Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications. Â© 2020, Â© 2020 Taylor & Francis Group, LLC

Abbasi, H.

Bahrami, R.

Behforouz, A.

Dastgheib, S.A.

Ferdosian, F.

Karimi-Zarchi, M.

Mirjalili, S.R.

Neamatzadeh, H.

eprints Iran University of Medical Sciences

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/340385687Vertical Transmission of Coronavirus Disease 19 (COVID-19) fromInfected Pregnant Mothers to Neonates: A ReviewArticle  in  Fetal and pediatric pathology · April 2020DOI: 10.1080/15513815.2020.1747120CITATIONS75READS3,2058 authors, including:Some of the authors of this publication are also working on these related projects:meta analyes project View projectResearcher (HO Center) View projectMojgan Karimi-ZarchiShahid Sadoughi University of Medical Sciences and Health Services125 PUBLICATIONS   1,191 CITATIONS   SEE PROFILEHossein NeamatzadehShahid Sadoughi University of Medical Sciences and Health Services137 PUBLICATIONS   947 CITATIONS   SEE PROFILEAlireza DastgheibShiraz University of Medical Sciences36 PUBLICATIONS   138 CITATIONS   SEE PROFILEHajar AbbasiShahid Beheshti University of Medical Sciences14 PUBLICATIONS   94 CITATIONS   SEE PROFILEAll content following this page was uploaded by Hossein Neamatzadeh on 02 April 2020.The user has requested enhancement of the downloaded file.REVIEWVertical Transmission of Coronavirus Disease 19 (COVID-19)from Infected Pregnant Mothers to Neonates: A ReviewMojgan Karimi-Zarchia,b, Hossein Neamatzadehc,d, Seyed Alireza Dastgheibe, HajarAbbasif, Seyed Reza Mirjalilid,g, Athena Behforouzf, Farzad Ferdosiang,h, andReza BahramiiaDepartment of Obstetrics and Gynecology, Iran University of Medical Sciences, Tehran, Iran;bEndometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran; cDepartment ofMedical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; dMother and NewbornResearch Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; eDepartment of MedicalGenetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; fDepartment ofObstetrics and Gynecology, Shahid Beheshti University of Medical Sciences, Tehran, Iran; gDepartmentof Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; hChildren Growth DisorderResearch Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; iNeonatal Research Center,Shiraz University of Medical Sciences, Shiraz, IranABSTRACTBackground: Since early December 2019, the Coronavirus Disease19 (COVID-19) infection has been prevalent in China and eventuallyspread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may beat risk of congenital COVID-19. Methods: We reviewed the risk ofvertical transmission of COVID-19 to the fetus of infected mothers byusing data of published articles or official websites up to March 4,2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neo-nates or placentas. Two mothers died from COVID-19-related respira-tory complications after delivery. Conclusions: Currently, based onlimited data, there is no evidence for intrauterine transmission ofCOVID-19 from infected pregnant women to their fetuses. Mothersmay be at increased risk for more severe respiratory complications.ARTICLE HISTORYReceived 4 March 2020Revised 18 March 2020Accepted 20 March 2020KEYWORDSCorona Virus; COVID-19;vertical transmission;placenta; pregnantmothers; neonateIntroductionThe novel coronavirus was first detected in Wuhan City, the capital of Hubei Province,with a population of 11 million [1]. During the first weeks of January 2019, theCOVID-19 virus spread rapidly to other countries including Thailand, Japan, Korea,United States, and Iran [2]. On 7 January 2020 scientists in China identified the etio-logical agent of the epidemic as a previously unknown coronavirus, and it was given thedesignation 2019-nCoV (for 2019 novel coronavirus) [3,4]. On February 11, 2020, thenovel coronavirus disease received an official name by the World Health Organization(WHO), Coronavirus Disease 19 (COVID-19), [5] and the International Committee onCONTACT Seyed Alireza Dastgheib dastgheibsa@gmail.com Department of Medical Genetics, School ofMedicine, Shiraz University of Medical Sciences, Shiraz, Iran; Hajar Abbasi haabbasi65@gmail.com Department ofObstetrics and