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      Fetal Diagnosis and Therapy during the COVID-19 Pandemic: Guidance on Behalf of the International Fetal Medicine and Surgery Society

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          Abstract

          The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother's preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates.

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          Most cited references 31

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          Coronavirus disease (COVID‐19) and neonate: What neonatologist need to know

           Qi Lu,  Yuan Shi (2020)
          Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS‐CoV‐2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID‐19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID‐19 infection in newborns and children.
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            What are the risks of COVID-19 infection in pregnant women?

             Jie Qiao (2020)
            Since December, 2019, the outbreak of the 2019 novel coronavirus disease (COVID-19) infection has become a major epidemic threat in China. As of Feb 11, 2020, the cumulative number of confirmed cases in mainland China has reached 38 800, with 4740 (12·2%) cured cases and 1113 (2·9%) deaths; additionally, there have been 16 067 suspected cases so far. 1 All 31 provinces in mainland China have now adopted the first-level response to major public health emergencies. The National Health Commission of China has published a series of guidelines on the prevention, diagnosis, and treatment of COVID-19 pneumonia, based on growing evidence of the pathogens responsible for COVID-19 infection, as well as the epidemiological characteristics, clinical features, and the most effective treatments.2, 3, 4 The central government and some provincial governments have provided food and medical supplies and dispatched expert groups and medical teams to manage and control the outbreak response in the hardest-hit areas (Wuhan and neighbouring cities in Hubei province). As the COVID-19 outbreak unfolds, prevention and control of COVID-19 infection among pregnant women and the potential risk of vertical transmission have become a major concern. More evidence is needed to develop effective preventive and clinical strategies. The latest research by Huijun Chen and colleagues 5 reported in The Lancet provides some insight into the clinical characteristics, pregnancy outcomes, and vertical transmission potential of COVID-19 infection in pregnant women. Although the study analysed only a small number of cases (nine women with confirmed COVID-19 pneumonia), under such emergent circumstances these findings are valuable for preventive and clinical practice in China and elsewhere. Although neonatal nasopharyngeal swab samples have been collected in some hospitals across China, this study also collected and tested amniotic fluid, cord blood, and breastmilk samples for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus allowing a more detailed assessment of the vertical transmission potential of COVID-19 infection. SARS-CoV-2 is a new strain of coronaviruses that are pathogenic to humans. Another two notable strains are SARS-CoV and the Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). A study done by Roujian Lu and colleagues 6 found that although SARS-CoV-2 is genetically closer to two bat-derived SARS-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21 (with about 88% genome sequence identity), than to SARS-CoV-1 (about 79% identity) and MERS-CoV (about 50% identity), homology modelling has revealed that SARS-CoV-2 has a similar receptor-binding domain structure to that of SARS-CoV-1, which suggests that COVID-19 infection might have a similar pathogenesis to SARS-CoV-1 infection.6, 7, 8 Thus, the risk of vertical transmission of COVID-19 might be as low as that of SARS-CoV-1. The present study by Chen and colleagues did not find any evidence of the presence of SARS-CoV-2 viral particles in the products of conception or in neonates, in accordance with the findings of a previous study on SARS-CoV-1 done by Wong and colleagues. 9 Two neonatal cases of COVID-19 infection have been confirmed so far, 10 with one case confirmed at 17 days after birth and having a close contact history with two confirmed cases (the baby's mother and maternity matron) and the other case confirmed at 36 h after birth and for whom the possibility of close contact history cannot be excluded. However, no reliable evidence is as yet available to support the possibility of vertical transmission of COVID-19 infection from the mother to the baby. © 2020 Soe Zeya Tun/Reuters 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Previous studies have shown that SARS during pregnancy is associated with a high incidence of adverse maternal and neonatal complications, such as spontaneous miscarriage, preterm delivery, intrauterine growth restriction, application of endotracheal intubation, admission to the intensive care unit, renal failure, and disseminated intravascular coagulopathy.9, 11 However, pregnant women with COVID-19 infection in the present study had fewer adverse maternal and neonatal complications and outcomes than would be anticipated for those with SARS-CoV-1 infection. Although a small number of cases was analysed and the findings should be interpreted with caution, the findings are mostly consistent with the clinical analysis done by Zhu and colleagues 12 of ten neonates born to mothers with COVID-19 pneumonia. The clinical characteristics reported in pregnant women with confirmed COVID-19 infection are similar to those reported for non-pregnant adults with confirmed COVID-19 infection in the general population and are indicative of a relatively optimistic clinical course and outcomes for COVID-19 infection compared with SARS-CoV-1 infection.13, 14 Nonetheless, because of the small number of cases analysed and the short duration of the study period, more follow-up studies should be done to further evaluate the safety and health of pregnant women and newborn babies who develop COVID-19 infection. As discussed in the study, pregnant women are susceptible to respiratory pathogens and to development of severe pneumonia, which possibly makes them more susceptible to COVID-19 infection than the general population, especially if they have chronic diseases or maternal complications. Therefore, pregnant women and newborn babies should be considered key at-risk populations in strategies focusing on prevention and management of COVID-19 infection. Based on evidence from the latest studies and expert recommendations, as well as previous experiences from the prevention and control of SARS, the National Health Commission of China launched a new notice on Feb 8, 2020, 15 which proposed strengthening health counselling, screening, and follow-ups for pregnant women, reinforcing visit time and procedures in obstetric clinics and units with specialised infection control preparations and protective clothing, and emphasised that neonates of pregnant women with suspected or confirmed COVID-19 infection should be isolated in a designated unit for at least 14 days after birth and should not be breastfed, to avoid close contact with the mother while she has suspected or confirmed COVID-19 infection. We need to further strengthen our capacity to deal with emergent infectious disease outbreaks, through laws and regulations to prevent and control the spread of infectious diseases and to avoid outbreak clusters in families, communities, and other public places, and to do so with transparency and solidarity. Timely reporting and disclosure of emergent infectious diseases is also important to avoid delayed responses. Infection control and management procedures in hospitals and other places with several confirmed cases isolated together should also be maintained, and specialised clothing and equipment provided to protect medical professionals and other health workers from occupational exposure to COVID-19 infection.
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              Expert consensus for managing pregnant women and neonates born to mothers with suspected or confirmed novel coronavirus (COVID-19) infection

