Center for Perinatal Research

Sun City Center, United States

Center for Perinatal Research

Sun City Center, United States
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Padula M.A.,Children's Hospital of Philadelphia | Grover T.R.,Aurora University | Brozanski B.,University of Pittsburgh | Zaniletti I.,Childrens Hospital Association | And 9 more authors.
Journal of Perinatology | Year: 2013

Objective:To characterize the treatments and short-term outcomes in infants with severe bronchopulmonary dysplasia (sBPD) referred to regional neonatal intensive care units.Study Design:Infants born <32 weeks' gestation with sBPD were identified using the Children's Hospital Neonatal Database. Descriptive outcomes are reported.Result:A total of 867 patients were eligible. On average, infants were born at 26 weeks' gestation and referred 43 days after birth. Infants frequently experienced lung injury (pneumonia: 24.1%; air leak: 9%) and received systemic corticosteroids (61%) and mechanical ventilation (median duration 37 days). Although 91% survived to discharge, the mean post-menstrual age was 47 weeks. Ongoing care such as supplemental oxygen (66%) and tracheostomy (5%) were frequently needed.Conclusion:Referred infants with sBPD sustain multiple insults to lung function and development. Because affected infants have no proven, safe or efficacious therapy and endure an exceptional burden of care even after referral, urgent work is required to observe and improve their outcomes. © 2013 Nature America, Inc. All rights reserved.

News Article | November 10, 2016

The discovery that small calcium deposits in fetal membranes may lead to a mother's water breaking prematurely suggests that dietary or other interventions could prevent those preterm births. Most spontaneous preterm births do not have causes that are easy to identify. Physicians frequently have not known why uterine contractions begin weeks earlier than they should, in one major form of preterm birth; or why a mother's water breaks well before the fetus is fully developed, in another major form. One in 10 babies is born preterm - before 37 weeks of pregnancy - and may face long-term health problems as a result. Learning why these births occur is critical to preventing them. And a new study from Nationwide Children's Hospital may have solved part of this mystery. Researchers found that in preterm, premature rupture of the fetal membranes - that is, water breaking significantly early- the amniotic sac contains calcium deposits and early markers of bone formation. The membranes, then, are less elastic and more prone to breaking. "We do see calcium deposits in full term births as well, which is probably part of the normal breakdown of the membranes at the appropriate time," says Irina Buhimschi, MD, senior author of the study and director of the Center for Perinatal Research at The Research Institute at Nationwide Children's. "The membranes are supposed to rupture when labor is underway. However, these calcium deposits are too many and too early." The study, published today in Science Translational Medicine, also demonstrates how the deposits occur. Many human body fluids, including saliva and blood, can produce calciprotein particles. When those particles deposit in soft tissues outside of the skeleton, they can lead to harmful calcification. Calciprotein particles have been implicated in kidney stones, atherosclerosis and aneurism rupture. A protein called fetuin-A helps prevent those particles from depositing where they shouldn't. This study shows for the first time that amniotic fluid can also produce calciprotein particles. In cases of preterm premature rupture of membranes, the amniotic fluid has decreased concentrations of fetuin-A, resulting in a decreased ability to stop the particles from depositing in the amniotic sac. When researchers exposed fetal membrane cells to calciprotein particles, the particles led the fetal membrane tissue to begin creating osteoblasts, the precursors of bone. These findings suggest that it may be possible to identify pregnancies at greater risk for premature preterm rupture of membranes, says Dr. Buhimschi, who is also a professor of Pediatrics and Obstetrics/Gynecology at The Ohio State University College of Medicine. They also suggest possible interventions to prevent these kinds of preterm births. "We need to see if there are women who lack the capacity to prevent these early calcifications," says Dr. Buhimschi, who began her work linking prematurity and calcification at the Yale University School of Medicine. "I also believe strongly that there are dietary measures that would improve the intra-amniotic environment for these women. We know that dietary interventions are critical in atherosclerosis and other disease processes that involve calciprotein particles. We just have never considered it in preterm premature rupture of membranes before." Shook L, Buhimschi C, Dulay A, McCarthy M, Hardy J, Buniak C, Zhao G, Buhimschi I. Calciprotein Particles as Potential Etiologic Agents of Idiopathic Preterm Birth. Science Translational Medicine. 2016 Nov 9 [Epub ahead of print]

