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Almudares F, Gandhi B, Davies J, Couroucli X, Villafranco N, Varghese NP, Guaman MC, Guillory C, Shivanna B. Oxygen Saturation Targeting in the Neonatal Intensive Care Unit. J Clin Med 2025; 14:3975. [PMID: 40507737 PMCID: PMC12155839 DOI: 10.3390/jcm14113975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2025] [Revised: 05/22/2025] [Accepted: 05/29/2025] [Indexed: 06/16/2025] Open
Abstract
Oxygen (O2) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O2) and hyperoxia (excess tissue O2), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O2 saturation targets and therapeutic titration. Most current neonatal O2 targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles of O2 in development, its delivery and consumption, approaches to O2 saturation monitoring, and therapeutic targeting in neonates under both normal and pathological conditions. We also highlight key knowledge gaps and propose directions for future research on neonatal O2 saturation targeting.
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Affiliation(s)
- Faeq Almudares
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
| | - Bheru Gandhi
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
| | - Jonathan Davies
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
| | - Xanthi Couroucli
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
| | - Natalie Villafranco
- Division of Pulmonology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (N.V.); (N.P.V.)
| | - Nidhy Paulose Varghese
- Division of Pulmonology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (N.V.); (N.P.V.)
| | - Milenka Cuevas Guaman
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
| | - Charleta Guillory
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
| | - Binoy Shivanna
- Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; (F.A.); (B.G.); (J.D.); (X.C.); (M.C.G.); (C.G.)
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Mercer J, Saether E, King T, Maul H, Kennedy HP, Erickson-Owens D, Andersson O, Rabe H. How Delayed Cord Clamping Saves Newborn Lives. CHILDREN (BASEL, SWITZERLAND) 2025; 12:585. [PMID: 40426764 PMCID: PMC12110096 DOI: 10.3390/children12050585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 04/23/2025] [Accepted: 04/28/2025] [Indexed: 05/29/2025]
Abstract
Interest in the subject of umbilical cord clamping is long-standing. New evidence reveals that placental transfusion, facilitated by delayed cord clamping (DCC), reduces death and need for blood transfusions for preterm infants without evidence of harm. Even a brief delay in clamping the cord shows improved survival and well-being, but waiting at least two minutes is even better. We propose that three major benefits from DCC contribute to reduced mortality of preterm infants: (1) benefits from the components of blood; (2) assistance from the continued circulation of blood; and (3) the essential mechanical interactions that result from the enhanced volume of blood. The enhanced blood volume generates mechanical forces within the microcirculation that support the newborn's metabolic and cardiovascular stability and secure short- and long-term organ health. Several unique processes prime preterm and term newborns to receive the full placental transfusion, not to be misinterpreted as extra blood or over-transfusion. Disrupting cord circulation before the newborn's lung capillary bed has been fully recruited and the lungs can replace the placenta as a respiratory, gas-exchanging organ may be harmful. Early cord clamping also denies the newborn a full quota of iron-rich red blood cells as well as valuable stem cells for regeneration, repair, and seeding of a strong immune system. We propose that delayed cord clamping and intact-cord stabilization have the potential to save lives by protecting many neonates from hypovolemia, inflammation, and ischemia.
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Affiliation(s)
- Judith Mercer
- College of Nursing, University of Rhode Island, Kingston, RI 02881, USA;
| | | | - Tekoa King
- School of Nursing, University of California, San Francisco, CA 94143, USA;
| | - Holger Maul
- Department of Obstetrics and Gynecology of the Asklepios Kliniken Barmbek, Wandsbek and Nord-Heidberg, 22039 Hamburg, Germany;
| | | | | | - Ola Andersson
- Department of Neonatology, Skåne University Hospital, 22185 Malmo/Lund, Sweden;
- Department of Clinical Sciences, Pediatrics/Neonatology, Lund University, 22362 Lund, Sweden
| | - Heike Rabe
- Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9QG, UK;
- Department of Neonatology, University Hospitals Sussex NHS Foundation Trust, Royal Sussex County Hospital, Brighton BN2 5BE, UK
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Spencer BL, Fallon BP, McLeod JS, Cornell M, Perrone EE, Manthei DM, Rojas-Peña A, Hirschl RB, Bartlett RH, Mychaliska GB. The role of fetal hemoglobin in the artificial placenta: A premature ovine model. Perfusion 2025; 40:460-465. [PMID: 38519444 PMCID: PMC11416565 DOI: 10.1177/02676591241240725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2024]
Abstract
INTRODUCTION A radical paradigm shift in the treatment of premature infants failing conventional treatment is to recreate fetal physiology using an extracorporeal Artificial Placenta (AP). The aim of this study is to evaluate the effects of changing fetal hemoglobin percent (HbF%) on physiology and circuit function during AP support in an ovine model. METHODS Extremely premature lambs (n = 5) were delivered by cesarean section at 117-121 d estimated gestational age (EGA) (term = 145d), weighing 2.5 ± 0.35 kg. Lambs were cannulated using 10-14Fr cannulae for drainage via the right jugular vein and reinfusion via the umbilical vein. Lambs were intubated and lungs were filled with perfluorodecalin to a meniscus with a pressure of 5-8 cm H2O. The first option for transfusion was fetal whole blood from twins followed by maternal red blood cells. Arterial blood gases were used to titrate AP support to maintain fetal blood gas values. RESULTS The mean survival time on circuit was 119.6 ± 39.5 h. Hemodynamic parameters and lactate were stable throughout. As more adult blood transfusions were given to maintain hemoglobin at 10 mg/dL, the HbF% declined, reaching 40% by post operative day 7. The HbF% was inversely proportional to flow rates as higher flows were required to maintain adequate oxygen saturation and perfusion. CONCLUSIONS Transfusion of adult blood led to decreased fetal hemoglobin concentration during AP support. The HbF% was inversely proportional to flow rates. Future directions include strategies to decrease the priming volume and establishing a fetal blood bank to have blood rich in HbF.
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Affiliation(s)
- Brianna L Spencer
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Brian P Fallon
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jennifer S McLeod
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Marie Cornell
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Erin E Perrone
- Department of Surgery, Section of Pediatric Surgery, University of Michigan Michigan Medicine, Ann Arbor, MI, USA
| | - David M Manthei
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Alvaro Rojas-Peña
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Surgery, Section of Transplantation, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Ronald B Hirschl
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Surgery, Section of Pediatric Surgery, University of Michigan Michigan Medicine, Ann Arbor, MI, USA
| | - Robert H Bartlett
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
| | - George B Mychaliska
- Department of Surgery, ECLS Laboratory, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Surgery, Section of Pediatric Surgery, University of Michigan Michigan Medicine, Ann Arbor, MI, USA
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Hagai A, Anna E, Samantha T, Simcha Y, Alec W. Comparing achievability and reproducibility of pulsed wave Doppler and tissue Doppler myocardial performance index and spatiotemporal image correlation annular plane systolic excursion in the cardiac function assessment of normal pregnancies. J Perinat Med 2025; 53:196-204. [PMID: 39801439 DOI: 10.1515/jpm-2023-0446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 11/11/2024] [Indexed: 03/14/2025]
Abstract
OBJECTIVES Multiple techniques have been proposed for functional fetal cardiology, including pulsed-wave (PW) and tissue Doppler imaging (TDI), Myocardial Performance Index (MPI), annular plane systolic excursion (TAPSE/MAPSE) and spatiotemporal image correlation (STIC). We aimed to compare these techniques' achievability and reproducibility to determine their clinical utility for each cardiac side. METHODS Uncomplicated pregnancies from 22 to 39 weeks were recruited and images and volumes stored for offline analysis. PWD-MPI values were calculated using previously demonstrated automation algorithms, and the remaining volumes were evaluated by two experienced operators. RESULTS Seventy-nine women were scanned generating 222 volumes, with high achievability (>86 %) for all three modalities on both cardiac sides; highest for TAPSE/MAPSE (94 %). Repeatability (ICC) on the right side of the heart was highest for TAPSE (inter-observer 0.86; intraobserver 0.73), compared to PWD-MPI (0.69) and TDI-MPI (0.83). For the left side, repeatability was high for both PWD-MPI (0.80) and TDI-MPI (0.86) though low for MAPSE (inter-observer 0.7, intra-observer 0.69). There was poor correlation between PWD-MPI and TDI-MPI values. CONCLUSIONS TAPSE appears most reliable for evaluation of right heart function, compared to PWD-MPI for the left. As TDI-MPI correlates poorly with PWD-MPI, the latter appears to be the functional tool of choice.
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Affiliation(s)
- Avnet Hagai
- Institute of Obstetrics and Gynecological Imaging and Fetal therapy Sheba Medical center and the Sackler School of Medicine, Tel Aviv University, Tel HaShomer, Israel
| | - Erenbourg Anna
- Perinatal Imaging Research Group, School of Clinical Medicine, Discipline of Women's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Thomas Samantha
- Perinatal Imaging Research Group, School of Clinical Medicine, Discipline of Women's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Yagel Simcha
- Division of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Welsh Alec
- Perinatal Imaging Research Group, School of Clinical Medicine, Discipline of Women's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Maternal- Fetal Medicine, Royal Hospital for Women, Sydney, NSW, Australia
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Phillips M, Nimmo M, Rugonyi S. Developmental and Evolutionary Heart Adaptations Through Structure-Function Relationships. J Cardiovasc Dev Dis 2025; 12:83. [PMID: 40137081 PMCID: PMC11942974 DOI: 10.3390/jcdd12030083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 02/18/2025] [Accepted: 02/20/2025] [Indexed: 03/27/2025] Open
Abstract
While the heart works as an efficient pump, it also has a high level of adaptivity by changing its structure to maintain function during healthy and diseased states. In this Review, we present examples of structure-function relationships across species and throughout embryonic development in mammals and birds. We also summarize current research on avian models aiming at understanding how biophysical and biological mechanisms closely interact during heart formation. We conclude by underscoring similarities between cardiac adaptations and structural changes over developmental and evolutionary time scales and how understanding the mechanisms behind these adaptations can help prevent or alleviate the effects of cardiac malformations and contribute to cardiac regeneration efforts.
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Affiliation(s)
| | | | - Sandra Rugonyi
- Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97239, USA; (M.P.); (M.N.)
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Kozadinos A, Mylonakis A, Bekos F, Kydonakis N, Korovesis G, Kastanaki P, Despotidis M, Chrysikos D, Troupis T. The Development of the Umbilical Vein and Its Anatomical and Clinical Significance. Cureus 2025; 17:e79712. [PMID: 40161047 PMCID: PMC11954436 DOI: 10.7759/cureus.79712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2025] [Indexed: 04/02/2025] Open
Abstract
The umbilical vein is one of the most essential vessels in the human embryo. Anatomical structures though may vary in several cases. During the fourth and eighth weeks of gestation, the umbilical cord is formed. Initially, two umbilical arteries and veins exist. During development, the obliteration of the right umbilical vein occurs. The fetus and its liver receive macronutrients and oxygen from the placenta via the umbilical vein, which primarily supplies the left lobe of the liver before branching into the left portal vein and the ductus venosus. The ductus venosus directs blood from the umbilical vein directly into the systemic circulation through the inferior vena cava and right atrium, bypassing the fetal liver. In some cases, variations are observed. Disorders of the umbilical veins may involve the persistence of embryological structures, abnormal insertion or course, and the presence of supernumerary vessels. For example, the persistence of the right umbilical vein, duplication of the umbilical vein, and umbilical vein varix are some important variations to acknowledge in order to be able to understand the potential outcomes of the newborn. The majority of venous system anomalies are rare, and some may remain completely asymptomatic. Different forms of umbilical cord abnormalities, however, may be potentially fatal or pose a serious threat to fetal health. Therefore, clinically, early detection of these malformations is highly important in order to make a proper diagnosis and management of care. The aim of this study is to acknowledge the different types of umbilical vein variations through its development and its relation with liver parenchyma in order to achieve a better understanding and planning in surgical interventions. An advanced review search of the literature was undertaken. The literature review was conducted using the search engine of the PubMed database and Google Scholar. The years included in data collection were 1960-2022. All articles that met the inclusion criteria were taken under consideration.
