scholarly journals Chorioamnionitis in Rats Precipitates Extended Postnatal Inflammatory Lymphocyte Hyperreactivity

2018 ◽  
Vol 40 (5-6) ◽  
pp. 523-533 ◽  
Author(s):  
Tracylyn R. Yellowhair ◽  
Shahani Noor ◽  
Brittney Mares ◽  
Clement Jose ◽  
Jessie C. Newville ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Fetal Brain ◽  
In Utero ◽  
Placental Insufficiency ◽  
Neurological Injury ◽  
Perinatal Brain Injury ◽  
Inflammatory Signaling ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Preterm birth is an important cause of perinatal brain injury (PBI). Neurological injury in extremely preterm infants often begins in utero with chorioamnionitis (CHORIO) or inflammation/infection of the placenta and concomitant placental insufficiency. Studies in humans have shown dysregulated inflammatory signaling throughout the placental-fetal brain axis and altered peripheral immune responses in children born preterm with cerebral palsy (CP). We hypothesized that peripheral immune responses would be altered in our well-established rat model of CP. Specifically, we proposed that isolated peripheral blood mononuclear cells (PBMCs) would be hyperresponsive to a second hit of inflammation throughout an extended postnatal time course. Pregnant Sprague-Dawley dams underwent a laparotomy on embryonic day 18 (E18) with occlusion of the uterine arteries (for 60 min) followed by intra-amniotic injection of lipopolysaccharide (LPS, 4 μg/sac) to induce injury in utero. Shams underwent laparotomy only, with equivalent duration of anesthesia. Laparotomies were then closed, and the rat pups were born at E22. PBMCs were isolated from pups on postnatal day 7 (P7) and P21, and subsequently stimulated in vitro with LPS for 3 or 24 h. A secreted inflammatory profile analysis of conditioned media was performed using multiplex electrochemiluminescent immunoassays, and the composition of inflammatory cells was assayed with flow cytometry (FC). Results indicate that CHORIO PBMCs challenged with LPS are hyperreactive and secrete significantly more tumor necrosis factor α (TNFα) and C-X-C chemokine ligand 1 at P7. FC confirmed increased intracellular TNFα in CHORIO pups at P7 following LPS stimulation, in addition to increased numbers of CD11b/c immunopositive myeloid cells. Notably, TNFα secretion was sustained until P21, with increased interleukin 6, concomitant with increased expression of integrin β1, suggesting both sustained peripheral immune hyperreactivity and a heightened activation state. Taken together, these data indicate that in utero injury primes the immune system and augments enhanced inflammatory signaling. The insidious effects of primed peripheral immune cells may compound PBI secondary to CHORIO and/or placental insufficiency, and thereby render the brain susceptible to future chronic neurological disease. Further understanding of inflammatory mechanisms in PBI may yield clinically important biomarkers and facilitate individualized repair strategies and treatments.

Safety of Allogenic Human Cord Blood Derived Mononuclear Cells for Extreme Preterms Infants at High Risk of Death: A Descriptive Study

2020 ◽  
Author(s):  
Jia Chen ◽  
Yabo Mei ◽  
Xue Du ◽  
Qiuping Li ◽  
Zizhen Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Preterm Infants ◽  
Mononuclear Cells ◽  
Human Umbilical Cord ◽  
Risk Of Death ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Risk Potential

