Short course of intravenous antibiotics in the treatment of uncomplicated proven neonatal bacterial sepsis: A systematic review.

AIM: To evaluate the efficacy and harms of a short (7-10 days) compared with a standard (10-14 days) duration of antibiotics in culture-proven neonatal sepsis for reducing all-cause mortality, treatment failure and duration of hospitalisation. METHODS: Medline, EMBASE and Cochrane CENTRAL were searched for randomised trials. RESULTS: We included five studies, all conducted in India (447 infants with a gestational age greater than 32 weeks). Except for one study, all studies were at high risk of bias. All-cause mortality was reported in three studies with only one death reported in the standard duration regimen arm (243 patients, very low certainty). A meta-analysis showed no evidence of the effect on treatment failure (RR of 1.47 [95% CI 0.48-4.50], 440 patients, five studies, very low certainty) of short-term antibiotics. Short-term antibiotic regimen shortened the duration of hospitalisation by 4 days (mean difference of -4.04 days [95% CI -5.47 to -2.61]; 4 studies; 371 patients; very low certainty). CONCLUSION: Among studies focused on infants born with a gestational age greater than 32 weeks, short-term administration of antibiotics may shorten the duration of hospitalisation, but the evidence is very uncertain. The evidence on other predefined outcomes is very uncertain to draw definite conclusions.

Early life nociceptive stimulus and fentanyl exposure increase hippocampal neurogenesis and anxiety but do not affect spatial learning and memory.

This study aimed to determine whether preemptive fentanyl administration in neonatal rats reduces the impact of a nociceptive stimulus initiated during the first day of life (P1) on hippocampal neurogenesis, behavior, and learning. At P1, Wistar rat pups received either a subcutaneous injection of fentanyl (F) before intraplantar injection of complete Freund's adjuvant (CFA) (CFA + F group), an isolated injection of CFA (CFA group), or subcutaneous injection of fentanyl without CFA injection (F). Control animals received saline injections using the same route and volume as the treatment groups. Hippocampal neurogenesis was evaluated by 5' -bromo-2'-deoxyuridine (BrdU) staining on P10 and P39 to assess neuronal proliferation and survival, respectively. Anxiety behavior in adulthood was assessed using an open field test (OF) and an elevated plus maze test (EPM). Spatial memory was assessed on a Morris water maze test (MWM), where the animals were trained for seven days, beginning on P81, and the probe trial was performed to evaluate memory retention. Although the CFA + F group showed an increased number of proliferative cells on P10, this finding did not persist on P39. The CFA + F group spent more time in the closed arms in the EPM, revealing more anxious behavior, although the early noxious experience, both with and without fentanyl, did not alter neurogenesis in adolescence and learning in adulthood. This study highlights that the impact of pain in early life pain combined with fentanyl on hippocampal neurogenesis on P10 did not persist on P39. In addition, this combined intervention during the first week of life was associated with higher anxiety levels.

Does neonatal manipulation on continuous or alternate days change maternal behavior?

Maternal separation and neonatal manipulation of pups produce changes in maternal behavior after the dam-pup reunion. Here, we examined whether continuous versus alternating days of neonatal manipulation during the first 8 postnatal days produces differential changes in maternal and non-maternal behaviors in rats. We found that both maternal separation protocols increased anogenital licking after dam-pup reunion, reflecting increased maternal care of pups.

Impact of bundle implementation on the incidence of peri/intraventricular hemorrhage among preterm infants: a pre-post interventional study.

BACKGROUND: Peri/intraventricular hemorrhage (PIVH) is a frequent cause of death and morbidity among preterm infants. Few studies have addressed the use of bundles for preventing PIVH. OBJECTIVE: To evaluate the efficacy of a bundle of interventions designed to decrease the incidence of intraventricular hemorrhage at hospital discharge among preterm infants. DESIGN AND SETTING: Pre-post interventional study with retrospective and prospective data collection performed before and after bundle implementation in the neonatal intensive care unit of a university hospital. METHODS: Infants with gestational age < 32 weeks without malformations, who survived > 6 days were included. The bundle consisted of the following actions during the first 72 hours of life: maintenance of head in neutral position with the body in supine position, minimal handling, including delay of lumbar puncture until after 72 hours and absence of respiratory therapy maneuvers. Cranial ultrasound was performed on days 3, 7 and 28, or later if needed. The effect of the bundle was analyzed through logistic regression and results were adjusted for confounding variables. RESULTS: 167 infants met the inclusion criteria; 146 (87%) were analyzed. Bundle implementation was associated with decreased chances of PIVH at hospital discharge (odds ratio 0.29; 95% confidence interval 0.13-0.65). Cerebrospinal fluid collection within the first 72 hours increased the odds of PIVH of any grade during the hospital stay fourfold, after adjustment for all variables included in the model. CONCLUSION: Implementation of a bundle of interventions to avoid intraventricular hemorrhage was effective for decreasing the incidence of all grades of PIVH in preterm infants.

