Neonatal Day Research Articles

Prenatal Alcohol Exposure Causes Adverse Cardiac Extracellular Matrix Changes and Dysfunction in Neonatal Mice.

Fetal alcohol syndrome (FAS) is the most severe condition of fetal alcohol spectrum disorders (FASD) and is associated with congenital heart defects. However, more subtle defects such as ventricular wall thinning and cardiac compliance may be overlooked in FASD. Our studies focus on the role of cardiac fibroblasts in the neonatal heart, and how they are affected by prenatal alcohol exposure (PAE). We hypothesize that PAE affects fibroblast function contributing to dysregulated collagen synthesis, which leads to cardiac dysfunction. To investigate these effects, pregnant C57/BL6 mice were intraperitoneally injected with 2.9g EtOH/kg dose to achieve a blood alcohol content of approximately 0.35 on gestation days 6.75 and 7.25. Pups were sacrificed on neonatal day 5 following echocardiography measurements of left ventricular (LV) chamber dimension and function. Hearts were used for primary cardiac fibroblast isolation or protein expression analysis. PAE animals had thinner ventricular walls than saline exposed animals, which was associated with increased LV wall stress and decreased ejection fraction. In isolated fibroblasts, PAE decreased collagen I/III ratio and increased gene expression of profibrotic markers, including α-smooth muscle actin and lysyl oxidase. Notch1 signaling was assessed as a possible mechanism for fibroblast activation, and indicated that gene expression of Notch1 receptor and downstream Hey1 transcription factor were increased. Cardiac tissue analysis revealed decreased collagen I/III ratio and increased protein expression of α-smooth muscle actin and lysyl oxidase. However, Notch1 signaling components decreased in whole heart tissue. Our study demonstrates that PAE caused adverse changes in the cardiac collagen profile and a decline in cardiac function in the neonatal heart.

Lack of Variability in Cerebral Oximetry Tendency in Infants with Severe Hypoxic-Ischemic Encephalopathy Under Hypothermia.

Cerebral oximetry using near-infrared spectroscopy (NIRS) provides continuous, noninvasive assessment of the degree of hemoglobin saturation of the brain tissue. Previous studies suggest that high values of regional cerebral tissue oxygen saturation (rScO2) during the first days in neonates with significant hypoxic-ischemic encephalopathy (HIE) are correlated with an adverse neurological outcome. However, the results are not consistent among the studies. To examine the correlation of rScO2 values and their variability over time with HIE severity, amplitude integrated electroencephalography (aEEG) background and seizure activity, neuron-specific enolase levels in cerebrospinal fluid, magnetic resonance imaging (MRI) findings, and neurological outcome. Retrospective study that included all consecutive infants with moderate-to-severe HIE born at ≥35 weeks gestational age admitted between January 2011 and December 2014. NIRS monitoring was initiated at admission and maintained during therapeutic hypothermia up to 12 hours after rewarming. To analyze rScO2, different periods (0-6, 6-24, 24-48, 48-72, and 72-100 hours of life) and three ranges (<55%, 55-90%, >90%) were considered. Variability in each patient was considered ≤5% when changes in rScO2 values in all periods were ≤5%. Twenty-three newborns were included. Infants who suffered from severe HIE, seizures, abnormal aEEG background, altered MRI or death, and abnormal outcome had rScO2 values >90% and with less variability (≤5%). rScO2 values >90% and a lack of variability over time in infants with HIE during cooling provide useful information about the severity of neurological status.