Abstract Backgroud Extreme preterm infants are at a high risk for developing preterm complications and death. Despite advances in medical care, many survivors face a lifetime of disability. Objective To assess the short term safety of and four-year follow-up outcomes of allogenic, human umbilical cord blood (hUCB) derived mononuclear cells(MNCs) infusion to extreme preterm infants with high risk potential of death. Method This study was a phase I, open-label, single-arm, single-center trial to evaluate the safety of allogenic, hUCB-MNCs infusion for extreme preterm infants with high risk potential of death. HUCB MNCs characteristics, pre- and postinfusion vital signs and laboratory investigations were recorded. Temporal profiles of cytokines and growth factors from blood were test. Clinical data including mortality rates, preterm complications and follow-up outcomes were recorded. Results After processing, relatively MNCs mean (1.9±0.8) ×106/kg; volume mean (11.25±2.12)ml/kg were infused to 10 extremely preterm infants with high risk of death. No adverse effects were noticed during treatment. 40% received extubation and weaned to nasal CPAP successfully; 30% received lower FiO2; no infants suffered from late onset sepsis; 30% received poor response to MNCs infusion. 40% infants suffered from ROP and only one infant needed laser surgery. No patients suffered from NEC after MNCs infusion. All ten infants who received hUCB MNCs infusion survived inhospital and prevent deterioration of clinical features, but 4 infants discharged against the advice of the doctor by their parents and lost connection. Regarding the rest 6 infants, no home oxygen therapy and rehospitalization, no suffered from other long-term respiratory complications at visit 1～visit 3. One infant showed cerebral palsy at visit 1, no clinical evidence associated this with MNCs infusion. Blood level of HGF significantly increased, but MMP-9, IL-6, IL-8, TNF-α and TGF-β levels were significantly lower at 24h post infusion compared with baseline (P < 0.05).Conclusions Collection, preparation, and infusion of allogenic hUCB MNCs to extreme preterm infants is feasible and safe. Trial registration The study was registered on Chinese Clinical Trials.gov (NO. ChiCTR–OPN - 15006932). Registered 17 August 2015, http://www.chictr.org.cn/edit.aspx?pid=11662&htm=4.

64 Association of 24-hour In-house Neonatologist Coverage with Outcomes of Extremely Preterm Infants

2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e45-e46
Author(s):  
Anthony Debay ◽  
Prakesh Shah ◽  
Abhay Lodha ◽  
Sandesh Shivananda ◽  
Stephanie Redpath ◽  
...  
Keyword(s):  
Late Onset ◽  
Neurological Injury ◽  
Multivariable Logistic Regression Analysis ◽  
Care Providers ◽  
Chest Compressions ◽  
Perinatal Medicine ◽  
Major Morbidity ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Care Practices

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Medical team composition at the delivery of high-risk neonates may contribute to better outcomes. The presence of 24-hour (h) in-house staff neonatologist (NN) may improve delivery room (DR) care practices and outcomes. Objectives To assess if 24-h in-house NN coverage is associated with better care practices and outcomes among inborn infants born &lt; 29 weeks GA. Design/Methods Cross-sectional cohort study of 2476 inborn infants born at 23-28 weeks gestation, admitted in 2014-2015 to Canadian Neonatal Network level 3 NICUs with a maternity unit that participated in a 2015 survey on NICU coverage. Exposures were classified using survey responses based on the most senior provider offering 24-h in-house coverage: NN, fellow, and no NN/fellow. Primary outcome was death and/or major morbidity (bronchopulmonary dysplasia, severe neurological injury, late-onset sepsis, necrotizing enterocolitis, retinopathy of prematurity). Multivariable logistic regression analysis was used to assess the association between exposures and outcomes and adjust for confounders with generalized estimating equations to account for clustering within each site. Results Among the 28 participating NICUs, most senior providers ensuring 24-h in-house coverage were NN (32%, 9/28), fellows (39%, 11/28), and no NN/fellow (29%, 8/28). Infants’ characteristics are shown in Table 1. No NN/fellow coverage and 24-h fellow coverage were associated with higher odds of infants receiving DR chest compressions or epinephrine compared to 24-h NN coverage (adjusted odds ratio [AOR] 4.72, 95% CI 2.12-10.6 and AOR 3.33, 95% CI 1.44-7.70, respectively) (Table 2). 24-h fellow coverage was associated with higher odds of normothermia (36.5°C-37.2°C) on admission (AOR 2.26, 95% CI 1.51-3.37) compared to 24-h NN coverage (Table 2). Rates of mortality or major morbidity did not differ significantly among the three groups: NN, 63% (249/395); fellow, 64% (1092/1700); no NN/fellow, 70% (266/381). Compared to 24-h NN coverage, 24-h fellow coverage was associated with lower odds of mortality (AOR 0.62, 95% CI, 0.43-0.88) (Table 2). Conclusion 24-h in-house NN coverage was associated with lower rates of DR chest compressions or epinephrine use; however, it was not associated with death and/or major morbidity. These results are from a survey linked cohort, and data on the actual presence of individuals in NICU/resuscitation is unknown. Future prospective research on care providers present in the NICU, and its impact on outcomes, is needed.