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Affiliation(s)
- Alexandros Kozadinos
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Adam Mylonakis
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Filippos Bekos
- Department of Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, GRC
| | - Nikolaos Kydonakis
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Georgios Korovesis
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Pagona Kastanaki
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Markos Despotidis
- First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Dimosthenis Chrysikos
- Department of Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, GRC
| | - Theodore Troupis
- Department of Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, GRC
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Munneke AG, Lumens J, Delhaas T. Diagnostic value of reversed differential cyanosis in (supra)cardiac total anomalous pulmonary venous return. Pediatr Res 2025; 97:809-817. [PMID: 38971943 DOI: 10.1038/s41390-024-03355-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 05/13/2024] [Accepted: 06/07/2024] [Indexed: 07/08/2024]
Abstract
BACKGROUND To investigate the occurrence of reversed differential cyanosis (RDC) in case of (supra)cardiac total anomalous pulmonary venous return (TAPVR), we explored the hemodynamic changes and oxygen saturation levels during the fetal-to-neonatal transition in (supra)cardiac TAPVR, thereby revealing determinant factors of RDC. METHODS A computational model was used to simulate the cardiovascular fetal-to-neonatal transition up to 24 h after birth. Abnormalities associated with TAPVR, like patent ductus arteriosus (PDA) and persistent pulmonary hypertension of the neonate (PPHN), were imposed on the model. Hemodynamic impact on flow distribution and right-sided pressures as well as oxygen saturations were assessed. RESULTS Model findings demonstrated that RDC in (supra)cardiac TAPVR was dependent on two key factors: (1) the type of pulmonary venous connection being supracardiac or cardiac, and (2) the presence of a patent ductus arteriosus exhibiting right-to-left shunting. Persistence of RDC was mainly determined by the latter; an increase in pulmonary-to-systemic pressure difference by PPHN or PDA-induced pulmonary over-circulation contributed to persistence of RDC. CONCLUSION This study highlights the significance of RDC in (supra)cardiac TAPVR and suggests to incorporate early screening ( < 24 h after birth) and to consider RDC as an immediate fail in screening protocols to ensure prompt detection of (supra)cardiac TAPVR. IMPACT Utilizing a validated computational model for the cardiovascular fetal-to-neonatal transition, this study sheds light on the complex hemodynamics in neonates with (supra)cardiac Total Anomalous Pulmonary Venous Return (TAPVR). Model findings suggest that the often-present pulmonary over-circulation in neonates with TAPVR might significantly contribute to the anomaly's frequent omission during pulse-oximetry screening beyond the first 24 h after birth. This study highlights the diagnostic value of reversed differential cyanosis in early screenings within the first 24 h after birth. By including RDC as an immediate fail in early pulse-oximetry screenings, the likelihood of missing (supra)cardiac TAPVR cases could be reduced.
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Affiliation(s)
- Anneloes G Munneke
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - Joost Lumens
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
| | - Tammo Delhaas
- Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
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Başaran E, Öcal FD, Tanaçan A, Ağaoğlu Z, Ipek G, Aktaş BA, Şahin D. Evaluation of fetal aortic isthmus diameter and flow in pregnant women with intrahepatic cholestasis of pregnancy; may it be a marker of poor perinatal outcomes? J Obstet Gynaecol Res 2025; 51:e16222. [PMID: 39887593 DOI: 10.1111/jog.16222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 01/19/2025] [Indexed: 02/01/2025]
Abstract
AIM To evaluate the fetal aortic isthmus (AoI) diameter and flow in pregnant women diagnosed with intrahepatic cholestasis of pregnancy (ICP). METHODS In this prospective case-control study, fetal AoI diameter and Doppler measurements were performed in the ICP group (n: 30) and the control group (n: 42). Clinical characteristics, fetal AoI diameter and Doppler measurements, serum bile acid levels, liver enzyme levels, and obstetric and perinatal outcomes were compared between the groups. RESULTS The AoI diameter was 4.8 ± 0.95 mm in the ICP group and 4.2 ± 0.62 mm in the control group, indicating a statistically significant difference (p = 0.003). The AoI Doppler flow parameters did not significantly differ between the groups (p > 0.05). When evaluated in subgroups according to disease severity, the AoI diameter and Doppler measurements did not significantly differ between the mild and severe ICP cases (p > 0.05). The AoI diameter was significantly larger in those requiring admission to the neonatal intensive care unit (NICU) (p = 0.005). This diameter was also larger in patients with fetal distress, albeit with no statistically significant difference (p = 0.65). CONCLUSIONS ICP is a pathology with known adverse fetal cardiac effects, but there is no effective method to predict adverse perinatal outcomes. The enlarged AoI diameter in the fetuses of mothers with ICP and the association of this enlargement with NICU requirements are important findings of this study. Further research with a larger number of patients is necessary to evaluate the clinical utility of fetal AoI diameter and Doppler parameters in ICP.
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Affiliation(s)
- Ezgi Başaran
- Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
| | - Fatma Doğa Öcal
- Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
| | - Atakan Tanaçan
- University of Health Sciences, Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
| | - Zahid Ağaoğlu
- Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
| | - Göksun Ipek
- Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
| | - Betül Akgün Aktaş
- Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
| | - Dilek Şahin
- University of Health Sciences, Department of Obstetrics and Gynecology, Division of Perinatology, Turkish Ministry of Health Ankara City Hospital, Ankara, Turkey
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Wolfsberger CH, Schwaberger B, Urlesberger B, Avian A, Goeral K, Hammerl M, Perme T, Dempsey EM, Springer L, Lista G, Szczapa T, Fuchs H, Karpinski L, Bua J, Law B, Buchmayer J, Kiechl-Kohlendorfer U, Kornhauser-Cerar L, Schwarz CE, Gründler K, Stucchi I, Klebermass-Schrehof K, Schmölzer GM, Pichler G. Reference Ranges for Arterial Oxygen Saturation, Heart Rate, and Cerebral Oxygen Saturation during Immediate Postnatal Transition in Neonates Born Extremely or Very Preterm. J Pediatr 2024; 273:114132. [PMID: 38823628 DOI: 10.1016/j.jpeds.2024.114132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 04/21/2024] [Accepted: 05/27/2024] [Indexed: 06/03/2024]
Abstract
OBJECTIVE To define percentile charts for arterial oxygen saturation (SpO2), heart rate (HR), and cerebral oxygen saturation (crSO2) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome. STUDY DESIGN We conducted a secondary-outcome analysis of neonates born preterm included in the Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth III (COSGOD III) trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. crSO2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute. RESULTS A total of 207 neonates born preterm with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) g were eligible for analyses. The 10th percentile of SpO2 at minute 2, 5, 10, and 15 was 32%, 52%, 83%, and 85%, respectively. The 10th percentile of HR at minute 2, 5, 10, and 15 was 70, 109, 126, and 134 beats/min, respectively. The 10th percentile of crSO2 at minute 2, 5, 20, and 15 was 15%, 27%, 59%, and 63%, respectively. CONCLUSIONS This study provides new centile charts for SpO2, HR, and crSO2 for neonates born extremely or very preterm with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period.
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Affiliation(s)
- Christina H Wolfsberger
- Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria; Research Unit for Neonatal Micro- and Macrocirculation, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Bernhard Schwaberger
- Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria; Research Unit for Neonatal Micro- and Macrocirculation, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Berndt Urlesberger
- Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria; Research Unit for Neonatal Micro- and Macrocirculation, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | - Alexander Avian
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Katharina Goeral
- Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria
| | - Marlene Hammerl
- Department of Pediatrics II, Neonatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Tina Perme
- NICU, Division of Gynaecology and Obstetrics, Department for Perinatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Eugene M Dempsey
- INFANT Research Centre, University College Cork, Cork University Maternity Hospital, Cork, Ireland
| | - Laila Springer
- Department of Neonatology, University Children's Hospital of Tübingen, Tübingen, Germany
| | - Gianluca Lista
- Neonatologia e Terapia Intensiva Neonatale (TIN) Ospedale dei Bambini "V Buzzi," Milano, Italy
| | - Tomasz Szczapa
- II Department of Neonatology, Neonatal Biophysical Monitoring and Cardiopulmonary Therapies Research Unit, Poznan University of Medical Sciences, Poznan, Poland
| | - Hans Fuchs
- Division of Neonatology and Pediatric Intensive Care Medicine, Center for Pediatrics and Adolescent Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Lukasz Karpinski
- II Department of Neonatology, Neonatal Biophysical Monitoring and Cardiopulmonary Therapies Research Unit, Poznan University of Medical Sciences, Poznan, Poland
| | - Jenny Bua
- Neonatal Intensive Care Unit, Institute for Maternal and Child Health, Trieste, Italy
| | - Brenda Law
- Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Julia Buchmayer
- Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria
| | | | - Lilijana Kornhauser-Cerar
- NICU, Division of Gynaecology and Obstetrics, Department for Perinatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Christoph E Schwarz
- INFANT Research Centre, University College Cork, Cork University Maternity Hospital, Cork, Ireland
| | - Kerstin Gründler
- Department of Neonatology, University Children's Hospital of Tübingen, Tübingen, Germany
| | - Ilaria Stucchi
- Neonatologia e Terapia Intensiva Neonatale (TIN) Ospedale dei Bambini "V Buzzi," Milano, Italy
| | - Katrin Klebermass-Schrehof
- Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria
| | - Georg M Schmölzer
- Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Gerhard Pichler
- Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria; Research Unit for Neonatal Micro- and Macrocirculation, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
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10
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Torcia E, Familiari A, Passananti E, di Marco G, Romanzi F, Trapani M, Visconti D, Lanzone A, Bevilacqua E. Ductus Venosus Agenesis in Monochorionic Twin Pregnancies Complicated by Fetal Growth Restriction: When to Deliver? Diagnostics (Basel) 2024; 14:2147. [PMID: 39410550 PMCID: PMC11475775 DOI: 10.3390/diagnostics14192147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/22/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Introduction: The prevalence of ductus venosus agenesis (ADV) in singleton pregnancies ranges from 0.04% to 0.15%, while its prevalence in twins remains largely unknown. To our knowledge, in the literature, there is only a single case report of a monochorionic diamniotic (MCDA) pregnancy complicated by ADV. Fetuses with ADV are at increased risk for congenital cardiac disease, heart failure, and fetal growth restriction (FGR). Consequently, these pregnancies have a heightened risk of experiencing an adverse outcome, like stillbirth and neonatal or infant death. Closer antenatal monitoring is warranted when ADV is suspected. Currently, there are no guidelines regarding the standard of care in cases of ADV and no recommendations for the timing of delivery in either singleton or twin pregnancies. Cases: This study aims to provide a comprehensive overview of the management of twin pregnancies complicated by ADV, featuring two cases of MC twins with concurrent sFGR and ADV in one twin. Discussion: These pregnancies experienced completely different outcomes, underscoring the necessity for personalized management tailored to the specific risk factors present in each pregnancy. Typically, in MCDA pregnancies with severe sFGR (type II and III), delivery represents the most reasonable option when venous Doppler abnormalities are identified. However, the absence of the DV complicates the management and the process of decision-making regarding the timing of delivery in cases of sFGR and ADV. We emphasize that effective decision-making should be guided by the presence of additional risk factors, including velamentous insertion, significant estimated fetal weight discordance, and progressive deterioration of the Doppler over time. Conclusions: Our experience suggests that these factors are strongly correlated with poorer outcomes. Given this context, could it be acceptable, in the case of MC pregnancy complicated by severe sFGR and ADV, with worsening findings and additional risk factors (e.g., velamentous insertion, severe birth weight discrepancy), to anticipate the time of delivery starting from 30 weeks of gestational age?