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                Author and article information

                Journal
                Fetal Diagn Ther
                Fetal. Diagn. Ther
                FDT
                Fetal Diagnosis and Therapy
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1015-3837
                1421-9964
                6 May 2020
                : 1-10
                Affiliations
                aDepartment of Obstetrics and Gynecology, UZ Leuven, Leuven, Belgium
                bDepartment of Development and Regeneration, KU Leuven, Leuven, Belgium
                cInstitute for Women's Health, University College London, London, United Kingdom
                dDepartment of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
                eZucker School of Medicine at Hofstra/Northwell − Lenox Hill Hospital, New York, New York, USA
                fDepartment of Surgery, UC Davis School of Medicine, Sacramento, California, USA
                gDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
                hClinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, UZ Leuven, Leuven, Belgium
                iDivision of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
                jDepartment of Anesthesiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA
                kDepartment of Obstetrics and Gynecology, Maternal Fetal Medicine, Columbia University, New York, New York, USA
                lFetal Medicine Unit, Ontario Fetal Centre, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
                mUC Davis Children's Hospital, Sacramento, California, USA
                Author notes
                *Jan Deprest, Department of Obstetrics and Gynecology, UZ Leuven − Campus Gasthuisberg, Herestraat 49, BE–3000 Leuven (Belgium), jan.deprest@ 123456uzleuven.be
                Article
                fdt-0001
                10.1159/000508254
                7251580
                32375144
                Copyright © 2020 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                Page count
                Tables: 2, References: 68, Pages: 10
                Categories
                Original Paper

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