scholarly journals Temporal trends of in utero and early postnatal transfer of extremely preterm infants between 2011 and 2016: a UK population study

2021 ◽  
pp. fetalneonatal-2021-322195
Author(s):  
Lara Shipley ◽  
Gillian Hyliger ◽  
Don Sharkey
Keyword(s):  
Preterm Infants ◽  
Temporal Trends ◽  
In Utero ◽  
Adverse Outcomes ◽  
Research Database ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Hospital Transfer ◽  
The Uk ◽  
National Trends

ObjectiveEarly postnatal transfer (PNT) of extremely preterm infants is associated with adverse outcomes compared with in utero transfer (IUT). We aimed to explore recent national trends of IUT and early PNT.DesignObservational cohort study using the National Neonatal Research Database.SettingNeonatal units in England, Scotland and Wales.PatientsExtremely preterm infants 23+0–27+6 weeks’ gestation admitted for neonatal care from 2011 to 2016.Main outcomeThe incidence of IUT or PNT within 72 hours of life. Secondary outcomes included mortality, hospital transfer level between centres and temporal changes across two equal epochs, 2011–2013 (epoch 1 (Ep1)) and 2014–2016 (epoch 2 (Ep2)).Results14 719 infants were included (Ep1=7363 and Ep2=7256); 4005 (27%) underwent IUT; and 3042 (20.7%) had PNT. IUTs decreased significantly between epochs from 28.3% (Ep1=2089) to 26.0% (Ep2=1916) (OR 0.90, 95% CI 0.84 to 0.97, p<0.01). Conversely, PNTs increased from 19.8% (Ep1=1416) to 21.5% (Ep2=1581) (OR 1.11, 95% CI 1.02 to 1.20, p=0.01). PNTs between intensive care centres increased from 8.1% (Ep1=119) to 10.2% (Ep2=161, p=0.05). Mortality decreased from 21.6% (Ep1=1592) to 19.3% (Ep2=1421) (OR 0.90, 95% CI 0.83 to 0.97, p=0.01). Survival to 90 days of age was significantly lower in infants undergoing PNT compared with IUT (HR 1.31, 95% CI 1.18 to 1.46), with the greatest differences observed in infants <25 weeks’ gestational age.ConclusionIn the UK, IUT of extremely preterm infants has significantly decreased over the study period with a parallel increase in early PNT. Strategies to reverse these trends, improve IUT pathways and optimise antenatal steroid use could significantly improve survival and reduce brain injury for these high-risk infants.

scholarly journals Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1871 ◽  
Author(s):  
Daan R.M.G. Ophelders ◽  
Ruth Gussenhoven ◽  
Luise Klein ◽  
Reint K. Jellema ◽  
Rob J.J. Westerlaken ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Brain Injury ◽  
Preterm Infants ◽  
Critical Role ◽  
Perinatal Brain Injury ◽  
Preclinical Research ◽  
Mortality And Morbidity ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Hypoxia Ischemia