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Affiliation(s)
- Eleonora Torcia
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
| | - Alessandra Familiari
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
- Unit of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Elvira Passananti
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
| | - Giulia di Marco
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
| | - Federica Romanzi
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
| | - Mariarita Trapani
- Unit of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Daniela Visconti
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
| | - Antonio Lanzone
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
- Unit of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Elisa Bevilacqua
- Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy; (E.T.); (A.F.); (E.P.); (G.d.M.); (F.R.); (D.V.); (A.L.)
- Unit of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
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11
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Chakkarapani AA, Roehr CC, Hooper SB, Te Pas AB, Gupta S. Transitional circulation and hemodynamic monitoring in newborn infants. Pediatr Res 2024; 96:595-603. [PMID: 36593283 PMCID: PMC11499276 DOI: 10.1038/s41390-022-02427-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 11/14/2022] [Accepted: 11/21/2022] [Indexed: 01/03/2023]
Abstract
Transitional circulation is normally transient after birth but can vary markedly between infants. It is actually in a state of transition between fetal (in utero) and neonatal (postnatal) circulation. In the absence of definitive clinical trials, information from applied physiological studies can be used to facilitate clinical decision making in the presence of hemodynamic compromise. This review summarizes the peculiar physiological features of the circulation as it transitions from one phenotype into another in term and preterm infants. The common causes of hemodynamic compromise during transition, intact umbilical cord resuscitation, and advanced hemodynamic monitoring are discussed. IMPACT: Transitional circulation can vary markedly between infants. There are alterations in preload, contractility, and afterload during the transition of circulation after birth in term and preterm infants. Hemodynamic monitoring tools and technology during neonatal transition and utilization of bedside echocardiography during the neonatal transition are increasingly recognized. Understanding the cardiovascular physiology of transition can help clinicians in making better decisions while managing infants with hemodynamic compromise. The objective assessment of cardio-respiratory transition and understanding of physiology in normal and disease states have the potential of improving short- and long-term health outcomes.
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Affiliation(s)
| | - Charles C Roehr
- National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK
- Newborn Services, Southmead Hospital, North Bristol Trust, Bristol, UK
- Faculty of Health Sciences, University of Bristol, Bristol, UK
| | - Stuart B Hooper
- Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, Australia
- The Ritchie Centre, Hudson Institute for Medical Research, Melbourne, VIC, Australia
| | - Arjan B Te Pas
- Neonatology, Willem Alexander Children's Hospital, Leiden University Medical Center Leiden, Leiden, The Netherlands
| | - Samir Gupta
- Division of Neonatology, Sidra Medicine, Doha, Qatar.
- Durham University, Durham, UK.
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12
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Cromb D, Uus A, Van Poppel MP, Steinweg JK, Bonthrone AF, Maggioni A, Cawley P, Egloff A, Kyriakopolous V, Matthew J, Price A, Pushparajah K, Simpson J, Razavi R, DePrez M, Edwards D, Hajnal J, Rutherford M, Lloyd DF, Counsell SJ. Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease. J Magn Reson Imaging 2024; 60:497-509. [PMID: 37846811 PMCID: PMC7616254 DOI: 10.1002/jmri.29078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/30/2023] [Accepted: 10/02/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear. PURPOSE To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes. STUDY TYPE Retrospective case-control study. POPULATION Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery. FIELD STRENGTH/SEQUENCE T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner. ASSESSMENT Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups. STATISTICAL TESTS ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR-values <0.05 were considered statistically significant. RESULTS Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios. DATA CONCLUSION Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal. EVIDENCE LEVEL 3 TECHNICAL EFFICACY: Stage 3.
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Affiliation(s)
- Daniel Cromb
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Alena Uus
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Milou P.M. Van Poppel
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Department of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Science, King’s College London, London, UK
- Paediatric and Fetal Cardiology Department, Evelina London Children’s Hospital, London, UK
| | - Johannes K. Steinweg
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Department of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Science, King’s College London, London, UK
- Paediatric and Fetal Cardiology Department, Evelina London Children’s Hospital, London, UK
| | - Alexandra F. Bonthrone
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Alessandra Maggioni
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Paul Cawley
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK
| | - Alexia Egloff
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Vanessa Kyriakopolous
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Jacqueline Matthew
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Anthony Price
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Kuberan Pushparajah
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Department of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Science, King’s College London, London, UK
- Paediatric and Fetal Cardiology Department, Evelina London Children’s Hospital, London, UK
| | - John Simpson
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Department of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Science, King’s College London, London, UK
- Paediatric and Fetal Cardiology Department, Evelina London Children’s Hospital, London, UK
| | - Reza Razavi
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Maria DePrez
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - David Edwards
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Jo Hajnal
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
| | - Mary Rutherford
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK
| | - David F.A. Lloyd
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
- Department of Cardiovascular Imaging, School of Biomedical Engineering and Imaging Science, King’s College London, London, UK
- Paediatric and Fetal Cardiology Department, Evelina London Children’s Hospital, London, UK
| | - Serena J. Counsell
- Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
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13
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Chioma R, Finn D, Healy DB, Herlihy I, Livingstone V, Panaviene J, Dempsey EM. Impact of cord clamping on haemodynamic transition in term newborn infants. Arch Dis Child Fetal Neonatal Ed 2024; 109:287-293. [PMID: 38071517 DOI: 10.1136/archdischild-2023-325652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 10/27/2023] [Indexed: 04/20/2024]
Abstract
OBJECTIVE To assess the haemodynamic consequences of cord clamping (CC) in healthy term infants. DESIGN Cohort study. SETTING Tertiary maternity hospital. PATIENTS 46 full-term vigorous infants born by caesarean section. INTERVENTIONS Echocardiography was performed before CC, immediately after CC and at 5 min after birth. MAIN OUTCOME MEASURES Pulsed wave Doppler-derived cardiac output and the pulmonary artery acceleration time indexed to the right ventricle ejection time were obtained. As markers of loading fluctuations, the myocardial performance indexes and the velocities of the tricuspid and mitral valve annuli were determined with tissue Doppler imaging. Heart rate was derived from Doppler imaging throughout the assessments. RESULTS Left ventricular output increased throughout the first minutes after birth (mean (SD) 222.4 (32.5) mL/kg/min before CC vs 239.7 (33.6) mL/kg/min at 5 min, p=0.01), while right ventricular output decreased (306.5 (48.2) mL/kg/min before vs 272.8 (55.5) mL/kg/min immediately after CC, p=0.001). The loading conditions of both ventricles were transiently impaired by CC, recovering at 5 min. Heart rate progressively decreased after birth, following a linear trend temporarily increased by CC. The variation in left ventricular output across the CC was directly correlated to the fluctuation of left ventricular preload over the same period (p=0.03). CONCLUSIONS This study illustrates the cardiovascular consequences of CC in term vigorous infants and offers insight into the haemodynamic transition from fetal to neonatal circulation in spontaneously breathing newborns. Strategies that aim to enhance left ventricular preload before CC may prevent complications of perinatal cardiovascular imbalance.
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Affiliation(s)
- Roberto Chioma
- University College Cork, INFANT Research Centre, Cork, Ireland
- Università Cattolica del Sacro Cuore, Roma, Italy
| | - Daragh Finn
- University College Cork, INFANT Research Centre, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - David B Healy
- University College Cork, INFANT Research Centre, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Ita Herlihy
- University College Cork, INFANT Research Centre, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Vicki Livingstone
- University College Cork, INFANT Research Centre, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Jurate Panaviene
- University College Cork, INFANT Research Centre, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Eugene M Dempsey
- University College Cork, INFANT Research Centre, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
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14
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Ahmed MS, Nguyen NUN, Nakada Y, Hsu CC, Farag A, Lam NT, Wang P, Thet S, Menendez-Montes I, Elhelaly WM, Lou X, Secco I, Tomczyk M, Zentilin L, Pei J, Cui M, Dos Santos M, Liu X, Liu Y, Zaha D, Walcott G, Tomchick DR, Xing C, Zhang CC, Grishin NV, Giacca M, Zhang J, Sadek HA. Identification of FDA-approved drugs that induce heart regeneration in mammals. NATURE CARDIOVASCULAR RESEARCH 2024; 3:372-388. [PMID: 39183959 PMCID: PMC11343477 DOI: 10.1038/s44161-024-00450-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/06/2024] [Indexed: 08/27/2024]
Abstract
Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro-Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals.
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Affiliation(s)
- Mahmoud Salama Ahmed
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- These authors contributed equally: Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen
| | - Ngoc Uyen Nhi Nguyen
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- These authors contributed equally: Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen
| | - Yuji Nakada
- Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ching-Cheng Hsu
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ayman Farag
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Nicholas T. Lam
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ping Wang
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Suwannee Thet
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ivan Menendez-Montes
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Waleed M. Elhelaly
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Xi Lou
- Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ilaria Secco
- School of Cardiovascular and Metabolic Medicine & Sciences and British Heart Foundation Centre of Research Excellence, King’s College London, London, UK
| | - Mateusz Tomczyk
- School of Cardiovascular and Metabolic Medicine & Sciences and British Heart Foundation Centre of Research Excellence, King’s College London, London, UK
| | - Lorena Zentilin
- Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
| | - Jimin Pei
- Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Miao Cui
- Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Matthieu Dos Santos
- Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Xiaoye Liu
- Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Yan Liu
- Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - David Zaha
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Gregory Walcott
- Division of Cardiovascular Diseases, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Diana R. Tomchick
- Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Chao Xing
- Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Cheng Cheng Zhang
- Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Nick V. Grishin
- Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Mauro Giacca
- School of Cardiovascular and Metabolic Medicine & Sciences and British Heart Foundation Centre of Research Excellence, King’s College London, London, UK
- Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Jianyi Zhang
- Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Hesham A. Sadek
- Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
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15
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Perez-Ramirez CA, Nakano H, Law RC, Matulionis N, Thompson J, Pfeiffer A, Park JO, Nakano A, Christofk HR. Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy. Cell 2024; 187:204-215.e14. [PMID: 38070508 PMCID: PMC10843853 DOI: 10.1016/j.cell.2023.11.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/27/2023] [Accepted: 11/08/2023] [Indexed: 01/07/2024]
Abstract
Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.
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Affiliation(s)
- Cesar A Perez-Ramirez
- Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA
| | - Haruko Nakano
- Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA
| | - Richard C Law
- Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, CA 90095, USA
| | - Nedas Matulionis
- Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA
| | - Jennifer Thompson
- Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA
| | - Andrew Pfeiffer
- Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA
| | - Junyoung O Park
- Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA
| | - Atsushi Nakano
- Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
| | - Heather R Christofk
- Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
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16
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Massarwa A, Weissbach T, Hadi E, YuLzari V, Messing B, Adamo L, Elkan-Miller T, Achiron R, Kivilevich Z, Bart Y, Weisz B, Yoeli-Ullman R, Mazaki S, Kassif E. In-utero evaluation of the fetal umbilical-portal venous system among fetuses with persistent right umbilical vein: Two-and three-dimensional ultrasonographic study. Prenat Diagn 2024; 44:68-76. [PMID: 38172082 DOI: 10.1002/pd.6494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 11/02/2023] [Accepted: 12/02/2023] [Indexed: 01/05/2024]
Abstract
OBJECTIVE The aim of this study was to describe the anatomy of the portal system in fetuses with persistent right umbilical vein (PRUV). METHODS Prospective observational study of fetuses diagnosed with PRUV. All patients underwent a comprehensive portal system anatomy scan supplemented by two-dimensional (2D) and three-dimensional (3D) color doppler modalities. RESULTS 29 fetuses with PRUV were studied. We perceived an identical anatomical pattern in 28 fetuses. The right umbilical vein drains to the portal sinus (future right portal vein, RPV), which has a configuration of a left portal vein (LPV) in the normal left portal system, with three emerging branches: inferior (RPVi), medial (RPVm) and superior (RPVs). The RPV then courses to the left, towards the stomach to the point of the bifurcation of the main portal vein (MPV) to become the left portal vein. The LPV has an RPV configuration in a normal portal system with anterior (LPVa) and posterior (RPVp) branches. This anatomical layout mimics a mirror image of the normal anatomy of left portal system. CONCLUSION PRUV has unique umbilical portal venous anatomy, which is a mirror image of the normal left portal system. It can be demonstrated prenatally and serve as an additional tool for prenatal diagnosis of PRUV.