Statistical Modeling for Findings the Determinants of Neonates’ Very Low Birth Weight

Aim of the epidemiological research is to identify a causal relationship between the risk factors and the disease. The present study aims to identify the determinates of neonates’ very low birth weight which have significant effects on their birth weight using generalized additive probabilistic modeling. In this present study very low birth weight (BWT) is the response variable with heterogeneity and non-normality in nature which can be modeled through either by the Log-normal or by the gamma models. A well-known method is joint modeling of mean and variance (JGLM) to handle this heterogeneity and non-normality but this study introduced the most advanced regression techniques namely generalized additive model (GAM). Materials and Methods: The present article is based on the secondary data on 174 very low birth weighted neonates along with 26 explanatory factors/ variables. The very low birth weight of 174 neonates is heterogeneous, positive, and gamma distributed. Therefore, generalized additive model with gamma distribution and log link function has been introduced to analyze this very low birth weight. The Native American neonates has the smaller birth weight (BWT) than the other racial neonates namely black, white or oriental (P-value = 0.009). The BWT is smaller for those neonates who were outsiders from Duke (P-value = 0.05) and it also decreases to the female births (P- value=0.09). BWT is higher for the pneumothorax infants than non-pneumothorax with P-value <0.001. It is smaller for those infants for whom oxygen supply had been introduced in between 30 days of his/her birth (P-value=0.002). The neonates who were not been survived they also have the smaller birth weight than the alive neonates (P-value= 0.07). Besides these factors, lowest pH in first 4 days of neonates’ life (P-value=0.09), Apgar score at one minute (P-value=0.03) and the interaction effects of lowest pH and Apgar score (0.03) are the significant variables (continuous cofactors) for neonates’ very low birth weight. Hospital stays in number of days, platelet counts and gestational age in weeks are also highly significant factors and these are entered in the GAM model as a non –parametric smoothing term (P-value<0.001). The birth weight of each new born baby is identified as heterogeneous and gamma distributed (possible). Most of the present findings, especially the Apgar score in one minute, occurrence of pneumothorax in neonates, oxygen supply given to new born baby within 30 days of life and smoothing term determinants namely number of days hospital stay, platelet counts and gestational age in weeks (non-parametric smoothing terms) are significant factors for neonate’s birth weight and are completely new in the literature.

Predictive Role of Urinary Metabolic Profile for Abnormal MRI Score in Preterm Neonates.

Background and Objective Early identification of neonates at risk for brain injury is important to start appropriate intervention. Urinary metabolomics is a source of potential, noninvasive biomarkers of brain disease. We studied the urinary metabolic profile at 2 and 10 days in preterm neonates with normal/mild and moderate/severe MRI abnormalities at term equivalent age. Methods Urine samples were collected at two and 10 days after birth in 30 extremely preterm infants and analyzed using proton magnetic resonance spectroscopy. A 3 T MRI was performed at term equivalent age, and images were scored for white matter (WM), cortical grey matter (cGM), deep GM, and cerebellar abnormalities. Infants were divided in two groups: normal/mild and moderately/severely abnormal MRI scores. Results No significant clustering was seen between normal/mild and moderate/severe MRI scores for all regions at both time points. The ROC curves distinguished neonates at 2 and 10 days who later developed a markedly less mature cGM score from the others (2 d: area under the curve (AUC) = 0.72, specificity (SP) = 65%, sensitivity (SE) = 75% and 10 d: AUC = 0.80, SP = 78%, SE = 80%) and a moderately to severely abnormal WM score (2 d: AUC = 0.71, specificity (SP) = 80%, sensitivity (SE) = 72% and 10 d: AUC = 0.69, SP = 64%, SE = 89%). Conclusions Early urinary spectra of preterm infants were able to discriminate metabolic profiles in patients with moderately/severely abnormal cGM and WM scores at term equivalent age. Urine spectra are promising for early identification of neonates at risk of brain damage and allow understanding of the pathogenesis of altered brain development.