Perinatal factors associated with amplitude-integrated electroencephalography abnormalities in preterm infants on the first day of life.

OBJECTIVE: Evaluate the association between perinatal factors and amplitude-integrated electroencephalogram abnormalities in preterm infants on the first day of life. METHODS: This was a cross-sectional study of 60 infants with gestational age between 23 and 32 weeks, without malformations. Infants were continuously monitored by amplitude-integrated electroencephalogram on the first day of life, for at least 3h. The tracings were recorded and analyzed in each column for the following: burst-suppression pattern, sleep-wake cycle, and amplitude of the lower margin (<3µV or <5µV). The association of maternal complications, mode of delivery, birth weight, gestational age, neonatal sex, resuscitation procedures, hypothermia on admission, and the Score for Neonatal Acute Physiology, Perinatal Extension, Version II [SNAPPE-II]) with amplitude-integrated electroencephalogram alterations was assessed by multiple logistic regression. RESULTS: A discontinuous pattern occurred in 65% of infants, and a continuous pattern occurred in 23%. The burst-suppression pattern was associated with vaginal delivery (OR: 7.6; 95% CI: 1.1-53.1) and SNAPPE-II≥40 (OR: 13.1; 95% CI: 1.8-95.1). A lower margin of the amplitude-integrated electroencephalogram of <3µV was also associated with SNAPPE-II≥40 (OR: 10.6, 95% CI: 2.3-49.2), while a value <5µV was associated with lower GA (OR: 0.51, 95% CI: 0.34-0.76). There were no associations between the perinatal variables and the absence of a sleep-wake cycle in amplitude-integrated electroencephalogram recordings on the first day of life. CONCLUSION: Biological variables and clinical severity are associated with electroencephalographic characteristics of preterm infants on the first day of life and should be considered in clinical practice when amplitude-integrated electroencephalogram is performed.

LPS-Induced Systemic Neonatal Inflammation: Blockage of P2X7R by BBG Decreases Mortality on Rat Pups and Oxidative Stress in Hippocampus of Adult Rats.

Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation has been associated to neuronal injury and facilitates the development of models of neurological disorders in adult rats. The P2X7 receptor (P2X7R) plays a fundamental role in the onset and maintenance of the inflammatory cascade. Brilliant blue G (BBG), a P2X7R antagonist, has been shown to effectively promote neuroinflammatory protection. Here, we have investigated the long-term effects of the neonatal systemic inflammation on hippocampal oxidative stress, anxiety behavior and pain sensitivity in adulthood. We hypothesized that P2X7R blockade is able to modulate the effects of inflammation on these variables. Male and female rat pups received LPS and/or BBG solution intraperitoneally on the 1st, 3rd, 5th and 7th postnatal days. The survival rate and body weight were evaluated during the experimental procedures. The animals were submitted to behavioral tests for anxiety (elevated plus maze, EPM) and nociception (hot-plate and tail-flick) and the oxidative stress was measured by superoxide production in the dentate gyrus of the hippocampus using dihydroethidium (DHE) probe. BBG increased the survival rate in LPS-treated rats. No significant differences were found regarding anxiety behavior and pain sensitivity between the experimental groups. Systemic neonatal inflammation leads to a higher production of superoxide anion in the dentate gyrus of the hippocampus in adulthood and BBG inhibited that effect. Our data suggest that blocking the activation of the P2X7R during neonatal systemic inflammation may have a potential neuroprotective effect in adulthood.

Neonatal procedural pain can be assessed by computer software that has good sensitivity and specificity to detect facial movements.

AIM: The difficulty in assessing pain during the neonatal period is one of the main obstacles for appropriate analgesia in intensive care units. The aim of this study was to develop and validate computer software to monitor neonatal facial movements of pain in real time. METHODS: The software was developed in the Delphi integrated development environment and provides real-time image analysis during monitoring, based on image recognition of pain-related facial actions. To validate the software performance, facial images were obtained during the monitoring of 30 neonates who were subjected to painful procedures related to daily care management. Of the 5644 images identified and analysed by the software, 360 images - 12 per infant - were randomly selected and assessed by six healthcare professionals with experience of recognising neonatal pain. RESULTS: The agreement between the examiners and the software assessment was excellent (κ = 0.975). The software exhibited 85% sensitivity and 100% specificity in detecting neutral facial expressions in the resting state and 100% sensitivity and specificity in detecting pain during painful procedures. CONCLUSION: It is possible to assess neonatal procedural pain using computer software that has good sensitivity and specificity to detect facial movements.

