Complication Of Premature Birth Research Articles

Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport.

Intraventricular hemorrhage (IVH) is a common complication of premature birth. Survivors are often left with cerebral palsy, intellectual disability, and/or hydrocephalus. Animal models suggest that brain tissue shrinkage with subsequent vascular stretch and tear is an important step in the pathophysiology, but the cause of this shrinkage is unknown. Clinical risk factors for IVH are biomarkers of hypoxic-ischemic stress, which causes mature neurons to swell. However, immature neuronal volume might shift in the opposite direction under these conditions. This is because immature neurons express the chloride salt and water transporter NKCC1, which subserves regulatory volume increases in nonneural cells, whereas mature neurons express KCC2, which subserves regulatory volume decreases. When hypoxic ischemic conditions reduce active ion transport and increase the cytoplasmic membrane permeability, the effects of these transporters will be diminished. As a consequence, while mature neurons swell (cytotoxic edema) immature neurons might shrink. After hypoxic-ischemic stress, in vivo and in vitro multi-photon imaging of perinatal transgenic mice demonstrated shrinkage of viable immature neurons, bulk tissue shrinkage, and blood vessel displacement. Neuronal shrinkage was correlated with age-dependent membrane salt and water transporter expression using immunohistochemistry. Shrinkage of immature neurons was prevented by prior genetic or pharmacological inhibition of NKCC1 transport. These findings open new avenues of investigation for the detection of acute brain injury by neuroimaging, as well as prevention of neuronal shrinkage and the ensuing IVH, in premature infants.

How Did the COVID-19 Pandemic Affect Maternal and Neonatal Health?

The aim of this study was to investigate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the proportional growth of the fetus, maternal health, and neonatal outcomes. The study group (Group 1) included pregnant women with a history of COVID-19. Pregnant women who were hospitalized during the same period without COVID-19 were the control group (Group 2). Maternal and neonatal outcomes were compared between the groups. A total of 230 pregnant women and their infants were assessed. Group 1 (n = 74) had significantly higher rates of diabetes mellitus and hypertension than Group 2 (n = 156; p = 0.015 and 0.014, respectively). Premature birth and cesarean section rates were also significantly higher in Group 1 than in Group 2 (p = 0.001 and 0.040, respectively). While the rate of iatrogenic preterm birth was significantly higher in Group 1, the rate of spontaneous preterm birth was significantly higher in Group 2 (p = 0.049). Infants born to COVID-19-positive mothers had lower median gestational age, birth weight, and Apgar scores (p < 0.01). There was no significant difference between the groups in terms of the results of cord blood gas analysis (p > 0.05). The rate of admission to the neonatal intensive care unit (NICU) and need for mechanical ventilation was significantly higher in infants of COVID-19-positive mothers (p < 0.05 for both). The length of stay in the NICU was also significantly longer for the infants of COVID-19-positive mothers (p < 0.05). Birth weights decreased due to increased cases of iatrogenic preterm births (p < 0.05). However, ponderal indices (PIs) of newborns of pregnant COVID-19 mothers did not differ at birth (p > 0.05). COVID-19 is associated with low Apgar scores, increased risk of premature birth complications, and maternal comorbidities, with no effect on the PI and proportionate growth of the infant at birth. · No difference in ponderal indices.. · No difference in postnatal cardiovascular adaptation.. · COVID-19 is frequent in pregnant women with comorbidities like diabetes mellitus and hypertension..

The effect of Daikenchuto on blood flow of the superior mesenteric artery and portal vein in ELBW: A prospective study.

Focal intestinal perforation (FIP) is a devastating complication of premature birth, and extremely low birth weight (ELBW) infants are at highest risk. This study aimed to evaluate the relationship of the superior mesenteric artery (SMA) and portal vein (PV) blood flow velocities to investigate the association between intestinal blood flow and FIP. In addition, the herbal formula Daikenchuto (TJ-100) is expected to improve intestinal blood flow disorders; therefore, we evaluated its effect. We conducted a prospective cohort study of 15 ELBW infants from January 2020 to August 2021. Measured variables included birth weight, 5-minute Apgar score, time of oral feeding initiation, ductus arteriosus (PDA) closure (percent), diastolic and systolic blood pressure, SMA and PV blood flow velocity, and FIP onset data. Fifteen infants were divided into three groups: a non-surgery group (Group I; 6), a surgery group with FIP (Group II; 4), and a TJ-100 administration group (Group III; 5). The main outcome parameters included SMA and PV blood flow velocities with TJ-100. SMA and PV blood flow differed significantly for the SMA of Group I and the SMA and PV of Group III (P < 0.01, P = 0.01, and P = 0.04, respectively). There was a correlation between SMA and PV in Group III (P = 0.03). TJ-100 may increase SMA and PV blood flow and improve intestinal blood flow in ELBW infants at risk of FIP. Therefore, the effects of TJ-100 should undergo further study.

