Skip to main content

COVID-19 during pregnancy should we really worry from vertical transmission or rather from fetal hypoxia and placental insufficiency? A systematic review



COVID-19 is the largest outbreak to strike humanity. The wide scale of fatalities and morbidities lead to a concurrent pandemic of uncertainty in scientific evidence. Conflicting evidences are released on daily basis about the neonatal outcomes of COVID-19-positive mothers. The aim of this study was to use the relevant case reports and series to determine the percentage of newborns who test positive for COVID-19 who are born to COVID-19-positive mothers. Secondary outcomes included examining laboratory abnormalities among COVID-19-positive neonates, and any depicted placental abnormalities in COVID-19-positive mothers. For this purpose, systematic review was performed on all studies reporting primary data on fetus-mother pairs with COVID-19. Data bases were searched for studies that met our inclusion and exclusion criteria.


Final screening revealed 67 studies, from which the primary data of 1787 COVID-19 mothers were identified and had their pregnancy outcome analyzed. Only 2.8% of infants born to COVID-19-positive mothers tested positive, and this finding is identical to percentages reported in former Coronaviridae outbreaks, whereas 20% manifested with intrauterine hypoxia alongside placental abnormalities suggestive of heavy placental vaso-occlusive involvement.


These findings suggest that while vertical transmission is unlikely, there appears to be an underlying risk of placental insufficiency due to the prothrombotic tendency observed in COVID-19 infection. Guidelines for proper prophylactic anticoagulation in COVID-positive mothers need to be established.


COVID-19 (coronavirus disease 2019), which has been declared a pandemic in March 2020, has caused an unprecedented uncertainty within the scientific community. Contradictory scientific evidences are released almost every day, on every aspect of the pandemic from its pathogenesis, to the methods of transmission, and to the possible compassionate use of medications to combat it. Transplacental transmission of COVID-19 is one of the topics that have raised conflicting evidences across the globe. The dilemma about transplacental transmission of Coronaviridae is not exclusive to the current outbreak. To our knowledge, nine studies [1,2,3,4,5,6,7,8,9] from SARS-1 (Severe Acute Respiratory syndrome) and HKCoV (Hong Kong Coronavirus) and MERS (Middle East Respiratory syndrome) outbreaks were reported, ranging from case reports to retrospective case reviews, comprising 71 mother-infant pairs. Table 1 summarizes the findings of the nine studies. Two cases only have shown vertical transmission, a remarkable finding was the strong evidence in those reports of intrauterine fetal hypoxia possibly due to placental damage or even direct evidence of placental infarctions. Gagneur et al. [6] reported two cases of still birth that was preceded by fetal heart deceleration, whereas Wong et al. [3] and Jeong et al. [1] demonstrated placental infarction in three cases. Analysis of placental outcomes was largely lacking in the studies performed in the previous outbreaks; however, all studies that mentioned the presence of placental vascular compromise namely Wong et al. [3] and Jeong et al. [1] excluded the presence of any maternal co-morbidity that can cause such finding (Table 1). The latter finding might signify that CoV are mainly implicated in the thrombotic injury observed in such case reports. The vascular tropism of COVID-19 has recently gained so much interest, and many of its multi-organ manifestations has been attributed to its endothelial tropism. Such endothelial tropism is accounted for by the high load of Angiotensin Converting Enzyme 2 (ACE2) and Furin [10, 11], which are important viral checkpoints, in the endothelium. The placenta is a vascular organ, in which Furin plays an important role in its differentiation; moreover, ACE2 and angiotensin 1-7 are heavily expressed in it, making the placenta an important target for the vascular tropic effect of COVID-19. As mentioned earlier, the conflicting evidence regarding vertical transmission of COVID-19 and the effect of maternal COVID-19 on newborns and their placenta, render systematic review of the clustered cases available of utmost importance to build stronger evidence for the neonatal outcomes of COVID-19. The primary outcome parameter of this systematic review is the percentage of newborns testing positive to COVID-19 mothers, while secondary outcome parameters included the assessment of laboratory abnormalities among COVID-19 newborns, and the placental abnormalities encountered in COVID-19 mothers.

Table 1 Reported cases of vertical transmission, clinical manifestations and placental abnormalities in SARS-1, HKCoV, and MERS

Main text


This systematic review has been conducted in agreement with the guidelines of the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) [12].

