Manuel Alvarez

Hackensack Meridian Health

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Abdulla Al‐Khan

Hackensack University Medical Center

Alan H. Jobe

Cincinnati Children's Hospital Medical Center

Suhas G. Kallapur

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Claire Chougnet

University of Cincinnati Medical Center

Jesus Alvarez‐Perez

Health Net

Stacy Zamudio

Rutgers, The State University of New Jersey

Christine L. Knox

Centers for Disease Control and Prevention

Amanda Prince

Vedantra Pharmaceuticals (United States)

Nicholas P. Illsley

Rutgers, The State University of New Jersey

Paranthaman S. Kannan

Cincinnati Children's Hospital Medical Center

Cooperative Institutions

Cincinnati Children's Hospital Medical Center

Wright State University

Christiana Care Health System

Coombe Women & Infants University Hospital

Royal College of Surgeons in Ireland

Medical University of South Carolina

Hackensack University Medical Center

University of Miami

Duke University

University of North Carolina at Chapel Hill

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Brain Natriuretic Peptide in Term Pregnancy

Reproductive Sciences (2012)

Ladin A. Yurteri-Kaplan Shelley Saber Stacy Zamudio Deepak Srinivasan Themba Nyirenda

Brain natriuretic peptide

Interquartile range

Atrial natriuretic peptide

10.1177/1933719111426598

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Citations (17)

Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants

Archives of Disease in Childhood Fetal & Neonatal (2016)

Tate Gisslen Manuel Alvarez Casey Wells Man-Ting Soo Donna S. Lambers

Objective

To determine whether exposure to acute chorioamnionitis and fetal inflammation caused short-term adverse outcomes.

Design

This is a prospective observational study: subjects were mothers delivering at 32–36 weeks gestation and their preterm infants at a large urban tertiary level III perinatal unit (N=477 infants). Placentae and fetal membranes were scored for acute histological chorioamnionitis based on the Redline criteria. Fetal inflammation was characterised by histological diagnosis of funisitis (umbilical cord inflammation), increased cord blood cytokines measured by ELISA, and activation of the inflammatory cells infiltrating the placenta and fetal membranes measured by immunohistology. Maternal and infant data were collected.

Results

Twenty-four per cent of 32–36-week infants were exposed to histological chorioamnionitis and 6.9% had funisitis. Immunostaining for leucocyte subsets showed selective infiltration of the placenta and fetal membranes with activated neutrophils and macrophages with chorioamnionitis. Interleukin (IL) 6, IL-8 and granulocyte colony-stimulating factor were selectively increased in the cord blood of preterm infants with funisitis. Compared with infants without chorioamnionitis, funisitis was associated with increased ventilation support during resuscitation (43.8% vs 15.4%) and more respiratory distress syndrome postnatally (27.3% vs 10.2%) in univariate analysis. However, these associations disappeared after adjusting for prematurity.

Conclusions

Despite fetal exposure to funisitis, increased cord blood cytokines and activated placental inflammatory cells, we could not demonstrate neonatal morbidity specifically attributable to fetal inflammation after adjusting for gestational age in moderate and late preterm infants.

Chorioamnionitis

Cord blood

10.1136/archdischild-2015-308518

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Citations (16)

A novel method for laparoscopic abdominal cerclage utilizing minimally invasive hydrodissection: a case report.

PubMed (2007)

Ramzi Aboujaoude Paul Maloof Manuel Alvarez Abdulla Al Khan

Cervical incompetence can lead to the inability to sustain an intrauterine pregnancy and may account for a substantial portion of second-trimester losses. Placement of a transvaginal cerclage has been shown to decrease morbidity in a substantial number of such cases. In patients lacking sufficient cervical tissue, a cerclage may be placed by a transabdominal approach. This procedure carries risks of significant morbidity to the maternal-fetal unit if done by laparotomy.A 22-year-old gravida at 13 weeks' gestation with a past history significant for cervical incompetence and absence of cervical tissue underwent placement of an abdominal cerclage. We utilized laparoscopic operative techniques and employed hydrodissection to decrease manipulation and bleeding around the gravid uterus.A laparoscopic approach to cerclage in patients diagnosed with cervical incompetence can be performed with minimal risks to the gravid uterus.

Cervical insufficiency

Cervical cerclage

Products of conception

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Citations (7)

Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants

Faculty of Health; Institute of Health and Biomedical Innovation (2016)

Tate Gisslen Manuel Alvarez Casey Wells Man-Ting Soo Donna S. Lambers

Objective To determine whether exposure to acute chorioamnionitis and fetal inflammation caused short-term adverse outcomes. Design This is a prospective observational study: subjects were mothers delivering at 32–36 weeks gestation and their preterm infants at a large urban tertiary level III perinatal unit (N=477 infants). Placentae and fetal membranes were scored for acute histological chorioamnionitis based on the Redline criteria. Fetal inflammation was characterised by histological diagnosis of funisitis (umbilical cord inflammation), increased cord blood cytokines measured by ELISA, and activation of the inflammatory cells infiltrating the placenta and fetal membranes measured by immunohistology. Maternal and infant data were collected. Results Twenty-four per cent of 32–36-week infants were exposed to histological chorioamnionitis and 6.9% had funisitis. Immunostaining for leucocyte subsets showed selective infiltration of the placenta and fetal membranes with activated neutrophils and macrophages with chorioamnionitis. Interleukin (IL) 6, IL-8 and granulocyte colony-stimulating factor were selectively increased in the cord blood of preterm infants with funisitis. Compared with infants without chorioamnionitis, funisitis was associated with increased ventilation support during resuscitation (43.8% vs 15.4%) and more respiratory distress syndrome postnatally (27.3% vs 10.2%) in univariate analysis. However, these associations disappeared after adjusting for prematurity. Conclusions Despite fetal exposure to funisitis, increased cord blood cytokines and activated placental inflammatory cells, we could not demonstrate neonatal morbidity specifically attributable to fetal inflammation after adjusting for gestational age in moderate and late preterm infants.