Pulmonary phenotypes of bronchopulmonary dysplasia in the preterm infant

Bronchopulmonary dysplasia (BPD) remains the most common complication of premature birth, imposing a significant and potentially life-long burden on patients and their families. Despite advances in our understanding of the mechanisms that contribute to patterns of lung injury and dysfunctional repair, current therapeutic strategies remain non-specific with limited success. Contemporary definitions of BPD continue to rely on clinician prescribed respiratory support requirements at specific time points. While these criteria may be helpful in broadly identifying infants at higher risk of adverse outcomes, they do not offer any precise information regarding the degree to which each compartment of the lung is affected. In this review we will outline the different pulmonary phenotypes of BPD and discuss important features in the pathogenesis, clinical presentation, and management of these frequently overlapping scenarios.

Sodium and Growth in Preterm Infants: A Review.

This article is intended to review the relationship between sodium homeostasis and growth, outline reasons why preterm infants may become sodium deficient, and share data from our group and others regarding the potential benefits of dietary sodium supplementation. Despite tremendous efforts over the past 20 years to optimize neonatal nutrition, postnatal growth failure in preterm infants remains a significant problem. Compelling associations have been identified between in-hospital growth failure and cardiometabolic and neurodevelopmental disorders, heightening the need to further identify the optimal nutritional needs of preterm infants. The impact of sodium deficiency may have on somatic growth is poorly studied and reported upon within the human literature. In contrast, animal studies dating back almost 100 years highlight the nutritional importance of dietary sodium. Sodium homeostasis during early postnatal life is understudied and underappreciated by neonatologists. Insufficient sodium intake during early life is likely a critical yet underappreciated contributor to growth failure. Total body sodium depletion may be an important risk factor driving complications of premature birth. Increased awareness of sodium homeostasis in preterm infants may improve outcomes in this population. Sodium intake recommendations are provided based on the interpretation of currently available literature.

Incidence of Retinopathy of Prematurity in Neonates with Neonatal Sepsis.

One of the most important complications of premature birth is retinopathy of prematurity (ROP). Sepsis may increase the incidence of this complication. The aim of this study is to compare the incidence of ROP in neonates with and without sepsis. In a retrospective case-control study, preterm infants admitted to the neonatal intensive care unit (NICU) of Ghaem hospital from 2014 to 2022 were examined. The case group consisted of 155 preterm infants with definite sepsis (positive blood culture and clinical signs of sepsis) and the control group included 145 preterm infants without sepsis whose maternal and neonatal characteristics were collected; they were examined by a retinologist and evaluated for ROP at 32 weeks or four weeks after birth. Finally, we used the chi-square and the t test to compare the two groups. Out of 155 preterm infants with sepsis, 70% and out of 145 preterm infants without sepsis, 58% had ROP (P=0.023). Also, low birth weight, low initial Apgar score and low 5-minute Apgar score were significantly associated with ROP (P<0.05). Based on the results of this study, sepsis is a serious risk factor for ROP. We can reduce its incidence and complication by preventing sepsis in premature infants.

Delivery decision in pregnant women rescued by ECMO for severe ARDS: a retrospective multicenter cohort study