275. Maternal, fetal and neonatal outcomes of women diagnosed with preeclampsia according to the new ISSHP and ACOG criteria

Introduction Preeclampsia is characterized by new-onset of hypertension and proteinuria after 20 weeks of gestation. The inaccuracies in the measurement of proteinuria combined with the occurrence of complications in women with de novo hypertension without proteinuria led both the ACOG and ISSHP to revise their definition of preeclampsia. Objective To determine the difference in maternal, fetal and neonatal outcomes in women diagnosed with preeclampsia according to the traditional ISSHP 2001 criteria and the new ISSHP 2014 and ACOG 2013 criteria.Methods In a cohort of 616 women with hypertensive pregnancy disorders admitted between 2014 and 2016, we determined the maternal, fetal and neonatal outcomes according to the different criteria. Results The number of maternal and of fetal/neonatal complications was respectively 127 (21%) and 237 (38%). Median (range) gestational age at time of delivery was 35 (20–41) weeks according to all three criteria. On grounds of the traditional criteria (ISSHP 2001), median (range) birth weight was 2168 (280–4640) and declined to 2107 (170 – 4640) for ISSHP 2014 and 2125 (280–4640) for ACOG 2013 (p > 0.05). No differences were found in maternal complication rate between the 3 groups. The number of patients with intrauterine growth restriction increased by 16 (80%) (ISSHP 2014) and 5 (25%) (ACOG 2013). Finally, no differences were observed in other fetal or neonatal complications and hospitalization days. Conclusion Overall, no differences in maternal, fetal or neonatal outcomes were observed in women diagnosed with preeclampsia according to the new criteria (ISSHP 2014 and ACOG 2013). As the presence of intrauterine growth restriction, in contrast to the diagnosis of preeclampsia, does not necessarily require admission, an important question remains whether to include this in the diagnosis of preeclampsia. Prospective trials are warranted to assess whether application of the new criteria will significantly improve clinical outcomes.

Neonatal Ventilator Associated Pneumonia: A Quality Improvement Initiative Focusing on Antimicrobial Stewardship.

Background and Aims: Neonatal ventilator associated pneumonia (VAP) is a common nosocomial infection and a frequent reason for empirical antibiotic therapy in NICUs. Nonetheless, there is no international consensus regarding diagnostic criteria and management. In a first step, we analyzed the used diagnostic criteria, risk factors and therapeutic management of neonatal VAP by a literature review. In a second step, we aimed to compare suspected vs. confirmed neonatal VAP episodes in our unit according to different published criteria and to analyze interrater-reliability of chest x-rays. Additionally, we aimed to evaluate the development of VAP incidence and antibiotic use after implementation of multifaceted quality improvement changes regarding antimicrobial stewardship and infection control (VAP-prevention-bundle, early-extubation policy, antimicrobial stewardship rounds).Methods: Neonates until 44 weeks of gestation with suspected VAP, hospitalized at our level-III NICU in Lucerne from September 2014 to December 2017 were enrolled. VAP episodes were analyzed according to 4 diagnostic frameworks. Agreement regarding chest x-ray interpretation done by 10 senior physicians was assessed. Annual incidence of suspected and confirmed neonatal VAP episodes and antibiotic days were calculated and compared for the years 2015, 2016, and 2017.Results: 17 studies were identified in our literature review. Overall, CDC-guidelines or similar criteria, requesting radiographic changes as main criteria, are mostly used. Comparison of suspected vs. confirmed neonatal VAP episodes showed a great variance (20.4 vs. 4.5/1,000 ventilator-days). The interrater-reliability of x-ray interpretation was poor (intra-class correlation 0.25). Implemented changes resulted in a gradual decline in annual VAP incidence and antibiotic days from 2015 compared with 2017 (28.8 vs. 7.4 suspected episodes/1,000 ventilator-days, 5.5 vs. 0 confirmed episodes/1,000 ventilator-days and 211 vs. 34.7 antibiotic days/1,000 ventilation-days, respectively).Conclusion: The incidence of suspected VAP and concomitant antibiotic use is much higher than for confirmed VAP, therefore inclusion of suspected episodes should be considered for accurate evaluation. There is a high diagnostic inconsistency and a low reliability of interpretation of chest x-rays regarding VAP. Implementation of combined antimicrobial stewardship and infection control measures may lead to an effective decrease in VAP incidence and antibiotic use.

Blood Procalcitonin Levels and Duration of Antibiotics in Neonatal Sepsis.