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Affiliation(s)
- Abeer Massarwa
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tal Weissbach
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Efrat Hadi
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Vered YuLzari
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Baruch Messing
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Laura Adamo
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
| | - Tal Elkan-Miller
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Reuven Achiron
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Zvi Kivilevich
- Maccabi Health Services, Ultrasound Unit, The Negev Medical Center, Beer Sheba, Israel
| | - Yossi Bart
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Boaz Weisz
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Rakefet Yoeli-Ullman
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shali Mazaki
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eran Kassif
- Department of Obstetrics and Gynecology, Diagnostic Ultrasound Unit, Sheba Medical Center, Institute of Obstetrical and Gynecological Imaging, Tel-Hashomer, Ramat Gan, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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17
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Ali SK, Stanford AH, McNamara PJ, Gupta S. Surfactant and neonatal hemodynamics during the postnatal transition. Semin Fetal Neonatal Med 2023; 28:101498. [PMID: 38040585 DOI: 10.1016/j.siny.2023.101498] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2023]
Abstract
Surfactant replacement therapy (SRT) has revolutionized the management of respiratory distress syndrome (RDS) in premature infants, leading to improved survival rates and decreased morbidity. SRT may, however, be associated with hemodynamic changes, which can have both positive and negative effects on the immature cardiovascular system, during the transitional adaptation from fetal to extrauterine environment. However, there is a relative paucity of evidence in this domain, with most of them derived from small heterogeneous observational studies providing conflicting results. In this review, we will discuss the hemodynamic changes that occur with surfactant administration during this vulnerable period, focusing on available evidence regarding changes in pulmonary and systemic blood flow, cerebral circulation and their clinical implications.
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Affiliation(s)
- Sanoj Km Ali
- Division of Neonatology, Sidra Medicine, Doha, Qatar; University of Tasmania, Australia; Murdoch Children's Research Institute, Melbourne, Australia.
| | - Amy H Stanford
- Pediatrics - Neonatology, Department of Pediatrics, University of Iowa, Iowa City, LW, USA.
| | - Patrick J McNamara
- Division of Neonatology, Department of Pediatrics and Internal Medicine, University of Iowa, Iowa City, LW, USA.
| | - Samir Gupta
- Department of Engineering, Durham University, United Kingdom; Division of Neonatology, Department of Pediatrics, Sidra Medicine, Doha, Qatar.
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18
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Ma Y, Sun X, Liu X, Hu L, Song Y, Ye X. Fetal echocardiography changes of the right ventricle of well-controlled gestational diabetes mellitus. BMC Cardiovasc Disord 2023; 23:493. [PMID: 37803261 PMCID: PMC10559588 DOI: 10.1186/s12872-023-03539-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 09/27/2023] [Indexed: 10/08/2023] Open
Abstract
BACKGROUND There is few evidence of right ventricular (RV) function in fetuses with gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the RV function of fetuses using routine and two-dimensional speckle-tracking echocardiography (2D STE) to determine the effects of well-controlled GDM in the third trimester. METHODS We used a Philips Epiq7C ultrasound instrument to obtain RV data sets from 63 subjects from July 2019 to February 2022. We compared the free wall thickness (FWT), fractional area change (FAC), Tei index (TEI), tricuspid annular plane systolic excursion (TAPSE) and free wall longitudinal strain(FWLS)of the RV in mothers with well-controlled GDM and normal gestational age-matched fetuses. RESULTS 63 third trimester fetuses (32 GDM; 31 healthy controls) met the enrolment criteria. Significant differences in fetal RV were detected between the GDM and control groups for the FAC (36.35 ± 6.19 vs. 41.59 ± 9.11; P = 0.008) and the FWLS (-18.28 ± 4.23 vs. -20.98 ± 5.49; P = 0.021). There was a significant difference among the segmental strains of the base, middle and apex of the RV free wall in the healthy controls (P = 0.003), but in the GDM group, there was no statistical difference (p = 0.076). RV FWLS had a strong correlation with FAC (r = 0.467; P = 0.0002). CONCLUSIONS In well-controlled GDM, there was measurable fetal RV hypertrophy and significant systolic function decline, indicating the presence of ventricular remodeling and dysfunction. 2D-STE can evaluate the RV free wall contraction in a more comprehensive way.
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Affiliation(s)
- Ying Ma
- Department of Ultrasound, Zhou Pu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - XueSong Sun
- Department of Obstetrics and Gynecology, Zhou Pu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - XiaoZhi Liu
- Department of Obstetrics and Gynecology, Zhou Pu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - LiHua Hu
- Department of Ultrasound, Zhou Pu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Ye Song
- Department of Ultrasound, Zhou Pu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Xiong Ye
- School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China.
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19
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Portela Dias J, Guedes-Martins L. Fetal Pulmonary Venous Return: From Basic Research to the Clinical Value of Doppler Assessment. Pediatr Cardiol 2023; 44:1419-1437. [PMID: 37505268 PMCID: PMC10435640 DOI: 10.1007/s00246-023-03244-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 07/20/2023] [Indexed: 07/29/2023]
Abstract
The fetal pulmonary circulation represents less than 25% of the fetal cardiac output. In comparison with the pulmonary arteries, studies on pulmonary veins are few and limited, and many questions remain to be answered. The literature reports that pulmonary veins play an important role in regulating vascular flow, forming an active segment of the pulmonary circulation. The development of more sophisticated ultrasonography technology has allowed the investigation of the extraparenchymal pulmonary veins and their waveform. The recognition of the pulmonary vein anatomy in echocardiography is important for the diagnosis of anomalous pulmonary venous connections, with a significant impact on prognosis. On the other hand, the identification of the normal pulmonary vein waveform seems to be a reliable way to study left heart function, with potential applicability in fetal and maternal pathology. Thus, the goal of this narrative review was to provide a clinically oriented perspective of the available literature on this topic.
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Affiliation(s)
- J Portela Dias
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313, Porto, Portugal.
- Departamento da Mulher e da Medicina Reprodutiva, Centro Materno Infantil do Norte, Centro Hospitalar e Universitário de Santo António, Largo da Maternidade Júlio Dinis 45, 4050-651, Porto, Portugal.
- Unidade de Investigação e Formação - Centro Materno Infantil do Norte, 4050-651, Porto, Portugal.
| | - L Guedes-Martins
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313, Porto, Portugal
- Departamento da Mulher e da Medicina Reprodutiva, Centro Materno Infantil do Norte, Centro Hospitalar e Universitário de Santo António, Largo da Maternidade Júlio Dinis 45, 4050-651, Porto, Portugal
- Unidade de Investigação e Formação - Centro Materno Infantil do Norte, 4050-651, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Porto, Portugal
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20
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Słodki M, Sylwestrzak O. Prenatal ultrasound assessment of fetal lung development in normal and complicated by fetal and maternal diseases pregnancy. JOURNAL OF CLINICAL ULTRASOUND : JCU 2023; 51:992-994. [PMID: 37218338 DOI: 10.1002/jcu.23491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 05/09/2023] [Indexed: 05/24/2023]
Affiliation(s)
- Maciej Słodki
- Medicine Faculty, Mazovian Academy in Plock, Plock, Poland
- Department of Prenatal Cardiology, Polish Mother's Memorial Hospital Research Institute in Lodz, Lodz, Poland
| | - Oskar Sylwestrzak
- Medicine Faculty, Mazovian Academy in Plock, Plock, Poland
- Department of Obstetrics and Gynecology, Polish Mother's Memorial Hospital Research Institute in Lodz, Lodz, Poland
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21
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Zhang D, Lindsey SE. Recasting Current Knowledge of Human Fetal Circulation: The Importance of Computational Models. J Cardiovasc Dev Dis 2023; 10:240. [PMID: 37367405 PMCID: PMC10299027 DOI: 10.3390/jcdd10060240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/16/2023] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Computational hemodynamic simulations are becoming increasingly important for cardiovascular research and clinical practice, yet incorporating numerical simulations of human fetal circulation is relatively underutilized and underdeveloped. The fetus possesses unique vascular shunts to appropriately distribute oxygen and nutrients acquired from the placenta, adding complexity and adaptability to blood flow patterns within the fetal vascular network. Perturbations to fetal circulation compromise fetal growth and trigger the abnormal cardiovascular remodeling that underlies congenital heart defects. Computational modeling can be used to elucidate complex blood flow patterns in the fetal circulatory system for normal versus abnormal development. We present an overview of fetal cardiovascular physiology and its evolution from being investigated with invasive experiments and primitive imaging techniques to advanced imaging (4D MRI and ultrasound) and computational modeling. We introduce the theoretical backgrounds of both lumped-parameter networks and three-dimensional computational fluid dynamic simulations of the cardiovascular system. We subsequently summarize existing modeling studies of human fetal circulation along with their limitations and challenges. Finally, we highlight opportunities for improved fetal circulation models.
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Affiliation(s)
| | - Stephanie E. Lindsey
- Department of Mechanical and Aerospace Engineering, University of California, San Diego, CA 92093, USA;
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22
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Koo J, Kilicdag H, Katheria A. Umbilical cord milking-benefits and risks. Front Pediatr 2023; 11:1146057. [PMID: 37144151 PMCID: PMC10151786 DOI: 10.3389/fped.2023.1146057] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 04/03/2023] [Indexed: 05/06/2023] Open
Abstract
The most common methods for providing additional placental blood to a newborn are delayed cord clamping (DCC) and umbilical cord milking (UCM). However, DCC carries the potential risk of hypothermia due to extended exposure to the cold environment in the operating room or delivery room, as well as a delay in performing resuscitation. As an alternative, umbilical cord milking (UCM) and delayed cord clamping with resuscitation (DCC-R) have been studied, as they allow for immediate resuscitation after birth. Given the relative ease of performing UCM compared to DCC-R, UCM is being strongly considered as a practical option in non-vigorous term and near-term neonates, as well as preterm neonates requiring immediate respiratory support. However, the safety profile of UCM, particularly in premature newborns, remains a concern. This review will highlight the currently known benefits and risks of umbilical cord milking and explore ongoing studies.
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Affiliation(s)
- Jenny Koo
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, United States
| | - Hasan Kilicdag
- Divisions of Neonatology, Baskent University Faculty of Medicine, Ankara, Türkiye
| | - Anup Katheria
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, United States
- Correspondence: Anup Katheria
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23
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Rocha LIQ, Oliveira MFDS, Dias LC, Franco de Oliveira M, de Moura CEB, Magalhães MDS. Heart morphology during the embryonic development of Podocnemis unifilis Trosquel 1948 (Testudines: Podocnemididae). Anat Rec (Hoboken) 2023; 306:193-212. [PMID: 35808951 DOI: 10.1002/ar.25041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/09/2022] [Accepted: 06/27/2022] [Indexed: 01/29/2023]
Abstract
Cardiogenesis is similar in all vertebrates, but differences in the valvuloseptal morphogenesis among non-crocodilian reptiles, birds, and mammals are noted. The origin of mesenchymal structures such as valves that regulate the passage of blood and the formation of partial septa that prevent the complete mixing of oxygen-rich and low-oxygen blood present in adult chelonians are essential in the evolutionary understanding of complete septation, endothermy and malformations, even in mammals. In this context, this study analyzed the heart morphogenesis of Podocnemis unifilis (Testudines: Podocnemididae) from the 4th to the 60th day of incubation. We identified the tubular heart stage, folding of the cardiac tube and expansion of the atrial and ventricular compartments followed by atrial septation by the septum primum, ventricle septation by partial septa, outflow tract septation and the formation of bicuspid valves with cartilage differentiation at the base. The formation of the first atrial septum with the mesenchymal cap is noted during the development of the atrial septum, joining the atrioventricular cushion on the 17th day and completely dividing the atria. Small secondary perforations appeared in the mid-cranial part, observed up to the 45th day. Partial ventricle septation into the pulmonary, venous, and arterial subcompartments takes place by trabeculae carneae thickening and grouping on the 15th day. The outflow tract forms the aorticopulmonary and interaortic septa on the 16th day and the bicuspid valves, on the 20th day. Therefore, after the first 20 days, the heart exhibits a general anatomical conformation similar to that of adult turtles.