Chorioamnionitis

Cord blood

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Scleroderma Renal Crisis <i>Sine </i>Scleroderma

The Nephron journals/Nephron journals (2001)

J.-J. Canet J. Bosch Castañé Manuel Alvarez Juan-Manuel Nava Joan Bayó Llibre

Scleroderma (fungus)

10.1159/000046327

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Citations (10)

Functional Capacity of the Glucocorticoid Receptor in Pre-term Neonates

PEDIATRICS (2018)

Adaora Madubuko A.K. Kashyap Abdulla Al‐Khan Jesus Alvarez‐Perez Manuel Alvarez

10.1542/peds.142.1ma2.192

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Management of missed abortion in a patient with congenital uterine anomalies

Archives of Gynecology and Obstetrics (2006)

Ramzi Aboujaoude Jesús Román Martínez Álvarez Manuel Alvarez Abdulla Al‐Khan

Missed abortion

Uterine rupture

10.1007/s00404-006-0195-2

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Citations (2)

Intra-Amniotic IL-1β Induces Fetal Inflammation in Rhesus Monkeys and Alters the Regulatory T Cell/IL-17 Balance

The Journal of Immunology (2013)

Suhas G. Kallapur Pietro Presicce Paranthaman Senthamaraikannan Manuel Alvarez Alice F. Tarantal

Very low birth weight preterm newborns are susceptible to the development of debilitating inflammatory diseases, many of which are associated with chorioamnionitis. To define the effects of chorioamnionitis on the fetal immune system, IL-1β was administered intra-amniotically at ~80% gestation in rhesus monkeys. IL-1β caused histological chorioamnionitis, as well as lung inflammation (infiltration of neutrophils or monocytes in the fetal airways). There were large increases in multiple proinflammatory cytokine mRNAs in the lungs at 24 h postadministration, which remained elevated relative to controls at 72 h. Intra-amniotic IL-1β also induced the sustained expression of the surfactant proteins in the lungs. Importantly, IL-1β significantly altered the balance between inflammatory and regulatory T cells. Twenty-four hours after IL-1β injection, the frequency of CD3(+)CD4(+)FOXP3(+) T cells was decreased in lymphoid organs. In contrast, IL-17A-producing cells (CD3(+)CD4(+), CD3(+)CD4(-), and CD3(-)CD4(-) subsets) were increased in lymphoid organs. The frequency of IFN-γ-expressing cells did not change. In this model of a single exposure to an inflammatory trigger, CD3(+)CD4(+)FOXP3(+) cells rebounded quickly, and their frequency was increased at 72 h compared with controls. IL-17 expression was also transient. Interestingly, the T cell profile alteration was confined to the lymphoid organs and not to circulating fetal T cells. Together, these results suggest that the chorioamnionitis-induced IL-1/IL-17 axis is involved in the severe inflammation that can develop in preterm newborns. Boosting regulatory T cells and/or controlling IL-17 may provide a means to ameliorate these abnormalities.

10.4049/jimmunol.1300270

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Citations (69)

Perinatal outcomes in critically ill pregnant women with coronavirus disease 2019

American Journal of Obstetrics & Gynecology MFM (2020)

Matthew P. Romagano Kerly Guerrero Nicole T. Spillane Emre Kayaalp Scott W. Smilen

Coronavirus

2019-20 coronavirus outbreak

Pandemic

10.1016/j.ajogmf.2020.100151

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Citations (22)

Neutrophil Recruitment and Activation in Decidua with Intra-Amniotic IL-1beta in the Preterm Rhesus Macaque1

Biology of Reproduction (2014)

Pietro Presicce Paranthaman Senthamaraikannan Manuel Alvarez Cesar M. Rueda Monica Cappelletti

Chorioamnionitis, an infection/inflammation of the fetomaternal membranes, is frequently associated with preterm delivery. The mechanisms of inflammation in chorioamnionitis are poorly understood. We hypothesized that neutrophils recruited to the decidua would be the major producers of proinflammatory cytokines. We injected intra-amniotic (IA) interleukin 1beta (IL-1beta) at ∼80% gestation in rhesus macaque monkeys, Macaca mulatta, delivered the fetuses surgically 24 h or 72 h after IA injections, and investigated the role of immune cells in the chorion-amnion decidua. IA IL-1beta induced a robust infiltration of neutrophils and significant increases of proinflammatory cytokines in the chorioamnion decidua at 24 h after exposure, with a subsequent decrease at 72 h. Neutrophils in the decidua were the major source of tumor necrosis factor alpha (TNFalpha) and IL-8. Interestingly, IA IL-1beta also induced a significant increase in anti-inflammatory indoleamine 2,3-dioxygenase (IDO) expression in the decidua neutrophils. The frequency of regulatory T cells (Tregs) and FOXP3 mRNA expression in the decidua did not change after IA IL-1beta injection. Collectively, our data demonstrate that in this model of sterile chorioamnionitis, the decidua neutrophils cause the inflammation in the gestational tissues but may also act as regulators to dampen the inflammation. These results help to understand the contribution of neutrophils to the pathogenesis of chorioamnionitis-induced preterm labor.

Decidua

Chorioamnionitis

Proinflammatory cytokine

Amnion

10.1095/biolreprod.114.124420

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Citations (62)