Luce W.A.,Ohio State University | Luce W.A.,Heart Center | Luce W.A.,Center for Perinatal Research | Luce W.A.,Nationwide Childrens Hospital | And 14 more authors.
Pediatric Critical Care Medicine | Year: 2011

Objective: To investigate the prevalence of necrotizing enterocolitis (NEC) in neonates undergoing the Stage I hybrid procedure for palliation of complex congenital heart disease (CHD). Neonates undergoing the Norwood surgery for hypoplastic left-heart syndrome have the highest risk for NEC of all CHD patients. The hybrid procedure is another palliative option for hypoplastic left-heart syndrome, but NEC in neonates undergoing this procedure has not been reported. Design: Retrospective chart review of 73 neonates who underwent the hybrid procedure for palliation of complex CHD. Demographic, perinatal, perioperative, clinical, and procedural data were collected. NEC was defined as modified Bell's Stage II and above. Setting: The cardiothoracic and neonatal intensive care units in a large free-standing children's hospital. Patients: All neonates who underwent the hybrid Stage I procedure for the palliation of complex CHD from April 2002 through April 2008. Measurements and Main Results: Seventy-three neonates were reviewed and 11.0% (eight of 73) developed NEC. Of the patients with NEC, 37.5% (three of eight) died and two patients required abdominal surgery. Earlier gestational age (<37 wks), lower maximum dose of prostaglandin infusion, and unexpected readmission to the intensive care unit were statistically associated with NEC (p = .009, 0.02, and 0.04, respectively). No other demographic, perinatal, perioperative, clinical, or procedural variables were associated with the development of NEC in this patient population, including enteral feeding regimens, umbilical artery catheters, inotrope use, and average oxygen saturation and diastolic blood pressure. Conclusions: The prevalence of NEC in patients undergoing the hybrid procedure is comparable to that reported for neonates undergoing the Norwood procedure. Earlier gestational age is a significant risk factor for NEC in patients who undergo the hybrid Stage I procedure. Multidisciplinary approaches to better understand abdominal complications and to develop feeding regimens in neonates undergoing the hybrid approach to complex CHD are needed to improve outcomes and decrease morbidities. Copyright © 2011 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

Heathcock J.C.,Ohio State University | Heathcock J.C.,Center for Perinatal Research | Baranet K.,Nationwide Childrens Hospital | Ferrante R.,Nationwide Childrens Hospital | Hendershot S.,Nationwide Childrens Hospital
Pediatric Physical Therapy | Year: 2015

To describe a daily physical therapy (PT) intervention program and outcomes for 2 young children with spastic quadriplegia, Gross Motor Function Classification System (GMFCS) level V, and to evaluate the feasibility of using a daily program in an urban children's hospital outpatient setting. Summary of Key Points: Two young children, GMFCS level V, received 2 hours of PT intervention based on motor learning principles 5 days a week for 4 consecutive weeks. Gross Motor Functional Measure (GMFM-66, GMFM-88) and the Bayley Scales of Infant Development, Third Edition, were used as pre-and postoutcome measures. The daily, high intensity intervention was well tolerated. Improvements in motor function, language, and cognitive skills were found. Statement of Conclusion: A daily PT program appears feasible and may improve overall development in young children with cerebral palsy in GMFCS level V. © 2015 Wolters Kluwer Health, Inc.

James I.A.O.,Ohio State University | James I.A.O.,Center for Perinatal Research | Chen C.-L.,Ohio State University | Chen C.-L.,Center for Perinatal Research | And 6 more authors.
Journal of Surgical Research | Year: 2010