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Affiliation(s)
- Layla Ianca Queiroz Rocha
- Programa de Pós-graduação em Biologia de Água Doce e Pesca Interior, Instituto Nacional de Pesquisas da Amazônia, Manaus, Amazonas, Brazil
| | - Maria Fabiele da Silva Oliveira
- Programa de Pós-graduação em Biologia de Água Doce e Pesca Interior, Instituto Nacional de Pesquisas da Amazônia, Manaus, Amazonas, Brazil
| | - Lucas Castanhola Dias
- Laboratório Temático de Microscopia e Nanotecnologia, Instituto Nacional de Pesquisas da Amazônia, Manaus, Amazonas, Brazil
| | - Moacir Franco de Oliveira
- Departamento de Ciências Animais, Universidade Federal Rural do Semi-Árido, Mossoró, Rio Grande do Norte, Brazil
| | | | - Marcela Dos Santos Magalhães
- Programa de Pós-graduação em Biologia de Água Doce e Pesca Interior, Instituto Nacional de Pesquisas da Amazônia, Manaus, Amazonas, Brazil.,Departamento de Morfologia, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil
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24
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Kapraun DF, Sfeir M, Pearce RG, Davidson-Fritz SE, Lumen A, Dallmann A, Judson RS, Wambaugh JF. Evaluation of a rapid, generic human gestational dose model. Reprod Toxicol 2022; 113:172-188. [PMID: 36122840 PMCID: PMC9761697 DOI: 10.1016/j.reprotox.2022.09.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 08/30/2022] [Accepted: 09/14/2022] [Indexed: 10/14/2022]
Abstract
Chemical risk assessment considers potentially susceptible populations including pregnant women and developing fetuses. Humans encounter thousands of chemicals in their environments, few of which have been fully characterized. Toxicokinetic (TK) information is needed to relate chemical exposure to potentially bioactive tissue concentrations. Observational data describing human gestational exposures are unavailable for most chemicals, but physiologically based TK (PBTK) models estimate such exposures. Development of chemical-specific PBTK models requires considerable time and resources. As an alternative, generic PBTK approaches describe a standardized physiology and characterize chemicals with a set of standard physical and TK descriptors - primarily plasma protein binding and hepatic clearance. Here we report and evaluate a generic PBTK model of a human mother and developing fetus. We used a published set of formulas describing the major anatomical and physiological changes that occur during pregnancy to augment the High-Throughput Toxicokinetics (httk) software package. We simulated the ratio of concentrations in maternal and fetal plasma and compared to literature in vivo measurements. We evaluated the model with literature in vivo time-course measurements of maternal plasma concentrations in pregnant and non-pregnant women. Finally, we prioritized chemicals measured in maternal serum based on predicted fetal brain concentrations. This new model can be used for TK simulations of 859 chemicals with existing human-specific in vitro TK data as well as any new chemicals for which such data become available. This gestational model may allow for in vitro to in vivo extrapolation of point of departure doses relevant to reproductive and developmental toxicity.
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Affiliation(s)
- Dustin F Kapraun
- Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
| | - Mark Sfeir
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA; Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA
| | - Robert G Pearce
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA; Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA
| | - Sarah E Davidson-Fritz
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
| | - Annie Lumen
- National Center for Toxicological Research, US Food and Drug Administration, USA
| | - André Dallmann
- Pharmacometrics/Modeling and Simulation, Research and Development, Pharmaceuticals, Bayer AG, Leverkusen, Germany
| | - Richard S Judson
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
| | - John F Wambaugh
- Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
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25
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Desoye G, Carter AM. Fetoplacental oxygen homeostasis in pregnancies with maternal diabetes mellitus and obesity. Nat Rev Endocrinol 2022; 18:593-607. [PMID: 35902735 DOI: 10.1038/s41574-022-00717-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2022] [Indexed: 11/09/2022]
Abstract
Despite improvements in clinical management, pregnancies complicated by pre-existing diabetes mellitus, gestational diabetes mellitus or obesity carry substantial risks for parent and offspring. Some of the endocrine and metabolic changes in parent and fetus in diabetes mellitus and obesity lead to fetal oxygen deficit, mostly due to insulin-induced accelerated fetal metabolism. The human fetus deals with reduced oxygenation through a wide range of adaptive responses that act at various levels in the placenta as well as the fetus. These responses ensure adequate oxygen delivery to the fetus, increase the oxygen transport capacity of fetal blood and redistribute oxygen-rich blood to vital organs such as the brain and heart. The liver has a central role in adapting to reduced oxygenation by increasing its oxygen extraction and stimulating erythropoietin synthesis to increase haematocrit. The type of adaptive response depends on the onset and duration of hypoxia and the severity of the metabolic disturbance. In pregnancies characterized by diabetes mellitus or obesity, these adaptive systems come under additional strain owing to the increased maternal supply of glucose and resultant fetal hyperinsulinaemia, both of which stimulate oxidative metabolism. In the rare situation that the adaptive responses are overwhelmed, stillbirth can ensue.
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Affiliation(s)
- Gernot Desoye
- Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria.
- Center for Pregnant Women with Diabetes, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
| | - Anthony M Carter
- Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
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26
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Mahmood B. Persistent pulmonary hypertension of newborn. Semin Pediatr Surg 2022; 31:151202. [PMID: 36038220 DOI: 10.1016/j.sempedsurg.2022.151202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Burhan Mahmood
- Division of Newborn Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pennsylvania, USA.
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27
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Graupner O, Kuschel B, Axt-Fliedner R, Enzensberger C. New Markers for Placental Dysfunction at Term - Potential for More. Geburtshilfe Frauenheilkd 2022; 82:719-726. [PMID: 35815096 PMCID: PMC9262629 DOI: 10.1055/a-1761-1337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 02/03/2022] [Indexed: 11/23/2022] Open
Abstract
The remaining placental reserve capacity at term plays a decisive role in the perinatal morbidity of mother and child. Considering advances made in the field of fetal monitoring, the
routine examination methods currently used at term or late term may be insufficient to detect subclinical placental dysfunction (PD). The aim of this study is to offer an up-to-date,
narrative review of the literature in the context of detecting PD at term using complementary ultrasound markers and biomarkers. Parameters of fetomaternal Doppler ultrasound and fetal
cardiac function, as well as (anti-)angiogenic factors in maternal serum are potential PD markers. These may help identify patients that may benefit from an elective, early induction of
labor at term, thereby potentially reducing morbidity and mortality. However, their value in terms of the optimal date of delivery must first be determined in randomized controlled trials on
a large number of cases.
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Affiliation(s)
- Oliver Graupner
- Klinik für Gynäkologie und Geburtsmedizin, Universitätsklinikum Aachen, RWTH Aachen, Aachen.,Frauenklinik und Poliklinik, Universitätsklinikum rechts der Isar, Technische Universität München, München
| | - Bettina Kuschel
- Frauenklinik und Poliklinik, Universitätsklinikum rechts der Isar, Technische Universität München, München
| | - Roland Axt-Fliedner
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum UKGM, Justus-Liebig-Universität Gießen, Gießen
| | - Christian Enzensberger
- Klinik für Gynäkologie und Geburtsmedizin, Universitätsklinikum Aachen, RWTH Aachen, Aachen
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28
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Vasquez-Hidalgo MA, Swanson KC, Vonnahme KA. Effects of Mid-Gestation Nutrient Restriction, Realimentation, and Parity on the Umbilical Hemodynamics of the Pregnant Ewe. FRONTIERS IN ANIMAL SCIENCE 2022. [DOI: 10.3389/fanim.2022.855345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Previous studies have reported that nutritional restriction from days 50 to 130 applied in young nulliparous ewes reduces umbilical blood flow (UBF). We hypothesized that during restriction, UBF and fetal and placentome dimensional measurements would decrease compared to adequately fed ewes, but upon realimentation, ewes would have similar UBF as ewes that were not restricted. We also hypothesized that multiparous ewes would be more resilient to nutrient restriction compared to nulliparous ewes. In experiment 1, second-parity Dorset ewes carrying singletons were assigned to an adequate nutrition group (CON, n = 7) or a restricted (60% of CON) group (RES, n = 8), from days 50 to 90 of gestation. In experiment 2, on day 50 of gestation, adult (15-month) nulliparous (NUL; n = 12) and multiparous (MUL; n = 16) Dorset ewes carrying singletons were randomly assigned to receive 100% of NRC recommendations (CON) or 60% of CON (RES). On day 90, all ewes were fed 100% of nutritional recommendations according to body weight. Ewe body weight and conceptus measurements via ultrasonography were recorded every 10 days from days 50 to 130 of gestation. We measured 10 random placentomes, fetal biparietal and abdominal length, and kidney length and width. Doppler mode was used to obtain UBF, pulsatility index (PI), and resistance index (RI). Lamb weight and parturition problems were recorded. In experiment 1, on day 80, UBF decreased (P ≤ 0.05 means separation of unprotected F test), placentome size tended to decrease (P ≤ 0.10), and PI and RI tended to increase in RES vs. CON ewes (P ≤ 0.10). In experiment 2, there were no three-way interactions or main effects of treatments on UBF, PI, RI, and placentome size (P ≥ 0.57). There was a parity-by-day interaction (P < 0.05) for RI, but UBF was not affected by parity or diet. After realimentation, there was no effect of treatment on ultrasound measurements in both experiments. At birth, lambs and placental measurements were not different (P ≥ 0.43). Restriction from days 50 to 90 does not seem to influence umbilical hemodynamics or conceptus growth in adult white face sheep, regardless of parity.
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Rabe H, Mercer J, Erickson-Owens D. What does the evidence tell us? Revisiting optimal cord management at the time of birth. Eur J Pediatr 2022; 181:1797-1807. [PMID: 35112135 PMCID: PMC9056455 DOI: 10.1007/s00431-022-04395-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 01/12/2022] [Accepted: 01/22/2022] [Indexed: 01/11/2023]
Abstract
A newborn who receives a placental transfusion at birth from delayed cord clamping (DCC) obtains about 30% more blood volume than those with immediate cord clamping (ICC). Benefits for term neonates include higher hemoglobin levels, less iron deficiency in infancy, improved myelination out to 12 months, and better motor and social development at 4 years of age especially in boys. For preterm infants, benefits include less intraventricular hemorrhage, fewer gastrointestinal issues, lower transfusion requirements, and less mortality in the neonatal intensive care unit by 30%. Ventilation before clamping the umbilical cord can reduce large swings in cardiovascular function and help to stabilize the neonate. Hypovolemia, often associated with nuchal cord or shoulder dystocia, may lead to an inflammatory cascade and subsequent ischemic injury. A sudden unexpected neonatal asystole at birth may occur from severe hypovolemia. The restoration of blood volume is an important action to protect the hearts and brains of neonates. Currently, protocols for resuscitation call for ICC. However, receiving an adequate blood volume via placental transfusion may be protective for distressed neonates as it prevents hypovolemia and supports optimal perfusion to all organs. Bringing the resuscitation to the mother's bedside is a novel concept and supports an intact umbilical cord. When one cannot wait, cord milking several times can be done quickly within the resuscitation guidelines. Cord blood gases can be collected with optimal cord management. Conclusion: Adopting a policy for resuscitation with an intact cord in a hospital setting takes a coordinated effort and requires teamwork by obstetrics, pediatrics, midwifery, and nursing.