Data search

A computer run has been performed in EMBASE, MEDLINE, and the Cochrane Central Register (From 1 November 2019 to 1 of August 2020). The following terms were included in the search: “COVID-19” OR “SARS-CoV-2” (Severe Acute Respiratory syndrome Coronaviridae 2) AND “Pregnancy” AND “Perinatal”.

Study selection criteria

Population: Pregnant women

Intervention: COVID-19

Comparison: No comparison has been a purpose of the study

Outcome: Neonatal infection by COVID-19, placental abnormalities, laboratory abnormalities in the newborn.

Observational epidemiological studies and case reports addressing the clinical conditions of mother–fetus pairs. Primary data of patients over 18 years old were considered eligible. Manuscripts that contained only data from pregnant women, or only fetuses, or that did not address the period of delivery, such as puerperium, were disregarded. All data from eligible studies were extracted by 2 independent investigators according to a standard protocol.

Statistical analysis

Each of the maternal manifestations, neonatal manifestations, placental microscopic and macroscopic changes, and laboratory changes in COVID-19-positive newborns was quantified and expressed as number (n) and percentages. Cases where evidence of placental thrombotic process have been detected and in which maternal co-morbidities were mentioned (whether ruled out or confirmed/n = 17) have been analyzed using receiver operating characteristic (ROC) analysis, and Fig. 1 is a ROC curve showing absence of possible relationship between maternal co-morbidities and placental thrombotic process with a P value of 0.6.

Fig. 1
figure 1

PRISMA flowchart for the process of study selection. Abbreviations: Preferred Reporting Items for Systematic Reviews and Meta-Analyses


The literature search identified initially 114 studies, of which 50 studies were excluded. Twenty three were excluded as they did not tackle the primary outcome parameter of the study; while 27 studies were excluded due to repetition. Total number of studies included was 64 studies, comprising 1787 Mother-infant pair [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76]. (PRISMA flow chart illustrated in Fig. 1 carries more details on the process of selecting the analyzed studies).

The studies carried out in 15 countries are listed in Table 2 alongside their main outcome parameters. The number of COVID-19-positive mothers is 1787 and the number of infants testing positive 45. There was a total of 19 fetal/neonatal deaths reported while only 72 placentae got examined.

Table 2 Summary of data in the included studies of vertical transmission of COVID-19

These data are further analyzed in Table 3 which summarizes the clinical manifestations of included COVID-19-positive mothers and the subsequent percentage of positive newborns. Out of 1787 mother-infant pairs, only 45 tested positive (2.5%), which is nearly identical to the percentage of neonates affected in the reported case series during the previous three outbreaks caused by Coronaviridae, 2/71 (2.8%) (Table 1). Among COVID-19-positive neonates, 24% were asymptomatic. The commonest array of manifestations among COVID-19-positive neonates was those suggestive of intrauterine hypoxia (20%).

Table 3 Gestational age, infection timing, and clinical characteristics of COVID-19-positive mothers and neonates

Table 4 outlines the placental abnormalities in COVID-19-positive mothers. Placental infarction, an evidence of vascular compromise of the villi, was observed in a significant number of abnormal placentae (64%). Positive swabs retrieved from abnormal placentae accounted for 27% of all abnormal placentae, and 15% of all examined placentae, a percentage lower than that of infarcted placentae. A closer percentage of placental infarctions was observed in placentae examined from the previous outbreak.

Table 4 Placental abnormalities in placentae of COVID-19 positive mothers in retrieved studies

Table 5 shows the laboratory abnormalities in COVID-19-positive neonates; the commonest laboratory abnormality in affected neonates is lymphopenia encountered in 20% of cases.

Table 5 Laboratory abnormalities in COVID-19-positive neonates

Figure 2 is a ROC curve proving the absence of relationship between maternal co-morbidities and the occurrence of placental vascular compromise of thrombotic process.

Fig. 2
figure 2

ROC curve showing the relationship between maternal co-morbidities and placental vascular compromise. Abbreviations: AUC: area under the curve, P: Pearson coefficient for statistical significance, ROC: receiver operating characteristics

Bias assessment was performed using the Cochrane revised tool for bias assessment and illustrated [77] in Fig. 3; the main defect encountered was the lack of unified outcome parameters in the collected studies. Only 18 studies explored placental abnormalities, with only 72 placentae examined in 1787 COVID-19-positive mothers.