To determine the time to normalization of procalcitonin (PCT) levels and duration of antibiotics in neonatal sepsis. A prospective observational study design was used. The participants included were neonates with sepsis. The primary outcome measure was time to normalization of PCT levels and duration of antibiotics following clinical resolution. Time to normalization of PCT levels was 9.6 ± 4.2 days in neonates with septic shock, 6.2 ± 2.5 days in neonates without shock, 9.6 ± 3.1 days in neonates with culture-positive sepsis and 6.4 ± 3.1 days in neonates with culture-negative sepsis. Time to normalization of PCT levels according to the stage of systemic inflammatory response syndrome was 5.8 ± 2.8 days in neonates with sepsis, 6.1 ± 3.1 days in those with sepsis syndrome, 6.3 ± 3.3 days in those with early septic shock and 9.4 ± 3.6 days in those with multiorgan dysfunction syndrome. There was no morbidity and mortality in any neonate in the 4-week follow-up. The duration of antibiotics can be determined by observing the time to normalization of PCT following clinical resolution of sepsis.

Abstract 405: Antioxidant Treatment Prevents Profibrotic Changes And Cardiac Dysfunction In Prenatal Alcohol Exposure

Prenatal ethanol exposure is often associated with cardiac defects. Our studies focus on the role of cardiac fibroblasts in the developing heart, and how they are affected by prenatal ethanol exposure. There have been numerous studies demonstrating the protective effects of antioxidant treatment against alcohol-induced injury during cardiac development. Thus, we hypothesize that in utero ethanol (EtOH) exposure creates oxidative stress and activates neonatal cardiac fibroblasts, leading to a profibrotic phenotype and cardiac dysfunction. Further, we hypothesize that these effects are prevented by antioxidant treatment. We performed in utero EtOH administration to C57/BL6 mice on gestation days 6.75 and 7.5. Dams were intraperitoneally injected with 2.9 g EtOH/kg body weight to produce a blood EtOH content of ~0.26 g/dL each time. Controls were injected with vehicle saline. Randomly selected dams in both groups were treated with 100 gram/kg body weight of the antioxidant N-acetylcysteine (NAC) immediately after EtOH or vehicle administration. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Eccentric index was calculated as a ratio of LV interior diameter and LV posterior wall thickness*2 at diastole. Eccentric index increased in EtOH-exposed animals (2.2±0.1 EtOH vs 1.8±0.1 saline, p&lt;0.05). There were no changes in EtOH animals treated with NAC (1.9±0.1, NS). Additionally, ejection fraction decreased in the EtOH group (60±2% EtOH vs 68±2% saline). NAC treatment prevented this depression of systolic function in EtOH-exposed neonates (72±2%). Hearts were analyzed for expression of profibrotic proteins. In EtOH-exposed pups, collagen I decreased (0.02±.01 vs 0.04±.01 au), but collagen III expression increased (0.21±.02 vs 0.13±.01 au) compared to saline animals; the overall collagen I/III ratio significantly decreased (0.47±0.07 vs 1.0±0.17). When EtOH-exposed mice were treated with NAC, collagen I/III ratio did not change (0.83±0.11). Overall, our data demonstrate that in utero EtOH exposure produces a profibrotic phenotype in neonatal hearts and a decline in both diastolic and systolic function. These adverse effects were prevented by antioxidant treatment.

Neonatal Neurodegeneration in Alzheimer's Disease Transgenic Mouse Model.

