Functional immaturity in neonatal polymorphonuclear leukocytes of rhesus monkeys

Abstract: Despite major advances in the management and care of critically ill and low-birthweight human and nonhuman primate infants over the past two decades, infection remains a major source of neonatal morbidity and mortality. Although the causes of enhanced susceptibility and dissemination of neonatal infections are incompletely defined in the literature, substantial evidence from this and other laboratories has implied that functional abnormalities of neonatal polymorphonuclear leukocytes (PMNs) may be a major contributor. Increased understanding of the functional characteristics of neonatal PMNs should, therefore, provide significant insight into the pathogenesis and possible therapy of infections in neonates. Our laboratory has been actively involved in evaluating the functional competence of PMNs in neonatal human and nonhuman primates. This report describes a study in which we have confirmed and characterized the functional compromises in neonatal PMNs of rhesus monkeys, including deficiencies in chemotaxis, membrane deformability, phagocytosis, and killing.     

Psychosocial stress in pregnancy and its relation to the onset of premature labour.

A modified life events inventory was presented over a four-month period to 132 consecutive women going into spontaneous labour in Hull and Manchester. Three study groups were identified according to the duration of pregnancy. The levels of psychosocial stress in pregnancy were found to be particularly high in the mothers whose babies were born preterm. Stressful events may precipitate preterm labour in some women. The concept of antenatal care may have to be broadened if the incidence of premature labour and resulting perinatal mortality are to be reduced.     

THE OBSTETRICIAN'S RESPONSIBILITY IN INFANT MORTALITY

Although infant mortality has been remarkably reduced, stillbirth and neonatal death rates have been improved very little. Efforts at lowering the fetal death rate must be directed to those conditions affecting the fetus during labor or immediately afterward.Prevention of premature labor and better care of the premature infant during labor and the neonatal period offer hope of a greater salvage of premature infants. Proper environment and trained personnel are necessary.Spontaneous delivery is safest for the infant. Difficult operative procedures are associated with a high incidence of birth trauma, asphyxia and death.Since asphyxia is one of the chief causes of infant death, prevention, diagnosis and treatment of it are most important. Administration of oxygen to mildly asphyxiated infants before the injury has become irreversible may help to prevent late manifestations of anopia.     

Advances in prevention and therapy of neonatal dairy calf diarrhoea: a systematical review with emphasis on colostrum management and fluid therapy

Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy.     

Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study

Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery.Design Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health.Setting 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided dataParticipants 106 546 deliveries reported during the three month study period, with data available for 97 095 (91% coverage).Main outcome measures Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics.Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective.Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.     

Reduction of experimental necrotizing enterocolitis with anti-TNF-alpha

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. However, despite significant morbidity and mortality, the etiology and pathogenesis of NEC are poorly understood. Evidence suggests that ileal proinflammatory mediators such as IL-18 contribute to the pathology associated with this disease. In addition, we have previously shown that upregulation of TNF-alpha in the liver is correlated with ileal disease severity in a neonatal rat model of NEC. With the use of a neonatal rat model of NEC, we evaluated the incidence and severity of ileal damage along with the production of both hepatic and ileal proinflammatory cytokines in animals injected with (anti-TNF-alpha; n = 23) or without (NEC; n = 25) a monoclonal anti-TNF-alpha antibody. In addition, we assessed changes in apoptosis and ileal permeability in the NEC and anti-TNF-alpha groups. Ileal damage was significantly decreased, and the incidence of NEC was reduced from 80% to 17% in animals receiving anti-TNF-alpha. Hepatic TNF-alpha and hepatic and ileal IL-18 were significantly decreased in pups given anti-TNF-alpha compared with those sham injected. In addition, ileal luminal levels of both TNF-alpha and IL-18 were significantly decreased in the anti-TNF-alpha-injected group. Ileal paracellular permeability and the proapoptotic markers Bax and cleaved caspase-3 were significantly decreased in the anti-TNF-alpha group. These data show that hepatic TNF-alpha is an important component for the development of NEC in the neonatal rat model and suggest that anti-TNF-alpha could be used as a potential therapy for human NEC.     