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Affiliation(s)
- Heike Rabe
- Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | - Judith Mercer
- Neonatal Research Institute at Sharp Mary Birch Hospital for Women and Newborns, San Diego, CA USA
- College of Nursing, University of Rhode Island, Kingston, RI USA
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Faber JW, Buijtendijk MFJ, Klarenberg H, Vink AS, Coolen BF, Moorman AFM, Christoffels VM, Clur SA, Jensen B. Fetal Tricuspid Valve Agenesis/Atresia: Testing Predictions of the Embryonic Etiology. Pediatr Cardiol 2022; 43:796-806. [PMID: 34988599 DOI: 10.1007/s00246-021-02789-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 11/20/2021] [Indexed: 11/28/2022]
Abstract
Tricuspid valve agenesis/atresia (TVA) is a congenital cardiac malformation where the tricuspid valve is not formed. It is hypothesized that TVA results from a failure of the normal rightward expansion of the atrioventricular canal (AVC). We tested predictions of this hypothesis by morphometric analyses of the AVC in fetal hearts. We used high-resolution MRI and ultrasonography on a post-mortem fetal heart with TVA and with tricuspid valve stenosis (TVS) to validate the position of measurement landmarks that were to be applied to clinical echocardiograms. This revealed a much deeper right atrioventricular sulcus in TVA than in TVS. Subsequently, serial echocardiograms of in utero fetuses between 12 and 38 weeks of gestation were included (n = 23 TVA, n = 16 TVS, and n = 74 controls) to establish changes in AVC width and ventricular dimensions over time. Ventricular length and width and estimated fetal weight all increased significantly with age, irrespective of diagnosis. Heart rate did not differ between groups. However, in the second trimester, in TVA, the ratio of AVC to ventricular width was significantly lower compared to TVS and controls. This finding supports the hypothesis that TVA is due to a failed rightward expansion of the AVC. Notably, we found in the third trimester that the AVC to ventricular width normalized in TVA fetuses as their mitral valve area was greater than in controls. Hence, TVA associates with a quantifiable under-development of the AVC. This under-development is obscured in the third trimester, likely because of adaptational growth that allows for increased stroke volume of the left ventricle.
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Affiliation(s)
- Jaeike W Faber
- Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, 1105 AZ, Amsterdam, The Netherlands
| | - Marieke F J Buijtendijk
- Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, 1105 AZ, Amsterdam, The Netherlands
| | - Hugo Klarenberg
- Department of Biomedical Engineering & Physics, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Arja Suzanne Vink
- Department of Cardiology, Amsterdam University Medical Centres, Amsterdam, The Netherlands.,Department of Paediatric Cardiology, Emma Children's Hospital, Academic Medical Centre, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Bram F Coolen
- Department of Biomedical Engineering & Physics, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Antoon F M Moorman
- Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, 1105 AZ, Amsterdam, The Netherlands
| | - Vincent M Christoffels
- Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, 1105 AZ, Amsterdam, The Netherlands
| | - Sally-Ann Clur
- Department of Paediatric Cardiology, Emma Children's Hospital, Academic Medical Centre, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Bjarke Jensen
- Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centres, 1105 AZ, Amsterdam, The Netherlands.
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Blood Flow and Respiratory Gas Exchange in the Human Placenta at Term: A Data Update. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1395:379-384. [PMID: 36527666 DOI: 10.1007/978-3-031-14190-4_62] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Reliable measurements using modern techniques and consensus in experimental design have enabled the assessment of novel data sets for normal maternal and foetal respiratory physiology at term. These data sets include (a) principal factors affecting placental gas transfer, e.g., maternal blood flow through the intervillous space (IVS) (500 mL/min) and foeto-placental blood flow (480 mL/min), and (b) O2, CO2 and pH levels in the materno-placental and foeto-placental circulation. According to these data, the foetus is adapted to hypoxaemic hypoxia. Despite flat oxygen partial pressure (pO2) gradients between the blood of the IVS and the umbilical arteries of the foetus, adequate O2 delivery to the foetus is maintained by the higher O2 affinity of the foetal blood, high foetal haemoglobin (HbF) concentrations, the Bohr effect, the double-Bohr effect, and high foeto-placental (=umbilical) blood flow. Again, despite flat gradients, adequate CO2 removal from the foetus is maintained by a high diffusion capacity, high foeto-placental blood flow, the Haldane effect, and the double-Haldane effect. Placental respiratory gas exchange is perfusion-limited, rather than diffusion-limited, i.e., O2 uptake depends on O2 delivery.
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Cardiovascular fetal-to-neonatal transition: an in silico model. Pediatr Res 2022; 91:116-128. [PMID: 33731808 DOI: 10.1038/s41390-021-01401-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/16/2020] [Accepted: 01/21/2021] [Indexed: 11/09/2022]
Abstract
BACKGROUND Previous models describing the fetal-to-neonatal transition often lack oxygen saturation levels, homeostatic control mechanisms, phasic hemodynamic signals, or describe the heart with a time-varying elastance model. METHODS We incorporated these elements in the adapted CircAdapt model with the one-fiber model for myocardial contraction, to simulate the hemodynamics of the healthy term human fetal circulation and its transition during the first 24 h after birth. The fetal-to-neonatal model was controlled by a time- and event-based script of changes occurring at birth, such as lung aeration and umbilical cord clamping. Model parameters were based on and validated with human and animal data. RESULTS The fetal circulation showed low pulmonary blood flow, right ventricular dominance, and inverted mitral and tricuspid flow velocity patterns, as well as high mean ductus venosus flow velocity. The neonatal circulation showed oxygen saturation levels to gradually increase to 98% in the first 15 min after birth as well as temporary left ventricular volume overload. CONCLUSIONS Hemodynamics of the term fetus and 24-h-old neonate, as well as the events occurring directly after birth and the transition during the first 24 h after birth, were realistically represented, allowing the model to be used for educational purposes and future research. IMPACT With the addition of oxygen saturation levels, homeostatic pressure-flow control mechanisms, and the one-fiber model for myocardial contraction, a new closed-loop cardiovascular model was constructed to give more insight into the healthy term human fetal circulation and its cardiovascular transition during the first 24 h after birth. Extensive validation confirmed that the hemodynamics of the term fetus and the fetal-to-neonatal transition were realistically represented with the model. This well-validated and versatile model can serve as an education as well as a research platform for in silico investigation of fetal-to-neonatal hemodynamic changes under a wide range of physiological and pathophysiological conditions.
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Hemodynamic consequences of respiratory interventions in preterm infants. J Perinatol 2022; 42:1153-1160. [PMID: 35690691 PMCID: PMC9436777 DOI: 10.1038/s41372-022-01422-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 05/21/2022] [Accepted: 05/25/2022] [Indexed: 12/14/2022]
Abstract
Advances in perinatal management have led to improvements in survival rates for premature infants. It is known that the transitional period soon after birth, and the subsequent weeks, remain periods of rapid circulatory changes. Preterm infants, especially those born at the limits of viability, are susceptible to hemodynamic effects of routine respiratory care practices. In particular, the immature myocardium and cardiovascular system is developmentally vulnerable. Standard of care (but essential) respiratory interventions, administered as part of neonatal care, may negatively impact heart function and/or pulmonary or systemic hemodynamics. The available evidence regarding the hemodynamic impact of these respiratory practices is not well elucidated. Enhanced diagnostic precision and therapeutic judiciousness are warranted. In this narrative, we outline (1) the vulnerability of preterm infants to hemodynamic disturbances (2) the hemodynamic effects of common respiratory practices; including positive pressure ventilation and surfactant therapy, and (3) identify tools to assess cardiopulmonary interactions and guide management.
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Gonçalves FCLDSP, Lima MDC, Ximenes RADA, Miranda-Filho DDB, Martelli CMT, Rodrigues LC, Souza WVD, Lira PICD, Eickmann SH, Araújo TVB. A new insight into the definition of microcephaly in Zika congenital syndrome era. CAD SAUDE PUBLICA 2021; 37:e00228520. [PMID: 34852159 DOI: 10.1590/0102-311x00228520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 02/26/2021] [Indexed: 11/22/2022] Open
Abstract
This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika.
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Turkyilmaz G, Turkyilmaz S, Uygur L. Fetal cardiac alterations in the late-onset growth-restricted fetuses: A prospective case-control study. J Obstet Gynaecol Res 2021; 48:373-378. [PMID: 34841621 DOI: 10.1111/jog.15114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 10/14/2021] [Accepted: 11/22/2021] [Indexed: 11/28/2022]
Abstract
AIM Fetal growth restriction (FGR) has significant consequences on cardiac functions. This study aims to evaluate cardiac functional parameters in late-onset (FGR) fetuses and compare those appropriate for gestational age (AGA) fetuses. MATERIAL AND METHODS Fifty-six singleton pregnancies were involved in this prospective case-control study. Delphi consensus was used to define late-onset FGR. We compared the E/A ratio, left myocardial performance index (MPI) and tricuspid annular plane systolic excursion (TAPSE) in late-onset FGR cases and gestational age-matched AGA fetuses. RESULTS Twenty-eight late-onset FGR and 28 AGA fetuses were enrolled. The mean gestational age in the late-onset FGR group was 34.1 ± 2.3 weeks and 34.4 ± 2.1 in controls. The E/A ratio was 0.88 ± 0.09 in AGA fetuses, 0.79 ± 0.11 in the late-onset FGR group, and significantly lower in late-onset FGR fetuses (p: 0.012). Left MPI was 0.51 ± 0.09 in AGA and 0.62 ± 0.11 in the late-onset FGR group. Left MPI was markedly higher in late-onset FGR fetuses (p: 0.024). TAPSE was 7.4 ± 2.9 mm in controls and 5.2 ± 1.8 in the late-onset FGR group, and it was significantly shorter in the late-onset FGR fetuses (p: 0.016). CONCLUSION Late-onset FGR is associated with cardiac remodeling and dysfunction. Fetal echocardiography may be beneficial to detect those subtle cardiac changes.
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Affiliation(s)
- Gurcan Turkyilmaz
- Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, Van Education and Research Hospital, Van, Turkey
| | - Sebnem Turkyilmaz
- Department of Obstetrics and Gynecology, Van Education and Research Hospital, Van, Turkey
| | - Lutfiye Uygur
- Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, Zeynep Kamil Education and Research Hospital, Istanbul, Turkey
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Delivery room oxygen physiology and respiratory interventions for newborns with cyanotic congenital heart disease. J Perinatol 2021; 41:2309-2316. [PMID: 33758390 DOI: 10.1038/s41372-021-01029-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 02/07/2021] [Accepted: 02/19/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To characterize pulse oxygen saturation (SpO2) trajectories and respiratory interventions after birth for newborns with cyanotic congenital heart disease (CCHD). STUDY DESIGN Retrospective single-site study of newborns ≥32 weeks gestation with CCHD: single ventricle with critical aortic obstruction (SV-CAO), critical pulmonic obstruction (CPO), transposition of the great arteries (TGA). Minute-to-minute SpO2 values and respiratory interventions were summarized and compared. RESULTS Two hundred infants were enrolled. SpO2 at each minute differed across groups (p < 0.01), with the lowest values in TGA. All interventions were most frequent in TGA (p < 0.01). Continuous positive airway pressure was provided in 22% SV-CAO, 23% CPO, and 66% TGA. Positive pressure ventilation occurred in 7% SV-CAO, 14% CPO, and 33% TGA. Intubation occurred in 4% SV-CAO, 10% CPO, and 53% TGA. CONCLUSION We defined SpO2 trajectories and delivery room respiratory interventions for three CCHD phenotypes. These results inform delivery room management of these high-risk populations.