BackgroundAlthough rarely addressed in the literature, a key question in the care of critically pregnant women with severe acute respiratory distress syndrome (ARDS), especially at the time of extracorporeal membrane oxygenation (ECMO) decision, is whether delivery might substantially improve the mother’s and child’s conditions. This multicenter, retrospective cohort aims to report maternal and fetal short- and long-term outcomes of pregnant women with ECMO-rescued severe ARDS according to the timing of the delivery decision taken before or after ECMO cannulation.MethodsWe included critically ill women with ongoing pregnancy or within 15 days after a maternal/child-rescue-aimed delivery supported by ECMO for a severe ARDS between October 2009 and August 2021 in four ECMO centers. Clinical characteristics, critical care management, complications, and hospital discharge status for both mothers and children were collected. Long-term outcomes and premature birth complications were assessed.ResultsAmong 563 women on venovenous ECMO during the study period, 11 were cannulated during an ongoing pregnancy at a median (range) of 25 (21–29) gestational weeks, and 13 after an emergency delivery performed at 32 (17–39) weeks of gestation. Pre-ECMO PaO2/FiO2 ratio was 57 (26–98) and did not differ between the two groups. Patients on ECMO after delivery reported more major bleeding (46 vs. 18%, p = 0.05) than those with ongoing pregnancy. Overall, the maternal hospital survival was 88%, which was not different between the two groups. Four (36%) of pregnant women had a spontaneous expulsion on ECMO, and fetal survival was higher when ECMO was set after delivery (92% vs. 55%, p = 0.03). Among newborns alive, no severe preterm morbidity or long-term sequelae were reported.ConclusionContinuation of the pregnancy on ECMO support carries a significant risk of fetal death while improving prematurity-related morbidity in alive newborns with no difference in maternal outcomes. Decisions regarding timing, place, and mode of delivery should be taken and regularly (re)assess by a multidisciplinary team in experienced ECMO centers.

Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated With Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response. Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort. A total of 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed with paired analysis of pre and post-treatment samples using Wilcoxon signed rank test. Correlation analysis was conducted between deltaRSS and pre-to-post change in metabolite level. Paired association analysis identified 20 plasma and 26 urine metabolites with significant level difference comparing pre to post treatment samples (p < 0.05). 4 plasma and 4 urine metabolites were also significant in the original study. Pre-to-post treatment change in metabolite analysis identified 4 plasma and 8 urine metabolites significantly associated with deltaRSS (p < 0.05). Change in urine citrulline levels showed a similar correlation pattern with deltaRSS in the first study, with increasing level associated with improved drug response. These results help validate the first major findings from pharmacometabolomics of BPD including key metabolites within the urea cycle and trans-4-hydroxyproline as a potential marker for lung injury. Ultimately, this study furthers our understanding of the mechanisms of steroid response in BPD patients and helps to design future targeted metabolomics studies in this patient population.

Knowledge, Attitude, and Practice using the Kangaroo Method Care in Maternal with Low Birth Weight Babies

Newborn mortality is still quite high in the world, including Indonesia, one of which is caused by complications of premature birth. Kangaroo Method Care (KMC) is one way to keep the newborn’s body temperature warm by making direct contact between the baby’s skin and the mother’s skin. The purpose of this study was to analyze the relationship between knowledge, attitude, and practice of Kangaroo Care Method for mothers with low birth weight (LBW) infants. This study is a quantitative study with a cross-sectional approach. Respondents in this study were mothers who had LBW after treatment from the Regional General Hospital (RSUD) Koja, North Jakarta who were domiciled in Koja, Tanjung Priok, and Cilincing Districts, North Jakarta, amounting to 50 people. Data was collected using questionnaires and observations, and analyzed using the Spearman Correlation statistical test. Based on the results of the study, the average score of mother’s knowledge about Kangaroo Care Method was 21.76 (SD 1.06); the average score of the mother’s attitude towards the Kangaroo Care Method is 26.74 (SD 0.80); and the average duration of practice for Kangaroo Care Method is 2.92 hours/day (SD 0.90). Based on the results of observations, it was found that most of the LBW mothers had practiced Kangaroo Method Care by holding the right position from Kangaroo Method Care. Based on the Spearman Correlation statistical test, it was found that there was a relationship between knowledge, attitude, and practice of the Kangaroo Care Method in LBW mothers.