Gynecology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2020 Taylor & Francis Group, LLCFETAL AND PEDIATRIC PATHOLOGYhttps://doi.org/10.1080/15513815.2020.1747120Taxonomy of Viruses has proposed SARS-CoV-2 as the name of the virus that causesCOVID-19 [6]. The most common manifestations of COVID-19 consist of fever, cough,and fatigue or myalgia, sputum production, and headache [4,7,8].Viral pneumonia is an important cause of morbidity and mortality among pregnantwomen [9]. Maternal pneumonias are associated with several adverse obstetrical out-comes, including premature rupture of membranes (PROM) and preterm labor (PTL),intrauterine fetal demise (IUFD), intrauterine growth restriction (IUGR), and neonataldeath [3]. Since the emergence of a coronavirus not previously seen in humans, there islittle data on adverse pregnancy outcomes in pregnant women with COVID-19.Coronaviruses are single-stranded RNA, non-segmented, enveloped viruses, which causeillness ranging in severity from the common cold to severe and fatal illness. Limitedadverse infant outcomes (e.g., miscarriage and stillbirth) have been reported amonginfants. However, it is not evident that these outcomes were related to maternal infec-tion, and at this time the risk of adverse infant outcomes is not known. Data from pre-vious coronaviruses (SARS-CoV and MERS-CoV) suggests that pregnant women maybe at higher risk of severe illness, morbidity, or mortality compared with the generalpopulation. At this time, very little is known about COVID-19, particularly related toits effect on pregnant women and infants, and there currently are no recommendationsspecific to pregnant women regarding the evaluation or management of COVID-19.The Centers for Disease Control and Prevention (CDC) has developed InterimGuidance on Breastfeeding for a Mother Confirmed or Under Investigation forCOVID-19 [10]. Currently, it is not known whether COVID-19 virus can be transmit-ted through breast milk, but it is well known that an infected mother can transmit thevirus through respiratory droplets during breastfeeding [1].COVID-19As COVID-19 virus is still spreading, more infections in pregnant women are likely tobe seen. Whether COVID-19 increases the risk of miscarriage, stillbirth, preterm deliv-ery, fetal tachycardia and fetal distress is unknown. According to the official website ofMinistry of Health and Medical Education (MOHME) in Mazandaran and Zanjan prov-inces, Iran, three infants were born from infected pregnant mothers. Among these threecases of COVID-19 infection there were two mothers who developed acute respiratorydistress syndrome (ARDS) after delivery and died. According to the websites, their neo-nates were negative when tested for COVID-19 [11]. It seems that COVID-19 infectionin pregnant patients may increase the risk of maternal mortality. Chen et al., reportedthe clinical characteristics and placental pathology from three women with confirmedCOVID-19 infection. No COVID-19 nucleic acid was detected in the placentas or neo-natal throat swabs by RT-PCR. Moreover, they found that the clinical characteristics ofinfected pregnant women in late pregnancy were similar to those of non-pregnantpatients, and no severe adverse pregnancy outcome was found in the three cases [12].In other study, Chen et al., evaluated clinical records, laboratory results, and chest com-puted tomography (CT) scans among nine pregnant women with laboratory-confirmedCOVID-19 who were referred to Zhongnan Hospital of Wuhan University, Wuhan,China, between January 20 and January 31, 2020. Their results revealed that the clinical2 M. KARIMI-ZARCHI ET AL.characteristics of COVID-19 in pregnant women were similar to infected non-pregnantwomen. They reported nine livebirths and none of the patients developed severeCOVID-19 or died, and all samples tested negative for the virus in neonates. Their find-ings supported that there is currently no evidence for vertical transmission in infectedmothers in late pregnancy [13]. In a retrospective study, Zhang et al., evaluated theeffect of COVID-19 on pregnancy outcomes and neonatal prognosis between 16infected women with COVID-19 and 45 women without COVID-19 women undergoingcesarean section (CS) in Hubei Province. There were no significant differences in fetaldistress, meconium-stained amniotic fluid, preterm delivery, and neonatal asphyxiabetween the two groups. They did not find 2019-nCoV infection in neonates deliveredfrom pregnant mothers with COVID-19. In the treatment of uterine contraction fatigue,carbetocin or carboprost tromethamine was used more in CS for infected pregnantmothers compared to healthy mothers. They observed that timely termination of preg-nancy after 32–34weeks of pregnancy by CS was not associated with an increased riskof maternal complications in pregnant women with indications for obstetric surgery orcritical illness of COVID-19, but it was beneficial for the treatment and rehabilitation ofmaternal pneumonia [14].MERS-CoV or SARS-CoVStudies have not yet reported ongoing transmission of MERS-CoV or SARS-CoV withincommunities outside of health care settings. In 2004, Lam et al., in a case-control studyincluding 10 pregnant mothers infected by SARS-CoV and 40 non-pregnant womenwith SARS evaluated the clinical course and outcomes of pregnancy in women withsevere acute respiratory syndrome. Their results revealed that pregnancy appeared tohave no effect on clinical symptoms or time to presentation after symptom onset.However, complications and adverse outcomes including longer hospital stay, renal fail-ure, sepsis, and disseminated intravascular coagulopathy (DIC) in pregnant womenwere statistically significantly increased. They reported the need for mechanical ventila-tion and rate of mortality among them were more frequent than non-pregnant women[15]. Other studies in the USA, Canada and Hong Kong reported that these pregnantwomen required mechanical ventilation, hemodialysis due to acute renal failure, devel-oped seizures and positive cerebrospinal fluid for SARS-CoV more frequently [16,17].Those studies did not report any stillbirths among the infected mothers. According tothose studies all mothers recovered and their neonate’s tests for SARS-CoV RNA werenegative. In another study, Maxwell et al., reported that of seven pregnant mothersinfected with SARS-CoV at a designated SARS unit, two mothers died and four mothersrequired intensive care unit (ICU) hospitalization and mechanical ventilation. Twoinfected mothers recovered and maintained their pregnancy but had infants with intra-uterine growth restriction (IUGR). Among the live newborn infants, none had clinicalor laboratory evidence for SARS-CoV infection [18]. Ng et al., in a study evaluated theplacental pathology in seven pregnant women infected with SARS-CoV. In two womenwho were convalescing from SARS-CoV infection during the 1st trimester of pregnancy,the placentas were normal. In three mothers, the placentas demonstrated increasedFETAL AND PEDIATRIC PATHOLOGY 3subchorionic and intervillous fibrin, which could be associated with abnormal maternalblood flow to the placenta [19].ConclusionsLimited evidence exists on vertical transmission, prevalence and clinical features ofCOVID-19 during pregnancy, birth, and the postnatal period. Currently there was noevidence for intrauterine vertical transmission of COVID-19 from infected pregnantmothers to their fetuses. However, infected mothers may be at increased risk for moresevere respiratory complications. It is well known that an infected mother can transmitthe COVID-19 virus through respiratory droplets during breastfeeding. Thus, the moth-ers with known or suspected COVID-19 should adhere to standard and contact precau-tions during breastfeeding.AcknowledgmentsThe authors thank the editors and the anonymous reviewers for insightful suggestions onthis study.Disclosure statementNo potential conflict of interest was reported by the authors.References[1] Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ. Coronavirus Disease2019 (COVID-19) and pregnancy: what obstetricians need to know. Am J Obstet Gynecol.2020. pii: S0002-9378(20)30197-6. doi: 10.1016/j.ajog.2020.02.017. [Epub ahead of print].[2] Working Group for the Prevention and Control of Neonatal 2019-nCoV Infection in thePerinatal Period of the Editorial Committee of Chinese Journal of ContemporaryPediatrics. [Perinatal and neonatal management plan for prevention and control of 2019novel coronavirus infection (1st Edition)]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22:87–90.[3] Schwartz DA, Graham AL. Potential maternal and infant outcomes from (Wuhan)Coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and otherhuman coronavirus infections. Viruses. 2020;12(2):194. doi:10.3390/v12020.[4] Ma K, Chen T, Han MF, Guo W, Ning Q. [Management and clinical thinking ofCoronavirus Disease 2019]. Zhonghua Gan Zang Bing Za Zhi. 2020;28:E002. doi:10.3760/cma.j.issn.1007-3418.2020.0002.[5] World Health Organization. Coronavirus disease (COVID-19) outbreak; n.d. [accessed2020 Mar 4]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.[6] Gorbalenya AE. Severe acute respiratory syndrome-related coronavirus—the species andits viruses, a statement of the Coronavirus Study Group. BioRxiv 2020:2020.02.07.937862.doi:10.1101/2020.02.07.937862.[7] Zhu ZB, Zhong CK, Zhang KX, Dong C, Peng H, Xu T, Wang AL, Guo ZR, Zhang YH.[Epidemic trend of corona virus disease 2019 (COVID-19) in mainland China]. ZhonghuaYu Fang Yi Xue Za Zhi. 2020;54:E022. doi:10.3760/cma.j.cn112150-20200222-00163.[8] Yang HY, Duan GC. [Analysis on the epidemic factors for the corona virus disease].Zhonghua Yu Fang Yi Xue Za Zhi. 2020;54:E021. doi:10.3760/cma.j.cn112150-20200227-00196.4 M. KARIMI-ZARCHI ET AL.[9] Berkowitz K, LaSala A. Risk factors associated with the increasing prevalence of pneumo-nia during pregnancy. Am J Obstetr Gynecol. 1990;163:981–5. doi:10.1016/0002-9378(90)91109-p.[10] Centers for Disease Control and Prevention, National Center for Immunization andRespiratory Diseases. Interim infection prevention and control recommendations forpatients with confirmed 2019 novel coronavirus (2019-nCoV) or patients under investiga-tion for 2019-nCoV in healthcare settings. Centers for Disease Control and Prevention;2020 Feb 28 [accessed 2020 Mar 4]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clin-ical-guidance-management-patients.html.[11] Tasnim Agency. Birth of a neonate from infected mother COVID-19 in Babol city; 2020Mar 3 [Accessed 2020 Mar 4]. https://www.tasnimnews.com/fa/news/1398/12/14/2216407/.[12] Chen S, Huang B, Luo DJ, Li X, Yang F, Zhao Y, Nie X, Huang BX. [Pregnant womenwith new coronavirus infection: a clinical characteristics and placental pathological ana-lysis of three cases]. Zhonghua Bing Li Xue Za Zhi. 2020;49:E005. doi:10.3760/cma.j.cn112151-20200225-00138.[13] Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, Li J, Zhao D, Xu D, Gong Q, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infec-tion in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809–15. doi:10.1016/S0140-6736(20)30360-3.[14] Zhang L, Jiang Y, Wei M, Cheng BH, Zhou XC, Li J, Tian JH, Dong L, Hu RH. [Analysisof the pregnancy outcomes in pregnant women with COVID-19 in Hubei Province].Zhonghua Fu Chan Ke Za Zhi. 2020;55(0):E009. doi:10.3760/cma.j.cn112141-20200218-00111.[15] Lam CM, Wong SF, Leung TN, Chow KM, Yu WC, Wong TY, Lai ST, Ho LC. A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnantwomen with severe acute respiratory syndrome. BJOG. 2004;111:771–4. doi:10.1111/j.1471-0528.2004.00199.x.[16] Robertson CA, Lowther SA, Birch T, Tan C, Sorhage F, Stockman L, McDonald C,Lingappa JR, Bresnitz E. SARS and pregnancy: a case report. Emerg Infect Dis. 2004;10:345–8. doi:10.3201/eid1002.030736.[17] Yudin MH, Steele DM, Sgro MD, Read SE, Kopplin P, Gough KA. Severe acute respira-tory syndrome in pregnancy. Obstetr Gynecol. 2005;105:124–7. doi:10.1097/01.AOG.0000151598.49129.de.[18] Maxwell C, McGeer A, Tai KFY, Sermer M. No. 225-Management guidelines for obstetricpatients and neonates born to mothers with suspected or probable severe acute respiratorysyndrome (SARS). J Obstetr Gynaecol Can. 2017;39:e130–7. doi:10.1016/j.jogc.2017.04.024.[19] Ng PC, Leung CW, Chiu WK, Wong SF, Hon E. SARS in newborns and children. BiolNeonate. 2004;85:293–8. doi:10.1159/000078174.FETAL AND PEDIATRIC PATHOLOGY 5View publication stats

Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review

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Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review

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