Background: Acute respiratory distress syndrome continues to be a major source of morbidity and mortality in critically-ill patients. Heparin binding EGF-like growth factor (HB-EGF) is a biologically active protein that acts as an intestinal cytoprotective agent. We have previously demonstrated that HB-EGF protects the intestines from injury in several different animal models of intestinal injury. In the current study, we investigated the ability of HB-EGF to protect the lungs from remote organ injury after intestinal ischemia/reperfusion (I/R). Methods: Mice were randomly assigned to one of the following groups: (1) sham-operated; (2) sham+HB-EGF (1200 μg/kg in 0.6 mL administered by intra-luminal injection at the jejuno-ileal junction immediately after identification of the superior mesenteric artery); (3) superior mesenteric artery occlusion for 45 min followed by reperfusion for 6 h (I/R); or (4) I/R+HB-EGF (1200 μg/kg in 0.6 mL) administered 15 min after vascular occlusion. The severity of acute lung injury was determined by histology, morphometric analysis and invasive pulmonary function testing. Animal survival was evaluated using Kaplan-Meier analysis. Results: Mice subjected to intestinal I/R injury showed histologic and functional evidence of acute lung injury and decreased survival compared with sham-operated animals. Compared with mice treated with HB-EGF (I/R+HB-EGF), the I/R group had more severe acute lung injury, and decreased survival. Conclusion: Our results demonstrate that HB-EGF reduces the severity of acute lung injury after intestinal I/R in mice. These data demonstrate that HB-EGF may be a potential novel systemic anti-inflammatory agent for the prevention of the systemic inflammatory response syndrome (SIRS) after intestinal injury. © 2010 Elsevier Inc. All rights reserved.

Rose M.J.,Nationwide Childrens Hospital | Stenger M.R.,Center for Perinatal Research | Joshi M.S.,Nationwide Childrens Hospital | Welty S.E.,Center for Perinatal Research | And 2 more authors.
Pediatric Research | Year: 2010

Chronic lung injury in the neonate is termed bronchopulmonary dysplasia (BPD). These patients generally require supplemental oxygen therapy, and hyperoxia has been implicated in the pathogenesis of BPD. The concomitant use of oxygen and inhaled NO (iNO) may result in the generation of reactive nitrogen species or may have an anti-inflammatory effect in the neonatal lung. We tested the hypothesis that exposure to >95% O2 in neonatal mice would increase trafficking of leukocytes into the lung and that the addition of iNO to >95% O2 would decrease this leukocyte trafficking. Hyperoxia resulted in fewer alveoli, increased presence of neutrophils and macrophages, and decreased number of mast cells within the lung parenchyma. Adding iNO to hyperoxia prevented the hyperoxia-induced changes and resulted in the numbers of alveoli, neutrophils, macrophages, and mast cells approximating those found in controls (room air exposure). Intercellular adhesion molecule (ICAM) and monocyte chemotactic protein-1 (MCP-1), two factors responsible for leukocyte recruitment, were up-regulated by hyperoxic exposure, but the addition of iNO to the hyperoxic exposure prevented the hyperoxia-induced up-regulation of ICAM and MCP-1. These data demonstrate that iNO alters the hyperoxia-induced recruitment of leukocytes into the lung. Copyright © 2010 International Pediatric Research Foundation, Inc.

Gwathmey T.M.,Wake forest University | Pendergrass K.D.,Wake forest University | Reid S.D.,Center for Perinatal Research | Rose J.C.,Wake forest University | And 2 more authors.
Hypertension | Year: 2010

The angiotensin (Ang) type 1 receptor (AT1R) is highly expressed on renal nuclei and stimulates reactive oxygen species (ROS). It is not known whether other functional components of the Ang system regulate the nuclear Ang II-AT1R ROS pathway. Therefore, we examined the expression of Ang receptors in nuclei isolated from the kidneys of young adult (1.5 years) and older adult (3.0 to 5.0 years) sheep. Binding studies in renal nuclei revealed the AT2R as the predominant receptor subtype (≈80%) in young sheep, with the Ang-(1-7) (AT7R; Mas protein) and AT1R antagonists competing for the remaining sites. Conversely, in older sheep, the AT1R accounted for ≈85% of nuclear sites, whereas the Ang type 2 receptor and AT7R subtypes comprise ≈20% of remaining sites. Ang II increased nuclear ROS to a greater extent in older (97±22%; n=6) versus young animals (7±2%; P=0.01; n=4), and this was abolished by an AT1R antagonist. The AT7R antagonist D-Ala-Ang-(1-7) increased ROS formation to Ang II by ≈-fold (174±5% versus 97±22%; P<0.05) in older adults. Immunoblots of renal nuclei revealed protein bands for the AT7R and Ang-converting enzyme 2 (ACE2), which metabolizes Ang II to Ang-(1-7). The ACE2 inhibitor MLN4760 also exacerbated the Ang II-dependent formation of ROS (156±15%) and abolished the generation of Ang-(1-7) from Ang II. We conclude that an ACE2-Ang-(1-7)-AT7R pathway modulates Ang II-dependent ROS formation within the nucleus, providing a unique protective mechanism against oxidative stress and cell damage. © 2010 American Heart Association, Inc.