Alzheimer’s disease (AD) is a progressive disorder characterized by a variety of molecular pathologies causing cortical dementia with a prominent memory deficit. Formation of the pathology, which begins decades before the diagnosis of the disease, is highly correlated with the clinical symptoms. Several proteomics studies were performed using animal models to monitor the alterations of the brain tissue proteome at different stages of AD. However, proteome changes in the brain regions of newborn transgenic mouse model have not been investigated yet. To this end, we analyzed protein expression alterations in cortex, hippocampus and cerebellum of transgenic mice carrying five familial AD mutations (5XFAD) at neonatal day-1. Our results indicate a remarkable difference in protein expression profile of newborn 5XFAD brain with region specific variations. Additionally, the proteins, which show similar expression alteration pattern in postmortem human AD brains, were determined. Bioinformatics analysis showed that the molecular alterations were mostly related to the cell morphology, cellular assembly and organization, and neuroinflammation. Moreover, morphological analysis revealed that there is an increase in neurite number of 5XFAD mouse neurons in vitro. We suggest that, molecular alterations in the AD brain exist even at birth, and perhaps the disease is silenced until older ages when the brain becomes vulnerable.

In utero alcohol exposure alters the collagen profile in neonatal hearts and leads to cardiac dysfunction

Fetal alcohol syndrome is often associated with congenital heart defects. Our studies focus on the role of cardiac fibroblasts in the developing heart, and how they are affected by prenatal ethanol exposure. Fibroblasts are the most numerous cardiac cell type and play an essential role in development of the heart. They are responsible for synthesis of the extracellular matrix, which provides the scaffold for heart muscle. Our lab has previously shown that ethanol exposure in adult hearts promote fibroblast activation and transition into myofibroblasts. Based on this, we believe that in utero ethanol exposure causes alterations in fibroblast function that could contribute to dysregulation in collagen synthesis and impaired scaffolding of the neonatal heart. Therefore, we hypothesize that in utero ethanol activates neonatal cardiac fibroblasts, which leads to a profibrotic phenotype and cardiac dysfunction.To investigate these effects, we performed in utero EtOH administration in wildtype dams. Pregnant mice were intraperitoneally injected with 2.9 g EtOH/kg body weight to achieve a blood ethanol content of approximately 0.26 on gestation day 6.75. On neonatal day 5, pups were weighed prior to sacrifice. Body weight was decreased in the WT+EtOH pups, which is a hallmark of fetal alcohol syndrome. Hearts were homogenized, and Western Blot analysis was performed to determine protein expression. Collagen I decreased in ethanol exposed neonates, but collagen III expression was significantly increased, so the collagen I/III ratio was decreased. Collagen I gives hearts a more tensile and stiff phenotype, whereas collagen III gives a more compliant phenotype; therefore, a decrease in collagen I/III ratio would correlate with a dilated heart. Subsequently, this can significantly impair diastolic function. Overall, our data shows a correlation between prenatal ethanol exposure and a profibrotic phenotype in neonatal hearts.We were further interested in assessing whether these changes in collagen translated into changes in cardiac function. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Eccentric index was calculated as a ratio of LV interior diameter and LV posterior wall thickness*2 at diastole and at systole. There was a significant increase in the eccentric index at both systole and diastole in ethanol exposed animals, indicative of LV dilation. This is in agreement with our previous collagen findings, which further supports the possibility of a dilated cardiac phenotype. In analyzing systolic function, LV end systolic volume increased, and both ejection fraction and fractional shortening decreased in the ethanol treated animals. Our functional measurements demonstrate that in utero ethanol exposure decreases collagen I/III protein ratio in neonatal hearts, which ultimately causes a decline in both diastolic and systolic function.Support or Funding InformationSaving Tiny Hearts SocietyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cost-effectiveness of digoxin, pacing, and direct current cardioversion for conversion of atrial flutter in neonates.

The cost analysis for cardioversion of atrial flutter found the most efficient method to be direct current cardioversion at a cost of $10 304, pacing was next at $11 086, and the least cost-effective was digoxin at $14 374. The majority of additional cost, regardless of method, was from additional neonatal ICU day either owing to digoxin loading or failure to covert. Direct current cardioversion remains the most cost-effective strategy by sensitivity analyses performed on pacing conversion rate and the cost of the neonatal ICU/day. Direct current cardioversion remains cost-effective until the assumed conversion rate is below 64.6%. The most cost-efficient method of cardioverting a neonate with atrial flutter is direct current cardioversion. It has the highest success rates based on the meta-analysis, shorter length of stay in the neonatal ICU owing to its success, and results in cost-savings ranging from $800 to $4000 when compared with alternative approaches.