With a worldwide incidence of 15 million cases, preterm birth is a major contributor to neonatal mortality and morbidity, and concomitant social and economic burden Preterm infants are predisposed to life-long neurological disorders due to the immaturity of the brain. The risks are inversely proportional to maturity at birth. In the majority of extremely preterm infants (<28 weeks’ gestation), perinatal brain injury is associated with exposure to multiple inflammatory perinatal triggers that include antenatal infection (i.e., chorioamnionitis), hypoxia-ischemia, and various postnatal injurious triggers (i.e., oxidative stress, sepsis, mechanical ventilation, hemodynamic instability). These perinatal insults cause a self-perpetuating cascade of peripheral and cerebral inflammation that plays a critical role in the etiology of diffuse white and grey matter injuries that underlies a spectrum of connectivity deficits in survivors from extremely preterm birth. This review focuses on chorioamnionitis and hypoxia-ischemia, which are two important antenatal risk factors for preterm brain injury, and highlights the latest insights on its pathophysiology, potential treatment, and future perspectives to narrow the translational gap between preclinical research and clinical applications.

scholarly journals Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3

2021 ◽  
pp. 1-15
Author(s):  
Magnus Gram ◽  
Claes Ekström ◽  
Bo Holmqvist ◽  
Galen Carey ◽  
Xiaoyang Wang ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Growth Factor ◽  
Choroid Plexus ◽  
Preterm Infants ◽  
Binding Protein ◽  
Serum Levels ◽  
In Utero ◽  
Insulin Like Growth Factor ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.

Improving Feeding Outcomes in the NICU: Moving From Volume-Driven to Infant-Driven Feeding

2010 ◽  
Vol 19 (3) ◽  
pp. 68-74 ◽  
Author(s):  
Catherine S. Shaker
Keyword(s):  
Intensive Care Unit ◽  
Dynamic Systems ◽  
Neonatal Intensive Care ◽  
Well Being ◽  
Dynamic Systems Theory ◽  
Feeding Problems ◽  
Care Giving ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Current research on feeding outcomes after discharge from the neonatal intensive care unit (NICU) suggests a need to critically look at the early underpinnings of persistent feeding problems in extremely preterm infants. Concepts of dynamic systems theory and sensitive care-giving are used to describe the specialized needs of this fragile population related to the emergence of safe and successful feeding and swallowing. Focusing on the infant as a co-regulatory partner and embracing a framework of an infant-driven, versus volume-driven, feeding approach are highlighted as best supporting the preterm infant's developmental strivings and long-term well-being.

Life expectancy of extremely preterm infants

2007 ◽  
Vol 148 (48) ◽  
pp. 2279-2284 ◽  
Author(s):  
Gabriella Vida ◽  
Ilona Sárkány ◽  
Simone Funke ◽  
Judit Gyarmati ◽  
Judit Storcz ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Preterm Infants ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Optimális esetben a 24–28. gesztációs hét közötti, igen éretlen újszülöttek olyan szülészeti intézményben születnek, ahol neonatalis intenzív centrum működik, így mind az akut, mind a hosszú távú ellátásukat magas színvonalon biztosítják. A PTE OEKK ÁOK Szülészeti és Nőgyógyászati Klinikán 2000. január 1. és 2004. december 31. között 7499 újszülött született. A koraszülési frekvencia 20% (1499/7499), ezen belül az extrém alacsony gesztációs korúak aránya (≦28. gesztációs hét) 18% (272/1499), míg a 25. gesztációs hét alattiaké 3,2% (48/1499) volt. A túlélés a gesztációs hetek emelkedésével fokozatosan javul. Az életben maradt koraszülöttek későbbi életkilátásai és társadalmi beilleszkedése függ az olyan maradandó károsodásoktól, mint a látáscsökkenés, halláskárosodás, somatomentalis fejlődés zavarai, krónikus tüdőbetegség. A klinikán vizsgált alacsony gesztációs korú csoportban az összes fogyatékkal élő betegek aránya 15,3%. Döntő többségük a 25. gesztációs hétnél korábban született koraszülöttek közül kerül ki. A 26. gesztációs héttől a koraszülöttek több mint fele tartós károsodás nélkül éli túl az extrém éretlenség társuló problémáit. Megállapították, hogy a korai koponya-ultrahangvizsgálattal, szemészeti szűréssel, otoacusticus emissio mérésével jól prognosztizálhatók a maradandó károsodások, így lehetővé válik a korai kezelés.

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