Fig. 3
figure 3

Risk of bias assessment in the included studies


Vertical transmission of COVID-19 follows the same pattern of uncertainty as almost everything concerning COVID-19. New evidences being unraveled every day make meta-analysis the only possible solution to reach consensus about points of dilemma.

This report is by far the largest systematic review to be implemented in this context, not only regarding the number of mother-infant pairs, but also the targeted outcome parameters. The largest report preceding us is Lopes de Sousa et al.’s report [78]. Lopes de Sousa report included 755 pregnancies, while our review studied the outcome of 1787 pregnancies, also Lopes de Sousa report did not focus on placental abnormalities and its correlations with neonatal outcomes.

Our study confirmed the previous impression from the former outbreaks by CoV that transplacental transmission is very unlikely occurring in 2.8% of all positive mothers. Despite being unlikely, it has been reported to happen and this should warrant further studies on the mechanisms underlying the variability of vertical transmission from pregnancy to another.

The commonest laboratory finding in affected neonates was lymphopenia. This finding goes in agreement with the same pattern of haematologic abnormalities encountered in adult patients. The programmed cell death receptor 1 secreted from macrophages in the lung environment as well as from resident T cells leads finally to T cell exhaustion with subsequent lymphopenia in affected patients.

The most intriguing finding uncovered in our review is the strong evidence pointing towards placental damage with subsequent intrauterine hypoxia of the fetus. This finding was supported at several stages in our study. As mentioned earlier, 20% of all infants in whom manifestations have been reported have showed evidence of intrauterine hypoxia. Placental damage could not be attributed to maternal co-morbidities as proven by the ROC analysis performed which showed that maternal co-morbidities failed to predict the occurrence of placental vascular compromise with an insignificant P value of 0.6. Moreover, 7 cases were born premature in Shanes et al. series [52], all of which were demonstrating evidence of thrombosis in their respective placentae, with negative swabs for SARS-CoV-2. The timing of swab performance was not clearly mentioned in his analysis. The remaining nine neonates were born full term, 3 of them only showed placental abnormalities; among these 3 neonates, who showed placental abnormalities, two displayed evidence of intrauterine hypoxia and were small for dates. The prevalence of placental abnormalities in premature deliveries and the results of ROC analysis might not be enough to prove the role of COVID-19 in inducing placental damage, but they fortify such hypothesis. More solid findings need to be achieved through case/control studies.

A report by Wang and colleagues [79] suggested that viremia is reported to occur in less than 1% of cases. However, this finding seems to hugely underestimate the burden of viremia in Coronaviridae infections. An old report by Chen et al. [80] during the first SARS outbreak showed that RNA of SARS-CoV can be detected in up to 50% of blood samples and can last up to 1 week.

This old evidence of longstanding viremia might explain the observed placental damage, as placenta is a heavily vascularized organ; however, more studies should correlate the degree of placental damage with the duration and degree of viremia.

Placental changes were more prevalent than COVID-19-positive neonates, 62 vs. 45 respectively, out of which 64% showed evidence of ischemia. Placental changes encountered seemed to mirror the timeline at which infection was detected in COVID-19-positive mothers. Three percent of mothers were infected in the 1st trimester, while defective proliferation and formation of villi was observed in a similar percentage of cases.

Defective formation of villi can be accounted due to the role played by an intracellular enzyme termed Furin in the genesis of placental villi [81,82,83]. AbdelMassih outlined the important interplay between Furin, COVID-19, and the vascular endothelium, an important constituent of the human placenta [11].

The findings of our study also go in agreement with that of Cardenas and colleagues; Cardenas et al proved that viruses that do not exhibit vertical transmission might cause placental damage. They also proved that viral infection of the placenta can elicit a fetal inflammatory response that, in turn, can cause organ damage and potentially downstream developmental anomalies. Furthermore, we demonstrate that viral infection of the placenta may sensitize the pregnant mother to bacterial products and promote preterm labor [84].

One of the final reports included in our review concluded that vertical transmission is unlikely in COVID-19. The case/control study performed by Edlow and colleagues showed that placental malperfusion even without gross visible pathology in the placenta is not uncommon event, with resultant risk of fetal distress [73].