Baby-Friendly Practices Minimize Newborn Infants Weight Loss.

It is accepted that newborns lose weight in the first few days of life. Baby-Friendly practices that support breastfeeding may affect newborn weight loss. The objective of this study were: 1) To determine whether Baby-Friendly practices are associated with term newborn weight loss day 0-2 in three feeding categories (exclusively breastfed, mixed formula fed and breastfed, and formula fed). 2) To determine whether Baby-Friendly practices increase exclusive breast feeding rates in different ethnic populations. This was a retrospective case-control study. Term newborn birth weight, neonatal weights days 0-2, feeding type, type of birth, and demographic information were collected for 1,000 births for the year before Baby-Friendly designation (2010) and 1,000 in 2013 (after designation). Ultimately 683 in the first group and 518 in the second met the inclusion criteria. Mean weight loss decreased day 0-2 for infants in all feeding types after the initiation of Baby-Friendly practices. There was a statistically significant effect of Baby-Friendly designation on weight loss for day 0-2 in exclusively breastfed infants (p < 0.01) after controlling for birth weight. Exclusive breast feeding increased in all ethnic groups after Baby-Friendly practices were put in place. There was a decrease in mean weight loss day 0-2 regardless of feeding type after Baby-Friendly designation. Exclusive breast feeding increased in the presence of Baby-Friendly practices.

Immunohistochemical analyses of the kinetics and distribution of macrophages in the developing rat kidney.

Macrophages are required during kidney development and appear in the initiation and propagation of renal injury. To establish baseline data, we analyzed the kinetics of the macrophage with different immunophenotypes in the developing rat kidney (fetus at 18 and 20 days, neonate at 1-21 days, and adult at 7-weeks old). Macrophages reacting to CD68, CD163, and MHC class II were identified in the cortex and medulla of the developing rat kidney. CD68+ macrophages appeared in the fetal kidney as early as fetal day 18, and the number increased gradually in the neonatal kidney, whereas MHC class II+ and CD163+ macrophages first appeared on neonatal days 4 and 8, respectively. Apoptotic bodies were seen in the fetal kidney and early stages of the neonatal kidney (days 1–4), and simultaneously CD68+ macrophages appeared, indicating that CD68+ macrophages may have roles in phagocytosis of apoptotic bodies and contribute to renal tissue maturation. Colony stimulating factor 1 and insulin growth factor 1 mRNAs were increased in the late stage of renal development (neonatal day 12 or later), and simultaneously CD163+ and MHC class II+ cells appeared, suggesting that these cells may be a source of these growth factors and participate in renal tissue modeling. Generally, the CD163+ and MHC class II+ cell number was much smaller than that of CD68+ cells in the developing neonatal kidney. Therefore, the obtained findings provide valuable information on the participation of macrophages in the developing rat kidney. This information may be useful for evaluation of renal toxicity when macrophages are involved in the development of renal injury.

Neonatal Cholestasis: A Pandora's Box.

Neonatal cholestasis (NC) is a diagnostic dilemma frequently countered in a neonatal care unit. Early diagnosis is vital for achieving an optimal patient outcome as many causes of cholestasis such as biliary atresia are time-sensitive and amenable to treatment if analyzed and treated early. Nonetheless, it is not generally simple to analyze these cases right on time as some of them are regularly missed due to the presence of pigmented stools, lack of newborn metabolic screening, and named as instances of prolonged jaundice. In this manner, we prescribe to explore all reasons for prolonged jaundice stretching out past 14 days in neonates. Besides, we suggest that stool card ought to be a piece of release rundown for all newborn children being released from the nursery. This is of most extreme significance in the nation like India where guaranteeing customary follow-up is as yet a tough assignment. These stool cards will help in the early determination of patients with NC particularly biliary atresia and guarantee their auspicious cure. Another reason which needs exceptional say is parenteral nutrition–associated liver illness, as the proportion of preterm babies is getting greater and greater with better neonatal care. These extreme preterm infants are in the requirement for prolonged (>14 days) total parenteral nourishment because of which they are at high hazard for NC contrasted with their more developed peers. In this survey, we will give an understanding of clinical approach, differential diagnosis, and clinical review of NC.