INCU Analyzer for Infant Incubator Based on Android Application Using Bluetooth Communication to Improve Calibration Monitoring

Worldwide, over 4 million babies die within a month of birth each year. Of these, 3.9 million are in developing countries. A proportion approximately 25% of these deaths are due to complications of premature birth, most commonly inadequate thermoregulation, water loss, and neonatal jaundice. An infant incubator provides stable temperature, relative humidity, and airflow values. A periodical calibration should be applied on infant incubator to monitor the functionality. The study aims to develop a calibration device that measures temperature, humidity, airflow, and noise in the baby incubator based on an Android application with Bluetooth communication to improve the calibration monitoring process. This is to achieve a better performance of the conventional INCU analyzer. The contribution of this research is that the values of the temperature, humidity, airflow, and noise can be displayed on both devices, the INCU analyzer machine, and mobile phone; thus, the user can monitor the measurement activities wirelessly. Furthermore, the statistical calculation for all measurements can be saved on a mobile phone device. The main design consists of temperature sensor LM35, humidity sensor DHT22, airflow sensor MPX5010DP, an analog signal conditioning circuit, an Arduino Mega microcontroller, Bluetooth module HC05, and Android mobile phone. The resulting design was compared to the standard or calibrator INCU analyzer machine (Fluke Biomedical INCU II). This study found that the smallest error is -1.72%°C, -0.106 % RH, -1.727% dB, and &lt;0.1% m/s for temperature, humidity, noise, and airflow parameters, respectively. After the evaluation process, this device can be used as an INCU analyzer to calibrate the infant incubator.

Accounting for arterial and capillary blood gases for calculation of cerebral blood flow in preterm infants

One of the most feared neurological complications of premature birth is intraventricular hemorrhage, frequently triggered by fluctuations in cerebral blood flow (CBF). Although several techniques for CBF measurement have been developed, they are not part of clinical routine in neonatal intensive care. A promising tool for monitoring of CBF is its numerical assessment using standard clinical parameters such as mean arterial pressure, carbon dioxide partial pressure (pCO2) and oxygen partial pressure (pO2). A standard blood gas analysis is performed on arterial blood. In neonates, capillary blood is widely used for analysis of blood gas parameters. The purpose of this study was the assessment of differences between arterial and capillary analysis of blood gases and adjustment of the mathematical model for CBF calculation to capillary values. The statistical analysis of pCO2 and pO2 values collected from 254 preterm infants with a gestational age of 23–30 weeks revealed no significant differences between arterial and capillary pCO2 and significantly lower values for capillary pO2. The estimated mean differences between arterial and capillary pO2 of 15.15 mmHg (2.02 kPa) resulted in a significantly higher CBF calculated for capillary pO2 compared to CBF calculated for arterial pO2. Two methods for correction of capillary pO2 were proposed and compared, one based on the mean difference and another one based on a regression model.Conclusion: Capillary blood gas analysis with correction for pO2 as proposed in the present work is an acceptable alternative to arterial sampling for the assessment of CBF.What is Known:• Arterial blood analysis is the gold standard in clinical practice. However, capillary blood is widely used for estimating blood gas parameters.• There is no significant difference between the arterial and capillary pCO2values, but the capillary pO2differs significantly from the arterial one.What is New:• The lower capillary pO2values yield significantly higher values of calculated CBF compared to CBF computed from arterial pO2measurements.• Two correction methods for the adjustment of capillary pO2 to arterial pO2that made the difference in the calculated CBF insignificant have been proposed.

Abstract 13167: Multiscale Mechanisms of Right Ventricular Injury in Bronchopulmonary Dysplasia

Introduction: Bronchopulmonary dysplasia (BPD) is the most common complication of premature birth. Whether right ventricular (RV) injury or chronically increased afterload are more responsible for long-term RV dysfunction in BPD is unknown. We aim to determine key drivers of RV dysfunction in BPD using both experimental data and a computational model. We hypothesize that decreased mitochondrial energetics and active force generation are critical contributors. Methods: Male and female Sprague-Dawley rats were delivered at term to timed-pregnant dams and exposed to either room air (Nx) or 85% fraction inspired O 2 (Hx) for 4, 8, or 14 days. Multiscale experimental data was obtained at postnatal day 21 and used to parameterize the previously published computational model of the heart and circulation, which integrates myocardial mechanics and mitochondrial energetics. Results: Despite increased RV afterload in the 8-and 14-day exposure groups (Fig. 1A) and significant RV hypertrophy in the 14-day group (Fig. 1B), there was no change in ejection fraction (EF) due to high variability (Fig. 1C). We used the computational model to explore how multiscale features of RV injury impact RV EF (Fig. 1D). Whereas decreased mitochondrial function, decreased cross-bridge maximum force, and increased RV afterload further reduce predicted RV EF in the 14-day Hx rat with the lowest EF (red symbol) and RV EF in the 14-day Nx rat with the highest EF (blue symbol), EF can be restored in a simulated reversal of these injuries in the Hx rat. Conclusions: Our approach provides valuable insight into key features of RV injury in BPD. Different degrees and combination of injuries at multiple scales can explain functional heterogeneity and may enable more accurate predictions of long-term RV dysfunction. Figure 1: Measurements of (A) RV afterload, (B) RV Fulton index and (C) RV EF as well as computational model predictions of (D) RV EF for one 14D Hx (red) and one 14D Nx rat (blue).

Extreme Prematurity and Pulmonary Outcomes Program in Saitama: Protocol for a Prospective Multicenter Cohort Study in Japan.

BackgroundBecause of the improvements in survival rates for preterm infants, not only the rates of bronchopulmonary dysplasia (BPD) but also those of long-term respiratory complications of premature birth are increasing, resulting in financial and health burdens in developed countries. Thus far, the risk factors of respiratory morbidities in extremely preterm infants remain unknown. Furthermore, the definition and the predictive ability of BPD for long-term respiratory outcomes are yet to be determined.ObjectiveThe objective of our study, Extreme Prematurity and Pulmonary Outcomes Program in Saitama, is to develop the diagnostic criteria for BPD and to determine the prognostic factors contributing to the long-term pulmonary outcomes manifesting in extremely preterm infants.MethodsThe Extreme Prematurity and Pulmonary Outcomes Program in Saitama is an observational prospective cohort study performed by a consortium of six neonatal intensive care units (NICUs) in Saitama, Japan. The subjects included in this study are infants (from each clinical center) with gestational ages 22 to 27 weeks. The target is 400 subjects. This study aims to determine the definition of BPD and other perinatal factors that accurately predict the long-term pulmonary outcomes in survivors of extreme prematurity. Moreover, the association between BPD and postprematurity respiratory disease will be investigated using generalized linear models.ResultsThe protocol and consent forms were evaluated and approved on September 5, 2019, by the Ethics Committee of Saitama Medical Center, Saitama Medical University. Enrollment began on April 1, 2020. It is expected to end on March 31, 2023. The follow-up for 1 year corrected age is expected to continue through the middle of 2024.ConclusionsThe Extreme Prematurity and Pulmonary Outcomes Program in Saitama incorporates aspects of neonatal care in secondary- and tertiary-level NICUs to develop existing research studies on the definition of BPD, objective biomarkers, and outcome measures of respiratory morbidity in extremely preterm infants beyond NICU hospitalization, thereby leading to a novel understanding of the nature and natural history of BPD and potential mechanistic and therapeutic targets in at-risk subjects.International Registered Report Identifier (IRRID)DERR1-10.2196/22948

Predictors of pulmonary function at 6 years of age in infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth and the most common cause of chronic lung disease in infancy. Previous studies have shown that children with a history of BPD have impaired lung function in childhood compared to their term counterparts. However, little is known about potential modifiable factors that alter lung function trajectories and subsequent respiratory morbidity in this population. To identify potential modifiable risk factors for the development of impaired lung function in patients with a history of prematurity and bronchopulmonary dysplasia. Growth parameters (birth, 2 years old, 6 years old) and pulmonary function testing (6 years old) were retrospectively reviewed for subjects (n = 598) recruited from an outpatient BPD clinic who were born ≤36 weeks gestation and were≥5 years of age. Of the 598 recruited subjects, 88 (14.7%) performed adequate pulmonary function testing at approximately 6 years of age. The mean forced expiratory volume in 1 s global lung initiative (GLI) Z-score was -1.31 with lower values associated with Nissen fundoplication. The mean forced vital capacity GLI Z-score was -0.72 with lower values associated with higher amounts of oxygen required at time of initial hospital discharge and Nissen fundoplication. Our study found that children with BPD have lower predicted lung function values. Although growth parameters at age 2 and 6 years did not correlate with lung function values at 6 years of age; use and greater requirement for supplemental oxygen and the presence of a Nissen fundoplication at discharge were associated with lower lung function. Prospective studies should focus on identifying modifiable risk factors that could minimize the impact of BPD on later lung function.

Prematurity blunts the insulin- and amino acid-induced stimulation of translation initiation and protein synthesis in skeletal muscle of neonatal pigs.

Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days, n = 25) or at term (T; 112 days, n = 26) were subject to euinsulinemic-euaminoacidemic-euglycemic (FAST), hyperinsulinemic-euaminoacidemic-euglycemic (INS), or euinsulinemic-hyperaminoacidemic-euglycemic (AA) clamps four days after delivery. Indices of mechanistic target of rapamycin complex 1 (mTORC1) signaling and fractional protein synthesis rates were measured after 2 h. Although longissimus dorsi (LD) muscle protein synthesis increased in response to both INS and AA, the increase was 28% lower in PT than in T. Upstream of mTORC1, Akt phosphorylation, an index of insulin signaling, was increased with INS but was 40% less in PT than in T. The abundances of mTOR·RagA and mTOR·RagC, indices of amino acid signaling, increased with AA but were 25% less in PT than in T. Downstream of mTORC1, eIF4E·eIF4G abundance was increased by both INS and AA but attenuated by prematurity. These results suggest that preterm birth blunts both insulin- and amino acid-induced activation of mTORC1 and protein synthesis in skeletal muscle, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the high prevalence of extrauterine growth restriction in prematurity.NEW & NOTEWORTHY Extrauterine growth faltering is a major complication of premature birth, but the underlying cause is poorly understood. Our results demonstrate that preterm birth blunts both the insulin-and amino acid-induced activation of mTORC1-dependent translation initiation and protein synthesis in skeletal muscle, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced accretion of lean mass and extrauterine growth restriction of premature infants.

NeoWarm: Kangaroo Mother Care with Continuous Temperature Tracking and Heating.

Premature births are highly prevalent; world-wide, one in every ten births is premature. A common complication of premature birth is the inability of the newborns to regulate their own body temperature (hypothermia). Kangaroo Mother Care (KMC) is an effective strategy to mitigate this problem but has challenges. Namely, KMC requires constant engagement from the caregiver in order to keep the baby warm and to monitor the baby's temperature every 4 hours. In this report we describe NeoWarm, a device designed to address these challenges via continuous integrated warming and automated temperature monitoring of the infant, both during KMC and when the caregiver takes a break. Pilot studies demonstrate the ability of the device to warm a simulated newborn from moderate hypothermia to ideal core temperatures within two hours.

Prematurity Alters the Feeding-Induced Activation of Signaling Components Towards AKT in Skeletal Muscle of Neonatal Piglets

Abstract Objectives Postnatal growth faltering is a common complication of premature birth. Our recent study in a neonatal pig model of prematurity showed that preterm birth reduces weight gain and protein synthesis in skeletal muscle and this is associated with blunted insulin-induced activation of signaling components downstream of AKT. However, prematurity does not affect the activation of the IR/IRS-1/PI3K axis. In this study, we aimed to identify components in the AKT signaling pathway in skeletal muscle that underlie the differential response to insulin between preterm and term pigs. Methods Cesarean-derived piglets delivered 11 d (preterm) or 2 d (term) before term were fitted with a jugular vein catheter for delivery of total parenteral nutrition. On day 3, all piglets were fasted for 4 h and then assigned randomly to fast one additional h or to receive an elemental meal by oral gavage. Macronutrient content of the elemental meal mimicked sow milk composition at day 3 of lactation. Piglets were euthanized for tissue collection in the fasted state or 60 min after feeding. The longissimus dorsi muscle was collected and subjected to Western blot and immunoprecipitation assays for analyzing upstream regulators of AKT activity. Results Phosphorylation of PDK1 and mTORC2 was lower in preterm than term pigs (P &amp;lt; 0.05). The abundance of phosphatase PHLPP, but not PTEN, was significant higher in preterm than term pigs (P &amp;lt; 0.05). Preterm pigs had lower PP2A activation (P &amp;lt; 0.05), but its activation was not affected by feeding, unlike term pigs where feeding inhibited PP2A activation (P &amp;lt; 0.05). The abundance of Ubl4A, required for insulin-induced translocation of AKT to the plasma membrane, was reduced by prematurity (P &amp;lt; 0.05). While AKT1 abundance was higher in preterm than term pigs (P &amp;lt; 0.05), the abundances of both AKT2 and AKT3 were lower in preterm than term pigs (P &amp;lt; 0.05). Conclusions Our results demonstrate that prematurity reduces the abundance and/or activation of positive regulators of AKT such as Ubl4A, PDK1, and mTORC2. Conversely, prematurity increased the activation of AKT inhibitors such as PHLPP and PP2A. Our findings potentially pave the way for a better understanding of the mechanisms that underlie postnatal growth faltering in premature infants. Funding Sources NIH and USDA.

Microbiological analyses of nasally guided catheters after less invasive surfactant administration \u2013 a pilot study

BackgroundRespiratory distress syndrome (RDS) is a frequent complication of premature birth. Treating RDS by continuous positive airway pressure and less invasive surfactant administration (LISA) may reduce bronchopulmonary dysplasia. Surfactant, however, can be inactivated by bacterial infection. Therefore, potential routes of microbe transmission into the airway are of interest. The aim of this study was to evaluate microbiological contamination of catheters used for LISA procedures and its association with postnatal age.MethodsCatheter tips used for LISA procedures via the nasal route (LISA-n) in infants with RDS were placed into a sterile eSwab container directly after the procedure, cultured and examined for microbiological contamination.ResultsInterpretable results could be collected from 20 catheter tips. Four showed positive culture results (20%) with microbes potentially associated with the development of early onset neonatal sepsis. Risk of positive microbe detection increased with postnatal age (< 4 h: 10%; 4–18 h: 20%; > 18 h: 40%).ConclusionsIn this pilot study, the risk of tracheal microbe transmission following the LISA-n procedure increased with postnatal age. Although the clinical relevance of this finding is unclear, earlier surfactant administration might reduce the risk of catheter contamination.Trial registration numberSubstudy of the registered Trial: feasibility study – Neofact: NCT04086095, www.ClinicalTrials.gov, September 11, 2019.

Novel Strategies to Reduce Pulmonary Hypertension in Infants With Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a developmental lung disorder of preterm infants primarily caused by the failure of host defense mechanisms to prevent tissue injury and facilitate repair. This disorder is the most common complication of premature birth, and its incidence remains unchanged over the past few decades. Additionally, BPD increases long-term cardiopulmonary and neurodevelopmental morbidities of preterm infants. Pulmonary hypertension (PH) is a common morbidity of BPD. Importantly, the presence of PH increases both the short- and long-term morbidities and mortality in BPD infants. Further, there are no curative therapies for this complex disease. Besides providing an overview of the pathogenesis and diagnosis of PH associated with BPD, we have attempted to comprehensively review and summarize the current literature on the interventions to prevent and/or mitigate BPD and PH in preclinical studies. Our goal was to provide insight into the therapies that have a high translational potential to meaningfully manage BPD patients with PH.

Assessing key clinical parameters before and after intraventricular hemorrhage in very preterm infants

Intraventricular cerebral hemorrhage (IVH) is one of the most severe complications of premature birth, potentially leading to lifelong disability. The purpose of this paper is the assessment of the evolution of three of the most relevant parameters, before and after IVH: mean arterial pressure (MAP), arterial carbon dioxide pressure (pCO2), and cerebral blood flow (CBF). Clinical records of 254 preterm infants with a gestational age of 23–30 weeks, with and without a diagnosis of IVH, were reviewed for MAP and arterial pCO2 in the period up to 7 days before and 3 days after IVH or during the first 10 days of life in cases without IVH.Conclusion: A statistically significant increase in pCO2 and decrease in MAP in patients with IVH compared with those without were detected. Both the mean values and the mean absolute deviations of CBF were computed in this study, and the latter was significantly higher than in control group. High deviations of CBF, as well as hypercapnia and hypotension, are likely to contribute to the rupture of cerebral blood vessels in preterm infants, and consequently, to the development of IVH.What is Known:• The origin of IVH is multifactorial, but mean arterial pressure, carbon dioxide partial pressure, and cerebral blood flow are recognized as the most important parameters.• In premature infants, the autoregulation mechanisms are still underdeveloped and cannot compensate for cerebral blood flow fluctuations.What is New:• The numerical simulation of CBF is shown to be a promising approach that may be useful in the care of preterm infants.• The mean values of CBF before and after IVH in the affected group were similar to those in the control group, but the mean absolute deviations of CBF in the affected group before and after IVH were significantly higher than that in the control group.