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.     

Classification of perinatal mortality

A classification based upon pathophysiological mechanisms has been applied to perinatal mortality. The approximate relevance of each group was: fetal insufficiency 40%, respiratory failure 30%, developmental abnormality 20%, and the specific mechanisms 10%. Secondary subclassification of each category according to the maturity of the gestation emphasizes the importance of prematurity in the total perinatal mortality (66%) and the relevance of each pathophysiological mechanism in each phase of maturity. The principal mechanism in the mature group is fetal insufficiency and in the premature group, particularly between 20 and 28 weeks, it is neonatal respiratory failure. Perinatal death due to developmental abnormalities occurs most frequently in the mature infant and due to specific mechanisms in the premature infant, particularly between 29 and 36 weeks. It is suggested that greater emphasis should be placed on perinatal mortality rather than the separate consideration of stillbirth and neonatal mortality.     

Evaluation of newborn canine viability by means of umbilical vein lactate measurement, apgar score and uterine tocodynamometry

Newborn viability evaluation and early detection of fetal distress could contribute to reducing mortality at birth in canine species. High neonatal mortality rate in dogs is reported subsequent to complicated or uncomplicated whelping. Umbilical vein lactate and tocodynamometry could provide valuable clinical information to the obstetricians so that appropriate medical and surgical treatments or oxygen and warm administration can be properly and timely applied to mother and newborn pup. In humans, the fetal lactate level represents an objective indicator of fetal distress and a valid predictor of babies' survival. Fetal acidosis recognition by umbilical lactate (UL) measurement, APGAR score classification, and uterine activity monitoring during labour, can represent an advanced system in the evaluation of the canine newborn patient. The purpose of this study was to correlate UL levels with canine neonatal morbidity and mortality within 48 h of birth. We evaluated the relationship among neonatal parameters at birth (mucous membrane color, heart and respiratory rate, reflex irritability, mobility, suckling and vocalization, UL, weight, and temperature) with labour characteristics (uterine contractions recorded by the tocodynamometric system of Whelpwise™ Veterinary Perinatal Specialties®, delivery time, and pup presentation), in view to predict pup viability. We considered also vaginal parturition versus elective and emergency Caesarean section, and uterotonic drugs influence on delivery. Umbilical lactate concentration proved to be useful to predict canine neonatal mortality within 48 h of birth (P < 0.05). We identified 5 mmol/L of vein umbilical lactate concentration as the cut off value, allowing us to distinguish between healthy and distressed pups. Higher values of UL were related with distressed pups, whereas lower values characterized vigorous pups. Lactate concentrations lower than 5 mmol/L and APGAR scores higher than 9, related to mean delivery time of 105 min with effective uterine contractions (10 mm of Hg of strength or more, frequency from 4 to 12 contractions per hour, and 2-5 min in duration), should be considered good prognostic factors in canine labour and neonatology.     

Cardiac functional stress imaging: A sequential approach with stress echo and cardiovascular magnetic resonance

Background

An adequate placental perfusion is crucial for the normal growth and well being of the fetus and newborn. The blood flow through the placenta can be compromised in a variety of clinical situations, always causing important damage to the gestation. Our objective is to identify significant predictors for adverse neonatal outcome in severe fetal compromise.

Methods

Consecutive premature fetuses at between 25 and 32 weeks with severe placental insufficiency were examined prospectively. Inclusion criteria were: (i) singletons (ii) normal anatomy; (iii) abnormal umbilical artery Doppler pulsatility index (PI); (iv) abnormal cerebroplacental ratio; (v) middle cerebral artery (MCA) PI < - 2SD ("brain sparing"); (vi) last Doppler examination performed within 24 hours prior to delivery. All 46 patients that met criteria and started the study were followed to the end. We considered as independent potential predicting variables: absent or reversed end diastolic flow in umbilical artery, abnormal ductus venosus S/A ratio, absent or reversed flow during atrial contraction in the ductus venosus and birth weight Z score. Outcome parameters were: neonatal mortality and severe neonatal morbidity.

Results

Backward stepwise logistic regression analysis was used to determine the optimal model for the prediction of neonatal mortality and severe neonatal morbidity. In this analysis birth weight Z score index showed the strongest association OR = 1,87 [1,17-2,99] with all neonatal outcome, all other independent variables were excluded for the optimal model. There was no mortality for the group with normal birth weight Z score.

Conclusion

Our study suggests that birth weight Z score is the strongest predictor of adverse neonatal outcome in severe placental insufficiencies. Such use of Z scores, allowing to get rid of gestational age or sex covariates could be extended to estimated fetal weight and might help in making important decisions in the management of compromised pregnancies.     

Contribution of preterm delivery to perinatal mortality.

A detailed retrospective analysis was made of the records of 486 preterm infants, who accounted for 5-1% of all births during 1973 and 1974. Whereas preterm delivery did not contribute to perinatal mortality in terms of stillbirth, it outweighed all other causes in terms of early neonatal deaths. Preterm birth was responsible for 85% of the early neonatal deaths not due to lethal congenital deformities. Early neonatal mortality rates were closely linked both to gestational age and birth weight and to the reason for preterm birth. Early neonatal mortality was high (97 per 1000) when preterm labour was spontaneous, whether or not associated with material or fetal disease or with multiple pregnancy, but low (27 per 1000) when preterm delivery was elective. Preventing spontaneous preterm labour would considerably reduce neonatal mortality in our community.     

Recommendations for ensuring early thrombolytic therapy for acute myocardial infarction. The Heart and Stroke Foundation of Canada,the Canadian Cardiovascular Society and the Canadian Association of Emergency Physicians for the Emergency Cardiac Care Coalition.

OBJECTIVE: To recommend practical steps to ensure early thrombolytic therapy and thereby reduce mortality and morbidity associated with acute myocardial infarction (AMI). OPTIONS: Various factors were considered that influence time to thrombolysis related to patients, independent practitioners and health care systems. OUTCOMES: Reduction in morbidity and mortality associated with AMI. EVIDENCE: Early initiation of thrombolytic therapy reduces morbidity and mortality associated with AMI. The ECC Coalition analysed the factors that might impede early implementation of thrombolytic therapy. VALUES: Published data were reviewed, and recommendations were based on consensus opinion of the Emergency Cardiac Care (ECC) Coalition. The ECC Coalition comprises 20 professional, nongovernment and government organizations and has a mandate to improve emergency cardiac care services through collaboration. BENEFITS, HARMS AND COSTS: Early thrombolytic therapy reduces morbidity and mortality associated with AMI. Implementation of the recommendations will result in reduced time to thrombolytic therapy, streamlining of current practices and enhanced cooperation among health care professionals to expedite care. Depending on existing practices, implementation may require protocol development, and public and professional education. Although costs are associated with educating the public and health care professionals, they are outweighed by the financial and social benefits of reduced morbidity and mortality. RECOMMENDATIONS: Early recognition of AMI symptoms by the public and health care professionals, early access to the emergency medical services system and early action by emergency care providers in administering thrombolytic therapy (within 30 minutes after the patient''s arrival at the emergency department). VALIDATION: No similar consensus statements or practice guidelines for thrombolytic therapy in Canada are available for comparison.     

胎膜早破后羊水残余量与宫内感染和新生儿发病率的相关性分析

目的：探讨胎膜早破后残余羊水量与宫内感染和新生儿发病率的相关性。方法：根据产妇胎膜早破后残余羊水指数（Amnitic Fluid Index,AFI）的监测结果,将本组120例产妇分为三组：羊水量正常组82例;羊水量较少组20例;羊水量过少组18例。所有产妇入院后行胎膜早破常规处理,回顾分析并统计三组产妇宫内感染率,胎儿窘迫率和新生儿发病率。结果：在宫内感染发生率上,三组比较,差异具有显著性,羊水量较少组、羊水量过少组宫内感染的发生率明显高于羊水量正常组（P〈0．01）。在胎儿窘迫发生率上,三组比较,差异无统计学意义（P〉0．05）。在新生儿发病率上,三组比较,差异具有显著性,羊水量较少组、羊水量过少组新生儿的发病率明显高于正常纽（P〈0．01）。Logistic回归分析发现羊水量、产妇基础性疾病和分娩孕周为孕产妇宫内感染和新生儿发病的关键影响因素。结论：胎膜早破后残余羊水量过少与宫内感染和新生儿发病=翠的升高密切相关,产妇于胎膜早破后应加强残余羊水量的监测,以采取有效措施降低宫内感染和新生儿发病的发生率。     

The epidemiology of preterm birth

Preterm birth is a major clinical problem, accounting for 47% of all neonatal deaths. The preterm delivery rate in UK is approximately 7%, and rates of preterm birth are steadily increasing. The diagnosis of preterm labour is difficult and most interventions to halt labour are unsuccessful. Despite this, the lack of good data hinders high quality research. The West Midlands has the highest perinatal mortality in the UK and a Perinatal Institute was set up in 2000 to address this, and aid improvements in care. Survival rates amongst preterm infants have changed dramatically over the last decade, with 88% survival for 2728 weeks, and 21% for > or =24 weeks (depending on birth weight). Risk factors include lower social class, less education, single marital status, low income, younger maternal age, low body weight, ethnicity, smoking, poor housing along with medical factors such as induction, premature rupture of membranes, infection, multiple pregnancy intrauterine death, fetal and uterine abnormalities and chorioamnionitis. Data from further detailed, robust studies are required to facilitate a comprehensive understanding of risk factors and their relationship with each other. Only then will it be possible to influence the adverse outcomes described.     

Recent Studies on Invasive Fungal Diseases in Children and Adolescents: an Update

The improved survival of fragile pediatric hosts such as those afflicted with primary or acquired immune deficiencies, prematurity, and surgical pathology – mainly gastrointestinal and trauma – has resulted in an increased number of children susceptible to invasive fungal infections. These infections are associated with significant morbidity and mortality. Newer, safer antifungal agents allow for preventive and empiric strategies in the management of patients at risk, such as premature infants, patients receiving chemotherapy, and bone marrow or solid-organ transplant recipients. Improved radiological and molecular techniques result in earlier diagnosis of fungal infections, allowing for preemptive therapy in these patients, minimizing exposure to antifungal agents and the risk of emergence of resistant fungal strains. A better understanding of the differences in pharmacokinetics between children and adults will allow for better utilization of existing antifungal agents and improved outcomes.     

Labour: when to worry.

To ensure an optimum result in pregnancy it is essential that the physician be alert in the antenatal period to recognize those women and their babies who are at risk during labour. Premature labour, with its attendant risk of respiratory distress syndrome in the newborn, continues to be an important factor in perinatal morbidity and mortality. Early recognition of predisposing factors and the judicious use of myometrial inhibiting agents have helped to reduce the incidence of fetal prematurity in these cases. A long interval between rupture of the membranes and delivery continues to be a danger to both mother and fetus. Delivery is recommended when gestation is beyond 36 weeks or when there are signs of incipient infection, and once labour has begun antibiotics should be used prophylactically. Failure of labour to progress should be recognized and managed aggressively in its early stages. Amniotomy and oxytocin infusion have reduced considerably the incidence of prolonged labour and its risks to both mother and fetus. The role of intrapartum monitoring of the fetal heart rate, measurement of the pH in the fetus''s scalp blood and assessment of amniotic fluid is discussed, as is the monitoring of maternal well-being.     

Intracranial aneurysms: analysis of results of microneurosurgery.

Subarachnoid haemorrhage from intracranial aneurysms has a poor prognosis. Operative management of intracranial aneurysms was once considered ineffective. The first 100 cases treated by micorsurgery were analysed to see whether mortality and morbidity were reduced. Modern surgical techniques halved the total mortality but the morbidity was unaltered. Results can be improved by delaying surgery seven days and by treating any hypertension before surgery.     

A Computational Model of Lipopolysaccharide-Induced Nuclear Factor Kappa B Activation: A Key Signalling Pathway in Infection-Induced Preterm Labour

Preterm birth is the single biggest cause of significant neonatal morbidity and mortality, and the incidence is rising. Development of new therapies to treat and prevent preterm labour is seriously hampered by incomplete understanding of the molecular mechanisms that initiate labour at term and preterm. Computational modelling provides a new opportunity to improve this understanding. It is a useful tool in (i) identifying gaps in knowledge and informing future research, and (ii) providing the basis for an in silico model of parturition in which novel drugs to prevent or treat preterm labour can be “tested”. Despite their merits, computational models are rarely used to study the molecular events initiating labour. Here, we present the first attempt to generate a dynamic kinetic model that has relevance to the molecular mechanisms of preterm labour. Using published data, we model an important candidate signalling pathway in infection-induced preterm labour: that of lipopolysaccharide (LPS) -induced activation of Nuclear Factor kappa B. This is the first model of this pathway to explicitly include molecular interactions upstream of Nuclear Factor kappa B activation. We produced a formalised graphical depiction of the pathway and built a kinetic model based on ordinary differential equations. The kinetic model accurately reproduced published in vitro time course plots of Lipopolysaccharide-induced Nuclear Factor kappa B activation in mouse embryo fibroblasts. In this preliminary work we have provided proof of concept that it is possible to build computational models of signalling pathways that are relevant to the regulation of labour, and suggest that models that are validated with wet-lab experiments have the potential to greatly benefit the field.     

Is There Still a Place for Conventional Amphotericin B in the Treatment of Neonatal Fungal Infections?

Neonatal invasive fungal infections (IFIs) remain an increasing problem associated with high rates of morbidity and mortality, as well as late-onset neurodevelopmental implications. Invasive candidiasis remains the leading neonatal IFI. Candida albicans is the fungal species most often affecting this population, although a changing epidemiologic incidence to non-albicans Candida species is reported in some neonatal intensive care units. Many treatment recommendations are extrapolated from adult populations, emphasizing the need to establish the optimal antifungal agent, dosage, and duration of therapy in neonates. Historically, conventional amphotericin B has been considered an efficient and safe treatment approach for most neonatal IFIs. More recently, lipid formulations of amphotericin B have been studied, used alone or in combination with other antifungal agents such as azoles or echinocandins. The aim of this article is to review the published experience in the use of amphotericin B formulations to treat neonatal IFIs.     

Spontaneous preterm labour and delivery at under 34 weeks' gestation.

The management and outcome of 242 infants delivered between 26 and 34 weeks'' gestation in an obstetrical and neonatal regional referral centre as a result of spontaneous preterm labour were recorded prospectively. Results of the survey show that the decision to intervene and delay delivery will depend on the availability of neonatal intensive care facilities. Infants likely to require intensive neonatal care should be transferred in utero to a centre with these facilities. The use of steroids reduces the mortality of preterm infants. The maximum effect occurs between 30 and 32 weeks'' gestation, and there is no benefit after 34 weeks. If the weight is over 1500 g the mode of delivery of the preterm infant presenting by the breech does not influence outcome; if under 1500 g a caesarean section improves survival over those infants born by vaginal breech delivery.