Developmental Profiles of Hormonal and Metabolic Parameters in Male Rats Selected for Catatonic Type of Response

Catatonia is a psychopathological syndrome which manifests itself clinically mainly as motor disorders (dyskinesia). Currently, catatonia is believed to be associated with such human psychic conditions as schizophrenia, bipolar disorders and depression. Despite high incidence, catatonia remains poorly studied, especially with respect to hormonal and metabolic consequences. Modeling catatonic responses on laboratory animals and subsequent analysis of their relationship with expression of important physiological characters (including hormonal and metabolic ones) allow better insight into associative links between psychic and physiological functions of an organism. This work aimed to analyze the parameters of lipid metabolism and testicular steroidogenesis during the neonatal (days 1, 7, 10 and 14), pubertal (7 weeks) and definitive (12 weeks) periods of ontogeny in male rats selected for the catatonic type of response—GC strain recognized as a model of human schizophrenia and depression. During the perinatal developmental period, which is critical for the formation of neuroendocrine regulation, male rats exhibited an increased secretion of androgens (mainly testosterone) required for masculinization of brain structures and some peripheral organs including the reproductive and musculoskeletal systems. In GC male rats, the perinatal testosterone peak was found to shift towards later periods (compared to Wistar male rats) being paralleled by increased serum levels of triglycerides and total cholesterol. During the period of sexual maturation, adult male rats also exhibited differences in the testicular production of testosterone and in lipid levels between the GC and Wistar strains. Throughout the ontogenetic periods studied, GC male rats had a lower body and testicular weight than Wistar rats. The data obtained indicate that genetically determined neuropathological responses of an organism are coupled to the destabilization of the hormonal and metabolic systems.

Antibiotic exposure and development of necrotizing enterocolitis in very preterm neonates.

To examine the association between the duration of antibiotic exposure and development of stage 2 or 3 necrotizing enterocolitis (NEC) in very preterm neonates. A retrospective case-control study was conducted from Canadian Neonatal Network data for preterm neonates born before 29 weeks' gestation and admitted 2010 through 2013. Efforts were made to match each NEC case to two controls for gestational age, birth weight (±100 g) and sex. A total of 224 cases and 447 controls were identified. The incidence of antenatal steroid administration, the number of days nil-per-os and the number of antibiotic days prior to onset of NEC were significantly different in neonates with NEC. A multiple regression analysis revealed that the duration of antibiotic use was higher among NEC cases compared to controls (P<0.01). Empiric antibiotic treatment of 5 or more days was associated with significantly increased odds of NEC as compared with antibiotic exposure of 0 to 4 days (adjusted odds ratio: 2.02; 95% CI 1.55, 3.13). Empiric antibiotic exposure for 5 or more days in preterm neonates born before 29 weeks' gestation was associated with an increased risk of NEC.

Risk of Early-Onset Neonatal Group B Streptococcal Disease With Maternal Colonization Worldwide: Systematic Review and Meta-analyses.

BackgroundEarly-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0–6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS.MethodsWe conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage.ResultsWe identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%–1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0–.9).ConclusionsThe risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%–2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.