Jadcherla S.R.,Ohio State University | Jadcherla S.R.,Center for Perinatal Research | Chan C.Y.,Center for Perinatal Research | Moore R.,Center for Perinatal Research | And 2 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2013

We aimed to define the sensorimotor characteristics of aero-digestive reflexes evoked upon midesophageal provocations in neuropathology infants. Provocative esophageal motility testing was performed in 20 neuropathology infants and 10 controls at 42.3 ± 0.6 and 38.9 ± 0.9 wk postmenstrual age. Data from 1,073 infusions were examined for the sensory thresholds, response frequencies, response magnitude of upper esophageal sphincter (UES) contractile reflexes, lower esophageal sphincter (LES) relaxation reflexes, and peristaltic reflexes using mixed statistical models. Threshold volumes for air and liquid in neuropathology and control infants were similar for all reflexes. Graded air- and liquid volume-dependent UES contractile reflex, LES relaxation reflex, and peristaltic reflex frequency recruitment were present in neuropathology and control subjects for the media (P < 0.0001) and the reflexes (P < 0.0001). In neuropathology infants (vs. controls), UES contractile magnitude is higher (P < 0.0001); LES relaxation reflex occurred earlier (P = 0.008); LES nadir duration lasted longer (P = 0.006); secondary peristalsis is the chief method of esophageal clearance (P < 0.0001); pharyngeal swallows and deglutition apneas are less frequent (P = 0.001); proximal, midesophageal waveform magnitudes and duration are exaggerated (P < 0.008). UES contractile reflex was longer with liquid than air in both groups (P = 0.03). We concluded that 1) perception to midesophageal provocation remains preserved in neuropathology neonates; 2) sustained and exaggerated myogenic response from afferent activation is evident by increased excitatory efferent outputs to the UES and esophageal body and increased inhibitory efferent outputs to the LES; 3) dysfunctional regulation of pharyngeal swallowing and infrequent deglutition responses indicate the possibility of impaired descending modulation and central malfunctions of brainstem and vagal nuclei.© 2013 the American Physiological Society.

Natarajan G.,Wayne State University | Johnson Y.R.,Baylor College of Medicine | Brozanski B.,University of Pittsburgh | Farrow K.N.,Northwestern University | And 10 more authors.
American Journal of Perinatology | Year: 2014

Objectives To characterize postnatal growth failure (PGF), defined as weight < 10th percentile for postmenstrual age (PMA) in preterm (≤ 27 weeks' gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others. Study Design Retrospective review of data from the multicenter Children's Hospital Neonatal Database (CHND). Results Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks' PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to > 70% and parenteral nutrition to a third of infants between 36 and 44 weeks' PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p < 0.01). Conclusions Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population. Copyright © 2014 by Thieme Medical.

PubMed | Quality Improvement Services and., Center for Perinatal Research and Nationwide Childrens Hospital
Type: | Journal: Pediatrics | Year: 2017

Ensuring safe human milk in the NICU is a complex process with many potential points for error, of which one of the most serious is administration of the wrong milk to the wrong infant. Our objective was to describe a quality improvement initiative that was associated with a reduction in human milk administration errors identified over a 6-year period in a typical, large NICU setting.We employed a quasi-experimental time series quality improvement initiative by using tools from the model for improvement, Six Sigma methodology, and evidence-based interventions. Scanned errors were identified from the human milk barcode medication administration system. Scanned errors of interest were wrong-milk-to-wrong-infant, expired-milk, or preparation errors. The scanned error rate and the impact of additional improvement interventions from 2009 to 2015 were monitored by using statistical process control charts.From 2009 to 2015, the total number of errors scanned declined from 97.1 per 1000 bottles to 10.8. Specifically, the number of expired milk error scans declined from 84.0 per 1000 bottles to 8.9. The number of preparation errors (4.8 per 1000 bottles to 2.2) and wrong-milk-to-wrong-infant errors scanned (8.3 per 1000 bottles to 2.0) also declined.By reducing the number of errors scanned, the number of opportunities for errors also decreased. Interventions that likely had the greatest impact on reducing the number of scanned errors included installation of bedside (versus centralized) scanners and dedicated staff to handle milk.

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