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Abstract
Understanding the perinatal cardiovascular physiology is essential for timely diagnosis and management of congenital heart defects (CHDs) in neonatal period. The incidence of CHDs is reported in 7 to 9 out of 1000 live births, with around 25% of them being critical congenital heart disease, defined as a congenital heart condition needing surgery/intervention or leading to death within 1 month after birth. Around 50% to 60% of the critical CHDs are detected on fetal anomaly screening. The signs and symptoms of critical congenital heart defects are often nonspecific during early neonatal period. The routine newborn physical examination often fails to detect many of these critical CHDs during the transitional circulation because of lack of signs soon after birth. While routine pulse oximetry screening typically performed at 24 to 48 hours after birth may help in detecting cyanotic heart conditions, noncyanotic CHDs such as coarctation of aorta may go undetected on pulse oximetry screening in asymptomatic infants. Some infants may deteriorate early while waiting for pulse oximetry screening, and this risk is much higher if the pulse oximetry screening is not performed to detect congenital heart conditions. There should be high degree of suspicion of critical CHDs in infants presenting with shock or hypoxia. Delay in diagnosis of CHDs has been reported to be associated with poor outcomes, and hence, it is extremely important to detect them in asymptomatic well-infants. Timely recognition and therapy with prostaglandin E1 infusion can be lifesaving in neonatal cardiac emergencies, and they should be urgently discussed with a pediatric cardiologist. This article reviews diagnosis and management of CHD in the delivery room and before surgery in the NICU.
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In vitro simulation of acute feto-fetal transfusion in case of single intrauterine fetal death in monochorionic twins. Placenta 2021; 111:26-32. [PMID: 34146967 DOI: 10.1016/j.placenta.2021.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/04/2021] [Accepted: 05/25/2021] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Thanks to shared circulation in monochorionic twins, single intrauterine fetal death (IUD) may lead to acute feto-fetal transfusion (aFFTR). The objective of the study was to describe our model of aFFTR simulation after IUD in monochorionic (MC) twins. METHODS Prospective study analyzed 99 fresh MC placentas with the physiological course. A specially designed protocol was used for the preparation and analysis of the placentas. A pair of infusion sets fixed together using a mechanical mercury sphygmomanometer cuff was connected to the cannulated umbilical arteries. The tonometer was pressurized up to 30 and 40 mmHg. A positive finding of aFFTR was determined as the amount exceeding 1 ml of dye flowed out of the umbilical cord simulating a dead fetus. The number and types of anastomoses, types, and distances between cords insertions, and the size of the placental areas for each fetus were also statistically analyzed. The placental angioarchitecture with and without proven aFFTR was statistically compared, odds ratio (OR) and multivariable logistic analysis were performed. RESULTS A total of 49/99 (49.5%) cases of aFFTR was proven, and the average transfusion time of 1 ml was 30 s (19-46 s). aFFTR was present in 49/78 (62.8%) of placentas with arterio-arterial (AA) anastomosis. The median diameter of AA anastomoses with the present, and absent aFFTRF was 2.0 mm and 1.0 mm, respectively. The proven interfetal transfusion was 8%, 31%, and 61% in AA anastomoses with a diameter below 0,5 mm, 0,5-1,5 mm, and above 1,5 mm, respectively (p < 0,001). AA anastomoses diameter >1.5 mm had OR of 44.2 (95% CI 5.54-352.39). In the case of coexistence of AA anastomosis and umbilical cord distance ≤5th percentile, the aFFTRF occurred in 90.9%. DISCUSSION The potential risk of aFFTR in monochorionic twins is mainly due to the presence and nature of AA anastomoses. The diameter and length of the vessels play a crucial role, which is clinically related to the distance of the umbilical cords insertions.
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Zidere V, Vigneswaran TV, Syngelaki A, Charakida M, Allan LD, Nicolaides KH, Simpson JM, Akolekar R. Reference Ranges for Pulsed-Wave Doppler of the Fetal Cardiac Inflow and Outflow Tracts from 13 to 36 Weeks' Gestation. J Am Soc Echocardiogr 2021; 34:1007-1016.e10. [PMID: 33957251 DOI: 10.1016/j.echo.2021.04.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 04/02/2021] [Accepted: 04/29/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Doppler assessment of ventricular filling and outflow tract velocities is an integral part of fetal echocardiography, to assess diastolic function, systolic function, and outflow tract obstruction. There is a paucity of prospective data from a large sample of normal fetuses in the published literature. The authors report reference ranges for pulsed-wave Doppler flow of the mitral valve, tricuspid valve, aortic valve, and pulmonary valve, as well as heart rate, in a large number of fetuses prospectively examined at a single tertiary fetal cardiology center. METHODS The study population comprised 7,885 fetuses at 13 to 36 weeks' gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective pulsed-wave Doppler blood flow measurements were taken of the mitral, tricuspid, aortic, and pulmonary valves. The fetal heart rate was recorded at the time of each assessment. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age. RESULTS The measurement for each cardiac Doppler measurement was expressed as a Z score (difference between observed and expected values divided by the fitted SD corrected for gestational age) and percentile. Analysis included calculation of gestation-specific SDs. Regression equations are provided for the cardiac inflow and outflow tracts. CONCLUSIONS This study establishes reference ranges for fetal cardiac Doppler measurements and heart rate between 13 to 36 weeks' gestation that may be useful in clinical practice.
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Affiliation(s)
- Vita Zidere
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; Department of Congenital Heart Disease, Evelina London Children's Hospital, Guy's & St Thomas' NHS Trust, London, United Kingdom.
| | - Trisha V Vigneswaran
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; Department of Congenital Heart Disease, Evelina London Children's Hospital, Guy's & St Thomas' NHS Trust, London, United Kingdom
| | - Argyro Syngelaki
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom
| | - Marietta Charakida
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; Department of Congenital Heart Disease, Evelina London Children's Hospital, Guy's & St Thomas' NHS Trust, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Lindsey D Allan
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom
| | - Kypros H Nicolaides
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom
| | - John M Simpson
- Harris Birthright Centre, Fetal Medicine Research Institute, King's College Hospital, London, United Kingdom; Department of Congenital Heart Disease, Evelina London Children's Hospital, Guy's & St Thomas' NHS Trust, London, United Kingdom
| | - Ranjit Akolekar
- Medway Fetal and Maternal Medicine Centre, Medway Maritime Hospital, Gillingham, United Kingdom; Institute of Medical Sciences, Canterbury Christ Church University, Chatham, United Kingdom
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Jagota D, George H, Walker M, Ravi Chandran A, Milligan N, Shinar S, Whitehead CL, Hobson SR, Serghides L, Parks WT, Baschat AA, Macgowan CK, Sled JG, Kingdom JC, Cahill LS. Sex differences in fetal Doppler parameters during gestation. Biol Sex Differ 2021; 12:26. [PMID: 33691774 PMCID: PMC7944891 DOI: 10.1186/s13293-021-00370-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/01/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Fetal sex is known to affect pregnancy outcomes. In current clinical practice, monitoring of fetal well-being is based on Doppler ultrasound measurements of major placental and fetal vessels. The objective of this study was to investigate the effect of fetal sex on Doppler parameters throughout gestation in healthy pregnancy. METHODS A prospective study was conducted in 240 pregnant women with ultrasound examinations at a 4-weekly interval between 12 and 38 weeks of gestation. Pulsed Doppler spectra were collected for the umbilical arteries (UAs), middle cerebral artery (MCA), descending abdominal aorta (DAo), and ductus venosus (DV). Linear mixed effects models were used to determine if the pulsatility indices (PIs) of these vessels depended on gestational age and fetal sex. RESULTS While there were no differences in the MCA PI and DV PIV over gestation between female and male fetuses, the trajectory of the UA and DAo PIs differed by fetal sex (p = 0.02 and p = 0.01, respectively). CONCLUSIONS Doppler ultrasound parameters were found to be dependent on fetal sex for some vessels and not for others in healthy pregnancies. Further investigations are needed to understand the physiological mechanisms for these sex differences and the relevance for disease processes in pregnancy.
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Affiliation(s)
- Dakshita Jagota
- Department of Chemistry, Memorial University of Newfoundland, 283 Prince Philip Drive, St. John's, NL, A1B 3X7, Canada
| | - Hannah George
- Department of Chemistry, Memorial University of Newfoundland, 283 Prince Philip Drive, St. John's, NL, A1B 3X7, Canada
| | - Melissa Walker
- Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
| | | | - Natasha Milligan
- Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
| | | | - Clare L Whitehead
- Pregnancy Research Centre, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Australia
| | | | - Lena Serghides
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
- Department of Immunology and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
- Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
| | - W Tony Parks
- Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Ahmet A Baschat
- Centre for Fetal Therapy, Johns Hopkins Medicine, Baltimore, MD, USA
| | - Christopher K Macgowan
- Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - John G Sled
- Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
- Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - John C Kingdom
- Mount Sinai Hospital, Toronto, Ontario, Canada
- Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
| | - Lindsay S Cahill
- Department of Chemistry, Memorial University of Newfoundland, 283 Prince Philip Drive, St. John's, NL, A1B 3X7, Canada.
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41
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Mandell E, Kinsella JP, Abman SH. Persistent pulmonary hypertension of the newborn. Pediatr Pulmonol 2021; 56:661-669. [PMID: 32930508 DOI: 10.1002/ppul.25073] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 09/09/2020] [Accepted: 09/10/2020] [Indexed: 11/07/2022]
Abstract
Persistent pulmonary hypertension of the newborn (PPHN) is a significant clinical problem characterized by refractory and severe hypoxemia secondary to elevated pulmonary vascular resistance resulting in right-to-left extrapulmonary shunting of deoxygenated blood. PPHN is associated with diverse cardiopulmonary disorders and a high early mortality rate for infants with severe PPHN. Surviving infants with PPHN have an increased risk of long-term morbidities. PPHN physiology can be categorized by (1) maladaptation: pulmonary vessels have normal structure and number but have abnormal vasoreactivity; (2) excessive muscularization: increased smooth muscle cell thickness and increased distal extension of muscle to vessels that are usually not muscularized; and (3) underdevelopment: lung hypoplasia associated with decreased pulmonary artery number. Treatment involves adequate lung recruitment, optimization of cardiac output and left ventricular function, and pulmonary vasodilators such as inhaled nitric oxide. Infants who fail to respond to conventional therapy should be evaluated for lethal lung disorders including alveolar-capillary dysplasia, T-box transcription factor 4 gene, thyroid transcription factor-1, ATP-binding cassette A3 gene, and surfactant protein diseases.
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Affiliation(s)
- Erica Mandell
- Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
- Section of Neonatology, Department of Pediatrics, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - John P Kinsella
- Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
- Section of Neonatology, Department of Pediatrics, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
| | - Steven H Abman
- Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
- Section of Pulmonary Medicine, Department of Pediatrics, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
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42
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Bertulli L, Robert T. Embryological development of the human cranio-facial arterial system: a pictorial review. Surg Radiol Anat 2021; 43:961-973. [PMID: 33492439 PMCID: PMC8164624 DOI: 10.1007/s00276-021-02684-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 01/07/2021] [Indexed: 12/14/2022]
Abstract
The embryological development of the cerebral vasculature is very complex. Historical and also more recent studies based on human embryos, comparative anatomy and cerebral angiographies allowed us to better understand this vasculature development. The knowledge and understanding of such embryological development are important for physicians interested in neurovascular pathologies. Indeed, all vascular variants and almost all vascular pathologies, such as aneurysms, dolichoectasia, atherosclerosis, and neurovascular conflicts could be explained by an alteration during the embryological life. There are also many variants of these vascular structures present in normal developed adults, which are variably associated with pathological entities. Understanding the process which leads to the development of the normal cerebral arterial system in humans is, therefore, very important to have a better knowledge of the possible clinical and surgical implications of these anomalies. In this paper, we review the embryological development of the cranio-facial arterial vasculature from its beginning at approximately days 21–50 of intrauterine life, with pictures illustrating each developmental phase.
