of gestational age.

Neonatal sepsis.

Neonatal sepsis is the cause of substantial morbidity and mortality. Precise estimates of neonatal sepsis burden vary by setting. Differing estimates of disease burden have been reported from high-income countries compared with reports from low-income and middle-income countries. The clinical manifestations range from subclinical infection to severe manifestations of focal or systemic disease. The source of the pathogen might be attributed to an in-utero infection, acquisition from maternal flora, or postnatal acquisition from the hospital or community. The timing of exposure, inoculum size, immune status of the infant, and virulence of the causative agent influence the clinical expression of neonatal sepsis. Immunological immaturity of the neonate might result in an impaired response to infectious agents. This is especially evident in premature infants whose prolonged stays in hospital and need for invasive procedures place them at increased risk for hospital-acquired infections. Clinically, there is often little difference between sepsis that is caused by an identified pathogen and sepsis that is caused by an unknown pathogen. Culture-independent diagnostics, the use of sepsis prediction scores, judicious antimicrobial use, and the development of preventive measures including maternal vaccines are ongoing efforts designed to reduce the burden of neonatal sepsis.

Association between preterm brain injury and exposure to chorioamnionitis during fetal life.

Preterm infants are susceptible to inflammation-induced white matter injury but the exposures that lead to this are uncertain. Histologic chorioamnionitis (HCA) reflects intrauterine inflammation, can trigger a fetal inflammatory response, and is closely associated with premature birth. In a cohort of 90 preterm infants with detailed placental histology and neonatal brain magnetic resonance imaging (MRI) data at term equivalent age, we used Tract-based Spatial Statistics (TBSS) to perform voxel-wise statistical comparison of fractional anisotropy (FA) data and computational morphometry analysis to compute the volumes of whole brain, tissue compartments and cerebrospinal fluid, to test the hypothesis that HCA is an independent antenatal risk factor for preterm brain injury. Twenty-six (29%) infants had HCA and this was associated with decreased FA in the genu, cingulum cingulate gyri, centrum semiovale, inferior longitudinal fasciculi, limbs of the internal capsule, external capsule and cerebellum (p < 0.05, corrected), independent of degree of prematurity, bronchopulmonary dysplasia and postnatal sepsis. This suggests that diffuse white matter injury begins in utero for a significant proportion of preterm infants, which focuses attention on the development of methods for detecting fetuses and placentas at risk as a means of reducing preterm brain injury.