In view of the above findings, proper hydration and prophylactic anticoagulation might be needed for COVID-19 pregnant women, especially those whose tests suggest strong prothrombotic tendency such as elevated D-Dimer, or those whose abdominal ultrasound and fetal cardiotocography offer a strong evidence of placental insufficiency. The guidelines of several obstetrics and gynecological international societies were clustered by D’Souza et al. and were in agreement with our suggestions [85].

Fetal hypoxia can also impact neonatal outcome. Meconium staining with subsequent risk of meconium aspiration is particularly prevalent in pregnancies complicated with fetal hypoxia. Anticipation of meconium staining in pregnancies complicated by COVID-19 would be highly indicated to neonatologists in the delivery room [86]. Moreover, fetal hypoxia increases the likelihood of persistent pulmonary hypertension and failure of ductal closure after birth, this impact should be considered during postnatal assessment of neonates born to COVID-19 mothers [87].

Limitations of our study

The sampling time was not reported in 31% of cases which is a non-negligible number putting a huge risk of reporting bias. Forty two percent of positive newborns were tested in the first 12 h after delivery while the remainder 58% of cases were tested after 12 h, raising suspicion of possible postnatal infection.

The lack of homogenous outcome parameter illustrated in Fig. 3 can lead to an underestimation of placental abnormalities; however, the high percentage of placental abnormalities out of the few examined placentae partially resolves this issue. Another limitation of the studies is the relative weight of case reports compared to case series and retrospective studies. Two studies by Kayem et al. [55] and Knight Dphil et al. [53] constitute 58% of all counted in pregnancy outcomes. The limitation of sample size was clearly and extensively discussed by Lopes de Sousa et al. [78].


The aggregated data in this systematic review are by far the largest to date regarding neonatal outcomes of COVID-19. Results suggest that vertical transmission of COVID-19 is unlikely as it occurred in 2.8% of neonates but underlines an important and underestimated risk, which is the possible placental insufficiency due to the prothrombotic tendency created by COVID-19. These findings should warrant more case/control studies to compare placental abnormalities with the duration and degree of viremia. Also thorough antenatal care should be offered to COVID-19-positive mothers to evaluate their prothrombotic tendency and to monitor their need for anticoagulation. Finally, yet importantly, complications such as meconium aspiration and PPHN should be compared in COVID-19-positive vs. COVID-19-negative mothers and should be anticipated by neonatologists in the delivery room and during follow-up after delivery.

Availability of data and materials

Not applicable.



Angiotensin converting enzyme 2


Central nervous system


Coronavirus disease 19


Gestational age


Gastro-esophageal reflux disease


Gastro-intestinal system


Hong Kong Coronavirus


Intrauterine growth retardation


Middle East Respiratory Syndrome

N :



Necrotizing enterocolitis


Obstetrics and gynecology


Preferred Reporting Items for Systematic Reviews and Meta-Analysis


Respiratory distress syndrome


Severe acute respiratory syndrome


  1. Jeong SY et al (2017) MERS-CoV infection in a pregnant woman in Korea. J. Korean Med. Sci. 32:1717–1720

    Article  Google Scholar 

  2. Payne DC et al (2014) Stillbirth during infection with Middle East Respiratory Syndrome Coronavirus. J. Infect. Dis. 209:1870–1872

    Article  Google Scholar 

  3. Wong SF et al (2004) Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am. J. Obstet. Gynecol. 191:292–297

    Article  Google Scholar 

  4. Yudin MH et al (2005) Severe acute respiratory syndrome in pregnancy. Obstet. Gynecol. 105:124–127

    Article  Google Scholar 

  5. Stockman LJ, Lowther SA, Coy K, Saw J, Parashar UD (2004) SARS during pregnancy, United States [2]. Emerg Infect Dis.

  6. Gagneur A et al (2008) Materno-fetal transmission of human coronaviruses: a prospective pilot study. Eur. J. Clin. Microbiol. Infect. Dis. 27:863–866

    Article  CAS  Google Scholar 

  7. Li AM (2005) Severe acute respiratory syndrome (SARS) in neonates and children. Arch. Dis. Child. - Fetal Neonatal Ed. 90:F461–F465

    Article  CAS  Google Scholar 

  8. Shek CC, Ng PC, Fung GP, Cheng FW, Chan PK, Peiris MJ, Lee KH, Wong SF, Cheung HM, Li AM, Hon EK, Yeung CK, Chow CB, Tam JS, Chiu MC,  Fok TF. (2003) Infants born to mothers with severe acute respiratory syndrome. Pediatrics. 112(4):e254.