Clinical Outcome for Congenital Diaphragmatic Hernia at the Age of 1 Year in the Era of Fetal Intervention

Background: Congenital diaphragmatic hernia (CDH) is an abnormal development of the diaphragm leading to high neonatal mortality and morbidity. Beyond the neonatal period, prospective data on overall long-term outcome in CDH survivors is scarce. In particular, for those treated with fetoscopic endoluminal tracheal occlusion (FETO), a promising new technique to increase survival chances for severe cases, the outcomes are even less documented. Aim: To prospectively document the clinical outcome of CDH at 1 year including FETO-treated infants in relation to ante- and postnatal variables. Methods: A single-centre prospective clinical follow-up at 1 year of age included a standardised respiratory questionnaire. Results: Thirty-four CDH survivors were included, 10 of which were FETO-treated infants. At 1 year, the median weight z score was -1.50 (interquartile range [IQR]: -2.45 to -0.88) and 10/34 were “failure to thrive” (FTT) cases. Gastro-intestinal (GI) problems at 1 year were mainly related to gastro-oesophageal reflux (16/34) with a high need for tube feeding in the first year (9/34). Tachypnoea was present in 10/29 (34%) and 8/34 (24%) were on chronic inhaled medication. The median total respiratory symptom score was 20 (IQR: 13-32) and correlated with the number of neonatal ventilation days (p = 0.048). Hospital re-admission occurred in 19/34 infants (56%), and was for respiratory problems in almost half of them (8/19). Conclusion: In this CDH cohort, morbidity at 1 year was determined more by GI problems and FTT than respiratory morbidity. The respiratory questionnaire may, however, have underestimated the respiratory morbidity since respondents had a 1-in-4 chance to have persistent tachypnoea and be on chronic inhalation therapy.

Risk factors and molecular epidemiology of Acinetobacter baumannii bacteremia in neonates.

Acinetobacter baumannii infections in neonates are not uncommon but rarely studied. Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed. Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-blaOXA-80, which has never been reported in Asia before. Most infected newborns were premature (95%), with very low birth weight (70%<1500g), prolonged intubation, usage of percutaneous central venous catheter (65%) and long-term usage of total parenteral nutrition or intravenous lipid (95%). IRAB infection, inappropriate initial therapy, 1-minute Apgar score and early onset infection within the first 10 days of life were found to correlate with mortality by log-rank test. Prior use of imipenem for at least 5 days and use of high frequency oscillation ventilation (HFOV) were statistically significant risk factors for acquiring IRAB infections. To reduce mortality of IRAB infection, it is crucial to consider giving effective agents, such as colistin, in 2 days for high risk neonates who has been given imipenem or used HFOV.

Abstract 478: Cell-type Specific Surface Markers Effectively Isolate Cardiac Cell Sub-populations

Cardiomyocytes comprise only 20-30% of the cells in the heart. To enable downstream applications requiring live cells (including clinical application), identification of surface markers unique to all cardiac subpopulations is needed. Development of such strategies would create a powerful technique to tease apart the multiple cell populations that make up the heart and their role in complex heart diseases. Our hypothesis was that surface markers could be identified in neonatal mice to distinguish smooth muscle cells (SMC), cardiomyocytes (CM), fibroblasts (FB) and endothelial cells (EC), enabling sorting by flow cytometry and analysis of these subpopulations of heart cells. Hearts were surgically removed from one litter of neonatal (Day 0-2) C57BL/6J mice and three litters of transgenic mice with mCherry α-myosin heavy chain promoter (αMHC-mCherry), then digested with trypsin overnight followed by collagenase/dispase and gentle mechanical dissociation. Surface marker staining for Cadherin-2 (Cdh2) showed congruence with αMHC-mCherry positivity. Cells were sorted using fluorescent activated cell sorting with antibodies against the following surface markers: Cdh2 (CM), CD31 (EC), CD90.2 (FB) and CD49a (SMC). Enrichment of these cell populations was then evaluated by qRT-PCR for known intracellular and extracellular markers specific to each cell: EC (CD31 + vWf), CM (TNNT2 + Myh6), FB (CD90) and SMC (Myh10/11 + Tagln). Our panel of surface markers enabled enrichment of four subpopulations of heart cells which will be verified further in coming experiments. In the future, this strategy will enable sorting of cells from each subpopulation for downstream analysis.