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Affiliation(s)
- Lorenzo Bertulli
- Department of Neurosurgery, Neurocenter of the Southern Switzerland, Via Tesserete 46, 6903, Lugano, TI, Switzerland.
| | - Thomas Robert
- Department of Neurosurgery, Neurocenter of the Southern Switzerland, Via Tesserete 46, 6903, Lugano, TI, Switzerland
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Abduljalil K, Pan X, Clayton R, Johnson TN, Jamei M. Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Cardiac Output and Its Distribution to Different Organs during Development. Clin Pharmacokinet 2021; 60:741-757. [PMID: 33486719 DOI: 10.1007/s40262-020-00973-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND OBJECTIVE Fetal circulation is unique and the parameters describing hemodynamic status during development are critical for constructing a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of circulatory changes during fetal development, with a specific focus on developing these models, has not been reported. The objective of this work was to collate, analyze, and mathematically describe physiological information on fetal cardiac output and tissue blood flows during development. METHODS A comprehensive literature search was carried out to collate and evaluate the changes to fetal cardiac output and fetal tissue blood flows during growth. The collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing the average parameter changes and variability during development. RESULTS Data were available for fetal cardiac output (14 Doppler studies), blood flow through the fetal umbilical vein (15 studies), ductus venosus (6 studies), liver veins (5 studies), brain (4 studies), lungs (5 studies), and kidneys (2 studies). Fetal cardiac output is described as either an age- or weight-dependent function. The latter is preferred as it generates an individualized cardiac output that is correlated to the fetal body weight. Blood flow as a proportion of fetal cardiac output to the liver, placenta, brain, kidneys, and lungs was age varying, whilst for the adipose, bone, heart, muscle, and skin the blood flow proportions were fixed. The pattern of change (with respect to direction and pace) for each of these parameters was different. CONCLUSIONS Despite limitations in the availability of some values, the collected data provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications of these data include predicting xenobiotic exposure and risk assessment in the fetus following the administration of maternally dosed drugs or unintended exposure to environmental toxicants.
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Affiliation(s)
- Khaled Abduljalil
- Certara UK Limited (Simcyp Division), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK.
| | - Xian Pan
- Certara UK Limited (Simcyp Division), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK
| | - Ruth Clayton
- Certara UK Limited (Simcyp Division), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK
| | - Trevor N Johnson
- Certara UK Limited (Simcyp Division), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK
| | - Masoud Jamei
- Certara UK Limited (Simcyp Division), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK
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McHugh A, El-Khuffash A, Franklin O, Breathnach FM. Calling into question the future of hyperoxygenation in pregnancy. Eur J Obstet Gynecol Reprod Biol 2020; 258:93-97. [PMID: 33421817 DOI: 10.1016/j.ejogrb.2020.12.054] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 12/09/2020] [Accepted: 12/28/2020] [Indexed: 01/07/2023]
Abstract
Maternal hyperoxygenation has been investigated as a potential diagnostic and therapeutic tool since the 1960s. Since then, it has been applied in many obstetric scenarios, both clinically and in the research setting. It is often administered without any determination of pre-hyperoxygenation maternal or fetal oxygen levels. Studies focussing on maternal oxygen therapy for the treatment of fetal growth restriction have been ongoing for over thirty years and there remains no clear evidence of benefit. Studies investigating the potential diagnostic or therapeutic role of maternal oxygen therapy in the setting of fetal congenital cardiac disease have reported varying success rates and some potentially worrying adverse effects. The purpose of this article is to review the effects of maternal hyperoxygenation on fetal and maternal health and to ascertain the safety of undertaking further clinical trials that employ the use of hyperoxygenation in pregnancy.
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Affiliation(s)
- Ann McHugh
- Department of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Ireland.
| | - Afif El-Khuffash
- Department of Neonatology, Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Ireland
| | - Orla Franklin
- Children's Health Ireland at Crumlin, Dublin, Ireland
| | - Fionnuala M Breathnach
- Department of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland, Rotunda Hospital, Dublin, Ireland
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Biswas A, Mankad K, Shroff M, Hanagandi P, Krishnan P. Neuroimaging Perspectives of Perinatal Arterial Ischemic Stroke. Pediatr Neurol 2020; 113:56-65. [PMID: 33038575 DOI: 10.1016/j.pediatrneurol.2020.08.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/24/2020] [Accepted: 08/18/2020] [Indexed: 11/26/2022]
Abstract
Perinatal stroke ranks second only to that of adult stroke in the overall stroke incidence. It is a major contributor to long-term neurological morbidity, which includes cognitive dysfunction, cerebral palsy and seizures. Risk factors for stroke in the perinatal period differ from those in children and tend to be multifactorial. Differences in territorial predilection, response to injury, and stroke evolution exist when compared with childhood and adult stroke, and also among differing gestation age groups in the perinatal period (i.e., extreme preterm versus preterm versus term). The role of imaging is to diagnose stroke, exclude stroke mimics, establish the nature of stroke (arterial versus venous), and aid in prognostication. Magnetic resonance imaging is the mainstay of neuroimaging in perinatal stroke. Advanced imaging techniques such as diffusion tensor imaging and perfusion-weighted imaging are emerging as useful supplements to conventional imaging sequences. Here we describe the neuroimaging of perinatal arterial ischemic stroke with emphasis on imaging techniques, imaging phenotypes, stroke evolution, role of advanced imaging, and differences between stroke in preterm and term neonates. We also briefly describe the emerging role of fetal magnetic resonance imaging in the diagnosis of in utero stroke.
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Affiliation(s)
- Asthik Biswas
- Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Kshitij Mankad
- Department of Radiology, Great Ormond Street Hospital NHS Foundation Trust, London, UK
| | - Manohar Shroff
- Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Prasad Hanagandi
- Department of Medical Imaging, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Pradeep Krishnan
- Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, Canada
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Rykiel G, López CS, Riesterer JL, Fries I, Deosthali S, Courchaine K, Maloyan A, Thornburg K, Rugonyi S. Multiscale cardiac imaging spanning the whole heart and its internal cellular architecture in a small animal model. eLife 2020; 9:e58138. [PMID: 33078706 PMCID: PMC7595733 DOI: 10.7554/elife.58138] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 10/09/2020] [Indexed: 12/18/2022] Open
Abstract
Cardiac pumping depends on the morphological structure of the heart, but also on its subcellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized ultrastructural disruptions that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three-dimensional (3D) heart structure, to assess malformations; and its ultrastructure, to assess organelle disruptions. We present here a multiscale, correlative imaging procedure that achieves high-resolution images of the whole heart, using 3D micro-computed tomography (micro-CT); and its ultrastructure, using 3D scanning electron microscopy (SEM). In a small animal model (chicken embryo), we achieved uniform fixation and staining of the whole heart, without losing ultrastructural preservation on the same sample, enabling correlative multiscale imaging. Our approach enables multiscale studies in models of congenital heart disease and beyond.
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Affiliation(s)
- Graham Rykiel
- Biomedical Engineering, Oregon Health & Science UniversityPortlandUnited States
| | - Claudia S López
- Biomedical Engineering, Oregon Health & Science UniversityPortlandUnited States
- Multiscale Microscopy Core, Oregon Health & Science UniversityPortlandUnited States
| | - Jessica L Riesterer
- Biomedical Engineering, Oregon Health & Science UniversityPortlandUnited States
- Multiscale Microscopy Core, Oregon Health & Science UniversityPortlandUnited States
| | - Ian Fries
- Biomedical Engineering, Oregon Health & Science UniversityPortlandUnited States
| | - Sanika Deosthali
- Biomedical Engineering, Oregon Health & Science UniversityPortlandUnited States
| | | | - Alina Maloyan
- Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health & Science UniversityPortlandUnited States
| | - Kent Thornburg
- Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health & Science UniversityPortlandUnited States
| | - Sandra Rugonyi
- Biomedical Engineering, Oregon Health & Science UniversityPortlandUnited States
- Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health & Science UniversityPortlandUnited States
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OʼBrien-Abel N. Clinical Implications of Fetal Heart Rate Interpretation Based on Underlying Physiology. MCN Am J Matern Child Nurs 2020; 45:82-91. [PMID: 31714283 DOI: 10.1097/nmc.0000000000000596] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Understanding the physiology of fetal oxygenation and various influences on fetal heart rate control supports nurses, midwives, and physicians in interpreting and managing electronic fetal heart rate tracings during labor and birth. Maternal oxygenation, placental circulation and exchange, umbilical blood flow and fetal circulation affect fetal oxygenation, which is reflected in observed fetal heart rate patterns. Fetal heart control is further influenced by the central and autonomic nervous systems, baroreceptors, chemoreceptors, humoral factors, sleep-wake patterns, breathing movements, medications, painful stimuli, sound and vibrations, and temperature. Knowledge of the physiologic basis for fetal heart rate pattern characteristics guides interventions to improve fetal oxygenation when indicated. A review and update on clinical implications of fetal heart rate pattern interpretation based on underlying physiology is presented.
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Affiliation(s)
- Nancy OʼBrien-Abel
- Nancy O'Brien-Abel is a Perinatal Clinical Nurse Specialist, Perinatal Consulting, LLC, Affiliate Instructor, School of Nursing, University of Washington, Seattle, WA. The author can be reached via e-mail at
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48
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Soares-da-Silva F, Peixoto M, Cumano A, Pinto-do-Ó P. Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development. Front Cell Dev Biol 2020; 8:612. [PMID: 32793589 PMCID: PMC7387668 DOI: 10.3389/fcell.2020.00612] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 06/19/2020] [Indexed: 12/14/2022] Open
Abstract
Hematopoietic stem cells (HSCs) generated during embryonic development are able to maintain hematopoiesis for the lifetime, producing all mature blood lineages. HSC transplantation is a widely used cell therapy intervention in the treatment of hematologic, autoimmune and genetic disorders. Its use, however, is hampered by the inability to expand HSCs ex vivo, urging for a better understanding of the mechanisms regulating their physiological expansion. In the adult, HSCs reside in the bone marrow, in specific microenvironments that support stem cell maintenance and differentiation. Conversely, while developing, HSCs are transiently present in the fetal liver, the major hematopoietic site in the embryo, where they expand. Deeper insights on the dynamics of fetal liver composition along development, and on how these different cell types impact hematopoiesis, are needed. Both, the hematopoietic and hepatic fetal systems have been extensively studied, albeit independently. This review aims to explore their concurrent establishment and evaluate to what degree they may cross modulate their respective development. As insights on the molecular networks that govern physiological HSC expansion accumulate, it is foreseeable that strategies to enhance HSC proliferation will be improved.
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Affiliation(s)
- Francisca Soares-da-Silva
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
- Lymphocytes and Immunity Unit, Immunology Department, Pasteur Institute, Paris, France
- INSERM U1223, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Márcia Peixoto
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
- Lymphocytes and Immunity Unit, Immunology Department, Pasteur Institute, Paris, France
- INSERM U1223, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Ana Cumano
- Lymphocytes and Immunity Unit, Immunology Department, Pasteur Institute, Paris, France
- INSERM U1223, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Perpetua Pinto-do-Ó
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
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Viggiano M, Vassallo C, Massolo AC, Vicario R, Romiti A, Caforio L, Bagolan P. Physiological changes in cardiac dimensions and function in low-risk pregnancies. J Matern Fetal Neonatal Med 2020; 35:2407-2410. [PMID: 32611213 DOI: 10.1080/14767058.2020.1786057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Milena Viggiano
- Fetal Medicine and Surgery Unit, Piazza Sant'Onofrio, Ospedale Pediatrico Bambino Gesu, Roma, Italy
| | - Chiara Vassallo
- Ospedale Pediatrico Bambino Gesù, Roma, Italy.,Policlinico Universitario Agostino Gemelli, Roma, Italy
| | | | | | - Anita Romiti
- Fetal Medicine and Surgery Unit, Piazza Sant'Onofrio, Ospedale Pediatrico Bambino Gesu, Roma, Italy
| | | | - Pietro Bagolan
- Newborn Surgery Unit, Ospedale Pediatrico Bambino Gesu, Roma, Italy
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50
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We have all been on ECMO: The cues we can take from fetal circulation. CIRUGIA CARDIOVASCULAR 2020. [DOI: 10.1016/j.circv.2020.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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