  9. Robertson CA et al (2004) SARS and pregnancy: a case report. Emerg. Infect. Dis. 10:345–348

    Article  Google Scholar 

  10. Li M, Chen L, Zhang J, Xiong C, Li X. (2020) The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLoS One. 15(4):e0230295. Published 2020 Apr 16.

  11. AbdelMassih AF et al (2020) A multicenter consensus: a role of furin in the endothelial tropism in obese patients with COVID-19 infection. Obesity Med.

  12. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J. Clin. Epidemiol.

  13. Khan S et al (2020) Association of COVID-19 with pregnancy outcomes in health-care workers and general women. Clin Microbiol Infect.

  14. Hantoushzadeh S et al (2020) Maternal death due to COVID-19. Am. J. Obstet. Gynecol.

  15. Chen S et al (2020) Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia. J. Med. Virol.

  16. Chen R et al (2020) Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients. Can. J. Anesth.

  17. Ferrazzi E et al (2020) Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis. BJOG An Int. J. Obstet. Gynaecol.

  18. Dashraath P et al (2020) Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am. J. Obstet. Gynecol.

  19. Baud D et al (2020) Second-trimester miscarriage in a pregnant woman with SARS-CoV-2 infection. JAMA.

  20. Dong L et al (2020) Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA.

  21. González Romero D, Ocampo Pérez J, González Bautista L, Santana-Cabrera L (2020) Pregnancy and perinatal outcome of a woman with COVID-19 infection. Revista Clinica Espanola.

  22. Breslin N et al (2020) Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant women: two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am. J. Obstet. Gynecol. MFM.

  23. Alzamora MC et al (2020) Severe COVID-19 during pregnancy and possible vertical transmission. Am. J. Perinatol.

  24. Chen H et al (2020) Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet.

  25. Qiancheng X et al (2020) Coronavirus disease 2019 in pregnancy. Int. J. Infect. Dis.

  26. Liu Y, Chen H, Tang K, Guo Y (2020) Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy. J Infect.

  27. Liao X, Yang H, Kong J, Yang H (2020) Chest CT findings in a pregnant patient with 2019 novel coronavirus disease. Balkan Med. J.

  28. Yu N et al (2020) Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect. Dis.

  29. Kirtsman M et al (2020) Probable congenital sars-cov-2 infection in a neonate born to a woman with active sars-cov-2 infection. CMAJ.

  30. Kang X, Zhang R, He H, Yao Y, Zheng Y, Wen X, Zhu S. (2020) [Anesthesia management in cesarean section for a patient with coronavirus disease 2019]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 49(1):249-252. Chinese.

  31. Buonsenso D et al (2020) Clinical role of lung ultrasound for diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet. Gynecol.

  32. Lu D et al (2020) Asymptomatic COVID-19 infection in late pregnancy indicated no vertical transmission. J. Med. Virol.

  33. Khan S et al (2020) Impact of COVID-19 infection on pregnancy outcomes and the risk of maternal-to-neonatal intrapartum transmission of COVID-19 during natural birth. Infect Control Hosp Epidemiol.

  34. Kalafat E et al (2020) Lung ultrasound and computed tomographic findings in pregnant woman with COVID-19. Ultrasound Obstet. Gynecol.

  35. Karami P et al (2020) Mortality of a pregnant patient diagnosed with COVID-19: a case report with clinical, radiological, and histopathological findings. Travel Med. Infect. Dis.

  36. Nie R et al (2020) Clinical features and the maternal and neonatal outcomes of pregnant women with coronavirus disease 2019.

    Book  Google Scholar 

  37. Lowe B, Bopp B (2020) COVID-19 vaginal delivery – a case report. Aust. New Zeal. J. Obstet. Gynaecol.

  38. Chen S et al (2020) Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases. Zhonghua Bing Li Xue Za Zhi.

  39. Li Y et al (2020) Lack of vertical transmission of severe acute respiratory syndrome Coronavirus 2, China. Emerg. Infect. Dis 26:1335–1336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fan C et al (2020) Perinatal transmission of COVID-19 associated SARS-CoV-2: should we worry? Clin. Infect. Dis.