Assessment of fetal lung maturity by ultrasound: objective study using gray-scale histogram.

OBJECTIVE: To evaluate lung maturity using ultrasound (US), comparing the subjective and gray-scale histogram (GSH) techniques. METHODS: A total of 77 single pregnancies were evaluated and divided into the following two groups: 11 women of gestational age 28 to 35 + 6 weeks and 66 women ≥ 36 weeks. The women underwent to emergency or planned cesarean section, according to fetal-maternal indications. The US was performed on the mean sagittal plane of the fetal torso, in order to observe the lung and hepatic areas. Fetal lung maturity was evaluated subjectively and through GSH. After delivery, the incidence of respiratory distress in the newborn was evaluated. The analyses were considered to be correct or incorrect, and comparisons were made using the McNemar test. In order to compare lung/hepatic echogenicity using GSH in groups with and without respiratory distress, the Student's t-test was used. RESULTS: The subjective evaluation identified 41 cases (53.2%) correctly and 36 (46.8%) incorrectly, while GSH found 58 (75.3%) correctly and 19 (24.7%) incorrectly (p = 0.006). There was a significant difference in mean lung/hepatic echogenicity between the groups with and without respiratory distress (1.05 versus 1.26; p = 0.002). In the group of 28 to 35 + 6 weeks, GSH presented sensitivity, specificity and accuracy in predicting respiratory distress of 61.9%, 89.1% and 81.6%, respectively. CONCLUSION: The evaluation of fetal lung maturity through GSH was more effective than the subjective method in predicting respiratory distress among newborns.

Newborns with congenital heart diseases: epidemiological data from a single reference center in Brazil.

OBJECTIVE: to describe the epidemiological data of the population born with the diagnosis of Congenital Heart Disease (CHD); to compare diagnoses made using fetal echocardiography with the findings from postnatal echocardiography or anatomopathological examination of the heart; and to evaluate mortality among newborns that underwent surgical treatment. METHODS: this was a cohort study with information gathered from the medical records of the pregnant women and their newborns diagnosed with CHD during the fetal or postnatal periods, between January 2008 and December 2012. Means, standard deviations and maximum and minimum values were calculated for the quantitative variables. Relative and absolute values were calculated for the qualitative variables. The heart malformations were categorized in four groups: complex lesions, significant lesions, minor lesions and others. RESULTS: we detected postnatal incidence of CHD of 1.9% at our service. The mean maternal age was 28.3 years and 10 (21.3%) of the pregnant women were ≥ 35 years old. The mean gestational age at the time of performing the fetal echocardiogram was 27.8 weeks. Mean gestational age at delivery was 38 weeks, and the mean weight of the newborns was 2,644.5 grams. Regarding the diagnosis of CHD, there were: 23 complex lesions (39%); 15 significant lesions (26%); 10 minor lesions (17%); 4 other lesions (7%) and 6 normal anatomies (10%). The diagnosis of CHD made on the fetus and postnatally coincided in 77.6% of the cases. A total of 27 patients (60%) underwent surgery, and the outcome was neonatal death in five cases. CONCLUSION: we detected postnatal incidence of CHD of 1.9%, and it was more common among older pregnant women and with late detection in the intrauterine period. Complex heart diseases predominated, thus making it difficult to have a good result regarding neonatal mortality rates.

Prenatal detection of congenital heart diseases: one-year survey performing a screening protocol in a single reference center in Brazil.

Objective. To describe the experience of a tertiary center in Brazil to which patients are referred whose fetuses are at increased risk for congenital heart diseases (CHDs). Methods. This was a cross-sectional observational study. The data was collected prospectively, during the year 2012, through a screening protocol of the fetal heart adapted from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. We performed a fetal echocardiogram screening for all pregnant women who were referred to the fetal cardiology outpatient obstetrics clinic of a university hospital. The exams were classified as normal or abnormal. The cases considered abnormal were undergone to a postnatal echocardiogram. We categorized the abnormal fetal heart according to severity in "complex," "significant," "minor," and "others." Results. We performed 271 fetal heart screening. The incidence of abnormal screenings was 9.96% (27 fetuses). The structural CHD when categorized due to severity showed 48.1% (n = 13) of "complex" cases, 18.5% (n = 5) "significant" cases, and 7.4% (n = 2) "minor" cases. The most common referral reason was by maternal causes (67%) followed by fetal causes (33%). The main referral indication was maternal metabolic disease (30%), but there was just one fetus with CHD in such cases (1.2%). CHDs were found in 19/29 fetuses with suspicion of some cardiac abnormality by obstetrician (65.5%). Conclusion. We observed a high rate of CHD in our population. We also found that there was higher incidence of complex cases.