  41. Zambrano LI et al (2020) A pregnant woman with COVID-19 in Central America. Travel Med Infect Dis.

  42. Iqbal SN et al (2020) An uncomplicated delivery in a patient with Covid-19 in the United States. New Engl J Med.

  43. Wang X et al (2020) A case of 2019 novel coronavirus in a pregnant woman with preterm delivery. Clin. Infect. Dis. 71:844–846

    Article  CAS  Google Scholar 

  44. Xiong X et al (2020) Vaginal delivery report of a healthy neonate born to a convalescent mother with COVID­-19. J. Med. Virol:jmv.25857.

  45. Lee DH et al (2020) Emergency cesarean section performed in a patient with confirmed severe acute respiratory syndrome Coronavirus-2 -a case report. Korean J. Anesthesiol. 73:347–351

    Article  CAS  Google Scholar 

  46. Yue L et al (2020) Anaesthesia and infection control in cesarean section of pregnant women with coronavirus disease 2019 (COVID-19):1–17.

  47. Liu W et al (2020) Clinical characteristics of 19 neonates born to mothers with COVID-19. Front. Med.

  48. Shi H et al (2020) Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect. Dis.

  49. Liao J et al (2020) Analysis of vaginal delivery outcomes among pregnant women in Wuhan, China during the COVID-19 pandemic. Int. J. Gynecol. Obstet.

  50. Yin M, Zhang L, Deng G, et al. (2020) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy In China: A Retrospective Cohort Study. medRxiv;

  51. Li N et al (2020) Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study. Clin. Infect. Dis.

  52. Shanes ED et al (2020) Placental Pathology in COVID-19. Am. J. Clin. Pathol.

  53. Knight Dphil M et al (2020) Characteristics and outcomes of pregnant women hospitalised with confirmed SARS-CoV-2 infection in the UK: a national cohort study using the UK Obstetric Surveillance System (UKOSS) The UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Co. medRxiv 2020.05.08.20089268.

  54. Govind A et al (2020) Re: novel coronavirus COVID-19 in late pregnancy: Outcomes of first nine cases in an inner city London hospital. Eur J Obstetrics Gynecol Reprod Biol.

  55. Kayem G et al (2020) A snapshot of the Covid-19 pandemic among pregnant women in France. J. Gynecol. Obstet. Hum. Reprod:101826.

  56. Nyholm S et al (2020) Invasive mechanical ventilation in a former preterm infant with COVID-19. Acta Paediatr:apa.15437.

  57. Easterlin MC, De Beritto T, Yeh AM, Wertheimer FB, Ramanathan R (2020) Extremely preterm infant born to a mother with severe COVID-19 pneumonia. J. Investig. Med. High Impact Case Reports 8:232470962094662

    Article  Google Scholar 

  58. Wu Y et al (2020) Coronavirus disease 2019 among pregnant Chinese women: case series data on the safety of vaginal birth and breastfeeding. BJOG An Int. J. Obstet. Gynaecol.

  59. Hong L et al (2020) Severe COVID-19 infection in pregnancy requiring intubation without preterm delivery: A case report. Case Rep Womens Heal. 27:e00217

    Article  Google Scholar 

  60. Vivanti AJ et al (2020) Transplacental transmission of SARS-CoV-2 infection. Nat. Commun. 11:3572

    Article  CAS  Google Scholar 

  61. Salvatori G et al (2020) Managing COVID-19-positive maternal-infant dyads: an italian experience. Breastfeed. Med. 15:347–348

    Article  Google Scholar 

  62. Wu Y-T et al (2020) Neonatal outcome in 29 pregnant women with COVID-19: A retrospective study in Wuhan, China. PLOS Med 17:e1003195

    Article  CAS  Google Scholar 

  63. Sisman J et al (2020) Intrauterine transmission of SARS-COV-2 infection in a preterm infant. Pediatr. Infect. Dis. J 39:e265–e267

    Article  Google Scholar 

  64. Yang P et al (2020) Clinical characteristics and risk assessment of newborns born to mothers with COVID-19. J. Clin. Virol. 127:104356

    Article  CAS  Google Scholar 

  65. Zheng T et al (2020) Coronavirus disease 2019 (COVID-19) in pregnancy: 2 case reports on maternal and neonatal outcomes in Yichang city, Hubei Province, China. Medicine (Baltimore) 99:e21334

    Article  CAS  Google Scholar 

  66. Wang S et al (2020) A case report of neonatal 2019 coronavirus disease in China. Clin. Infect. Dis. 71:853–857

    Article  CAS  Google Scholar 

  67. Dumpa V, Kamity R, Vinci AN, Noyola E, Noor A (2020) Neonatal coronavirus 2019 (COVID-19) infection: a case report and review of literature. Cureus.

  68. Masmejan S et al (2020) Vertical transmission and materno-fetal outcomes in 13 patients with coronavirus disease 2019. Clin. Microbiol. Infect.

  69. Yang H, Hu B, Zhan S, Yang L, Xiong G (2020) Effects of SARS-CoV-2 infection on pregnant women and their infants: a retrospective study in Wuhan, China. Arch. Pathol. Lab. Med.

  70. Hillary H et al (2020) First case of placental infection with SARS-CoV-2. medRxiv

  71. Ferraiolo A et al (2020) Report of positive placental swabs for SARS-CoV-2 in an asymptomatic pregnant woman with COVID-19. Medicina (B. Aires). 56:306

    Article  Google Scholar 

  72. Ng WF et al (2006) The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation. Pathology 38:210–218

    Article  CAS  Google Scholar 

  73. Edlow AG et al (2020) Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw. Open 3:e2030455

  74. Zeng H et al (2020) Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA.

  75. Liu D et al (2020) Pregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: a preliminary analysis. AJR. Am. J. Roentgenol.

  76. Zhu H et al (2020) Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl. Pediatr.

  77. Sterne JAC et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ:l4898.

  78. Lopes de Sousa ÁF et al (2020) Effects of COVID-19 infection during pregnancy and neonatal prognosis: what is the evidence? Int. J. Environ. Res. Public Health 17:4176

    Article  Google Scholar 

  79. Wang W et al (2020) Detection of SARS-CoV-2 in different types of clinical specimens. JAMA.

  80. Chen W et al (2004) Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)-associated coronavirus infection. J. Med. Microbiol. 53:435–438

    Article  CAS  Google Scholar 

  81. Chin AM, Hill DR, Aurora M, Spence JR (2017) Morphogenesis and maturation of the embryonic and postnatal intestine. Semin. Cell Dev. Biol. 66:81–93

    Article  Google Scholar 

  82. Zhou Z et al (2013) The proprotein convertase furin is required for trophoblast syncytialization. Cell Death Dis. 4:1–10

    Google Scholar 

  83. Zhou Z et al (2013) The proprotein convertase furin is required for trophoblast syncytialization. Cell Death Dis. 4

    Google Scholar 

  84. Cardenas I et al (2010) Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J. Immunol. 185:1248–1257

    Article  CAS  Google Scholar 

  85. D’Souza R et al (2020) A critical review of the pathophysiology of thrombotic complications and clinical practice recommendations for thromboprophylaxis in pregnant patients with COVID-19. Acta Obstet. Gynecol. Scand:1–11.

  86. Westgate JA, Bennet L, Gunn AJ (2002) Meconium and fetal hypoxia: some experimental observations and clinical relevance. BJOG An Int. J. Obstet. Gynaecol. 109:1171–1174

    Article  Google Scholar 

  87. Delaney C, Cornfield DN (2012) Risk factors for persistent pulmonary hypertension of the newborn. Pulm. Circ. 2:15–20

    Article  CAS  Google Scholar 

Download references


To our families who are bearing the weight of our sacrifice of time to our patients. If our families were not understanding to the depth of our struggle, we would have never been able to keep the same level of dedication to our patients. To our students that we involve in each step of our researches to make them flourish in this field and take the lead the soonest the possible.


This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations



AA, LE, MA, and MT contributed to the conception and design of the work. RF, RE, DH, DK, YO, SAb, MaI, and MoI contribute significantly to the acquisition of data. HA, HI, AN, GA, IG, LM, MS, MH, ME, NE, NA, NS, RD, RS, RR, SAl, SI, SAh, SK, and SP contributed to the analysis and interpretation of data. R.M contributed to the drafting and revision of the manuscript. All authors have approved the submitted version. All authors have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

Corresponding author

Correspondence to Antoine AbdelMassih.

Ethics declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

AbdelMassih, A., Fouda, R., Essam, R. et al. COVID-19 during pregnancy should we really worry from vertical transmission or rather from fetal hypoxia and placental insufficiency? A systematic review. Egypt Pediatric Association Gaz 69, 12 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: