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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 6  |  Issue : 4  |  Page : 287-293

Pregnancy during COVID-19 pandemic – Maternal and neonatal outcomes: A concise review


1 Internal Medicine, Islamic International Medical College, Riphah International University, Rawalpindi, Pakistan
2 Internal Medicine, Jawaharlal Nehru Medical College, Aligarh, Uttar Pradesh, India; Kingsbrook Jewish Medical Center, Brooklyn, NY, USA
3 Internal Medicine, Maharashtra Institute of Medical Education and Research, Pune, Maharashtra, India
4 Department of Anesthesiology and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA

Date of Submission12-Jul-2020
Date of Acceptance05-Oct-2020
Date of Web Publication24-Dec-2020

Correspondence Address:
Dr. Rahul Kashyap
Department of Anesthesiology and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAM.IJAM_94_20

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  Abstract 


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began as an epidemic in China and has spread rapidly in many other countries. Severe adverse pregnancy outcomes resulted from SARS and Middle-East respiratory syndrome. Although consequences of infection with SARS-COV-2 for pregnancies are uncertain at this time, the possibility of severe outcomes should be considered. The physiological maternal adaptations in pregnancy predisposed women to more severe pneumonia, resulting in higher maternal morbidity. There is a paucity of literature regarding the effect of SARS-CoV-2 infection during pregnancy, thus limiting both counseling and management of these patients. This literature review combines the studies from different geographical locations and focuses on whether SARS-CoV-2 infection is transmitted vertically from mothers to neonates and if there are adverse pregnancy and neonatal outcomes such as fetal distress, premature labor, and acute respiratory distress syndrome. We also reviewed the guidelines regarding breastfeeding during the SARS-CoV-2 pandemic. We have used PubMed utilizing search terms as COVID-19, pregnancy, SARS-CoV-2, coronavirus, and pregnancy outcomes. We found sixty studies that met our inclusion criteria, of which total ten studies were included in the review. Inclusion criteria are based on the studies which had pregnant women who were exposed to SARS-CoV-2 and had information on vertical transmission of SARS-CoV-2. Currently, there is no evidence that SARS-CoV-2 undergoes intrauterine or transplacental transmission from infected pregnant women to their fetuses. Based on the current course of SARS-CoV-2 and its rampant growth, it is reasonable to expect that an enormous number of possible asymptomatic pregnant women will present for care. It is suggested that SARS-CoV-2 infection is commonly asymptomatic and should be suspected in all pregnant patients in areas with predominant disease.
The following core competencies are addressed in this article: Medical knowledge, Patient care, Systems-based practice.

Keywords: Coronavirus, COVID-19, pregnancy outcomes, pregnancy, severe acute respiratory syndrome coronavirus 2


How to cite this article:
Khan H, Sabzposh H, Deshpande S, Kashyap R. Pregnancy during COVID-19 pandemic – Maternal and neonatal outcomes: A concise review. Int J Acad Med 2020;6:287-93

How to cite this URL:
Khan H, Sabzposh H, Deshpande S, Kashyap R. Pregnancy during COVID-19 pandemic – Maternal and neonatal outcomes: A concise review. Int J Acad Med [serial online] 2020 [cited 2021 Apr 12];6:287-93. Available from: https://www.ijam-web.org/text.asp?2020/6/4/287/304607




  Introduction Top


The novel coronavirus was first detected in Wuhan City, the capital of Hubei Province. During the 1st weeks of January 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus spread rapidly to other countries including Thailand, Japan, Korea, the United States, and Iran.[1] The overall mortality rate ranges from 3% to 4%, according to the World Health Organization reports. As of August 15, 2020, there are more than 21 million cases of coronavirus and >767,000 deaths confirmed globally.[2]

The most common manifestations of SARS-CoV-2 infection are fever, cough, fatigue, myalgia, sputum production, and headache. The existing literature has shown statistics of fever 48%, cough 65%, myalgias/fatigue 38%, dyspnea 24%, chest pain 17%, and headache 28%. There are scarce data on adverse pregnancy outcomes in pregnant women infected with SARS-CoV-2 as the appearance of coronavirus was not seen formerly in humans.[3]

There is limited published literature related to vertical transmission, and more studies need to be conducted. It is important to know about vertical transmission and complications in pregnant women related to SARS-CoV-2 infection such as miscarriage, preterm birth, preeclampsia, preterm premature rupture of membranes (PROM), and fetal growth restriction. One of the main concerns related to SARS-CoV-2 infection is the development of an acute respiratory distress syndrome, which often requires invasive ventilation.[4]


  Methods Top


A search was conducted on PubMed and Google Scholar with search terms for COVID-19, pregnancy, SARS-CoV-2, coronavirus, pregnancy outcomes, and vertical transmission. Ten studies are included in this review [Figure 1]. Studies without these keywords were excluded from this review.
Figure 1: Consort diagram of included studies

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One meta-analysis study, which consisted of 19 studies included 79 hospitalized women reported that 41 pregnancies (51.9%) were affected by SARS-CoV-2. An apparent diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (83%), cough (57%), and dyspnea (27%).[3] Pregnant patients who are infected with SARS-CoV-2, the most common adverse pregnancy outcome is preterm birth. SARS-CoV-2 infection is associated with a relatively higher rate of preeclampsia, cesarean, and perinatal death [Figure 2].
Figure 2: Maternal and fetal outcomes in pregnancies affected by COVID-19, Middle-East respiratory syndrome, and severe acute respiratory syndrome

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Viral pneumonia is an important cause of mortality among pregnant women. Pneumonia causes several adverse obstetrical outcomes including PROM and preterm labor (PTL), intrauterine fetal demise, intrauterine growth restriction, and neonatal death.[3]

Statistics from earlier coronaviruses (SARS-CoV and Middle-East respiratory syndrome [MERS]-CoV) studies proposed that pregnant women may be at higher risk of severe illness and mortality than the general population.[5] Pregnant women are more susceptible to infections as there is increased oxygen consumption and decreased functional residual capacity of lungs during pregnancy. SARS-CoV-2 may impose a greater risk in pregnant women compared to the nonpregnant adult population [Figure 3]. At present, little information is known about SARS-CoV-2, especially related to its effect on pregnant women and neonates, and currently, there are no recommendations pertinent to pregnant women regarding the evaluation or management of SARS-CoV-2. At this time, it is not known whether SARS-CoV-2 virus can be transmitted through breast milk, but it is established that an infected mother can transmit the virus through respiratory droplets during breastfeeding.[3]
Figure 3: Percent of COVID-19-positive hospital admissions by status and weeks in March Tekbali et al.; pregnant versus nonpregnant severe acute respiratory syndrome coronavirus 2 and COVID-19 hospital admissions: The first 4 weeks in New York, Am J Obstet Gynecol (2020)

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Neonatologists should evaluate neonates who are born to mothers suspected or confirmed with SARS-CoV-2 infection. It is recommended that neonates born to mothers with prenatal and postnatal fever or PROM or if neonate has premature birth, low birth weight, is small for gestational age, the neonate should be admitted into the neonatal isolation ward as soon as possible. In the ward, any change in condition is closely monitored, and symptomatic and supportive treatments should be administered timely. Interventions may be initiated depending on the chest radiographic findings, nucleic acid test (NAT) results, and the patient's symptoms and signs. It is recommended to use intravenous gamma globulin for passive immunization early.[6]


  Maternal Outcomes Related to Severe Acute Respiratory Syndrome Coronavirus 2 Top


SARS-CoV-2 is categorized in the group of betacoronavirus subtype similar to coronavirus, which is responsible for SARS and MERS. Yu et al. examined seven patients in the age range of 29–34 years and mean gestational age of 37–41 weeks. Two patients had a history of chronic condition (hypothyroidism and polycystic ovary syndrome) and three patients had uterine scarring. All the patients had a contact history of the epidemic area [Table 1]. On admission, six patients had fever, one had cough, one had shortness of breath, and one had diarrhea. Two patients also had H1N1 and one had Legionella pneumophila coinfection. Computed tomography (CT) chest findings were positive for six patients which showed bilateral pneumonia and one patient had unilateral pneumonia. In terms of treatment, all of the patients received oxygen therapy and antiviral therapy which included oseltamivir, ganciclovir, and interferon inhalation. Two patients were given single antibiotic therapy, and five of them were given combination antibiotics. Antibiotics were cephalosporins, quinolones, and macrolides. Five patients were given methylprednisolone. Cesarean section was performed on all the patients. After all these interventions, it was seen that maternal outcomes were good. There were no intensive care unit (ICU) admissions for the mothers before and after delivery, and all of them were discharged after their body temperature returned to normal, respiratory symptoms improved, and pulmonary image showed improvement. The NAT of respiratory secretions was negative twice in row. Form the above study, it was inferred that, for a full-term pregnant woman, there should be a consultation with a multidisciplinary team. The delivery should be as soon as possible and timely use of antibiotics to reduce secondary infections and to boost immune support can reduce complications and mortality.[5]
Table 1: Summary of pregnancy-related outcomes in COVID-19

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In another meta-analysis of the outcomes of coronavirus spectrum infection, Daniel Di Mascio et al compared the effects of SARS, MERS and COVID-19 during pregnancy, maternal outcomes and neonatal outcomes [Table 2].[4]
Table 2: Comparative (severe acute respiratory syndrome – Middle-East respiratory syndrome – COVID-19) display of pooled proportions of pregnancy outcomes

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The pregnancy/maternal outcomes that were observed were:

  • Preterm birth (either before 34 weeks or 37 weeks)
  • Preeclampsia
  • Preterm prelabor rupture of membrane
  • Fetal growth restriction
  • Miscarriages
  • Cesarean delivery.


Another study was conducted by Zhu et al. on the clinical analysis of ten neonates (including twins) born to nine mothers with SARS-CoV-2 pneumonia. Most of the mothers experienced fever and cough and one experienced diarrhea. Symptoms occurred before delivery in four cases, and three were treated with oseltamivir. Two cases experienced symptoms on the day of the delivery and were treated with oral oseltamivir and nebulized inhaled interferon. In the remaining three cases, symptoms occurred after delivery. The chest CT of pregnant women revealed bilateral GGO, patchy consolidation, and blurred borders. The pulmonary findings improved significantly after the treatment was given. After being infected with SARS-CoV-2, the first symptom women developed were fever and cough, which suggested that the virus infected the lower respiratory tract. One woman also developed diarrhea, suggesting that the virus can also attack the gastrointestinal tract system. However, the virus was not detected in gastric juices and feces and could not identify if the virus affects the digestive tract and requires more studies to be done.[6]


  Neonatal Outcomes Related to Severe Acute Respiratory Syndrome Coronavirus 2 Top


Yu et al. additionally reported that the neonatal birth weight and Apgar scores of all the seven infants were normal. One neonate was tested positive for SARS-CoV-2, 36 h after the birth. The neonate was transferred to children's hospital in Wuhan, a designated unit for children infected with SARS-CoV-2. The neonate was discharged after 2 weeks after two consecutive negative NATs. None of the other neonates tested positive or had any neonatal complications. Previous studies have shown no evidence of perinatal SARS infection in infants born to mothers who had SARS during pregnancy. One neonate tested positive after 36 h of birth. However, the viral NAT of the placenta and cord blood tested negative for SARS-CoV-2 negating that intrauterine transmission can occur.[5]

According to the meta-analysis of the coronavirus spectrum infection, the neonatal outcomes were as follows [Table 3]:
Table 3: Comparative (severe acute respiratory syndrome – Middle-East respiratory syndrome – COVID-19) display of pooled proportions of perinatal outcomes

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  • Fetal distress
  • APGAR score of <7 in 5 min
  • Neonatal asphyxia
  • Admission to the neonatal intensive care unit
  • Perinatal death including stillbirth and neonatal death.[4]


Zhu et al. examined the neonatal outcomes born to mothers with confirmed SARS-CoV-2 infection. Among the newborns, eight were males and two were females. Four were born full term and six were born premature infants. There were eight singletons and two twins. Six neonates had pediatric critical illness score <90. They had shortness of breath, fever, rapid heart rate, and vomiting. Seven had chest radiograph abnormalities consistent with neonatal respiratory distress syndrome and pneumothorax.[6]

All of them received supportive treatment. One patient developed refractory shock, Multiple Organ Dysfunction Syndrome (MODS) and Disseminated Intravascular Coagulation (DIC). He was treated with platelet transfusion, red blood cell, and plasma but died on 9th day. Later, five neonates were discharged from the hospital, one died and 4 remained in stable condition.[6]

Regarding the vertical transmission of SARS-CoV-2, Zhu et al. examined negative results in nine out of ten neonates and thus no evidence of vertical transmission. However, the limitation of the study was a small sample size and chances of false-negative results. More specimens such as the umbilical cord bleed, amniotic fluid and placental samples from mother, serum gastric juices, anal swabs and stools from neonates can be collected to increase the detection rate by NAT.[6]


  Transmission Through Breastfeeding Top


In one of the studies published by Yang et al., they examined that virus was not detected in the breast milk or colostrum, but the virus could be transmitted through close contact. All the newborns in China were separated from infected mothers for 14 days making direct breastfeeding impossible. However, the mothers were advised to express breast milk to maintain supply. Once they test negative for SARS-CoV-2, they could breastfeed the infant.[7] As per the Centers for Disease Control and Prevention guidelines, the separation of mother from infant is done on a case-by-case basis. In the case of a temporary separation, mothers should express breast milk using a dedicated pump which should be thoroughly washed, disinfected, and dried. Mothers who choose to breastfeed, should practice hand hygiene, and put face mask before the feed. The mask should remain in place during the feed. If another healthy family or staff member is present to provide care such as diapering, bathing, and feeding for the newborn, they should use appropriate personal protective equipment. These include gown, gloves, face mask, and eye protection.


  Prevalence and Presentation Among Different Cohorts Top


The SARS-CoV-2 pandemic continues to affect patients across the world. It is necessary to note the prevalence of maternal-to-fetal transmission of the disease and the complications that can occur in the neonate and the pregnant women.

Looking at the demographics of patients in New York as reported by Breslin et al. shows the pregnant women that present with SARS-CoV-2 symptoms had a mean age of 29.7 with a standard deviation of 6. Among the patients, 44.2% seem to have at least one comorbidity, and mild asthma seems to be the most common comorbidity among this group. Average body mass index of this group of patients was 30.9 (5.3) kg/m2.[8]

Regarding the presentation of patients, 67.4% of women reported symptoms of COVID-19. Of these patients, 69% of patients reported symptoms of SARS-CoV-2 as the chief complaint and 34.4% reported being exposed to a sick contact. As high as 31% presented only due to obstetrical reasons and were later found to be positive for the virus on screening. This shows the importance of routine screening of patients when they are admitted to the hospital as these might be the potential points of infection to other patients and the medical staff in the hospital. Early detection of these cases would help to implement timely infection control measures to control the disease.[8]

The three most common presenting symptoms were fever, cough, and myalgias. Out of these, 44.4% of patients underwent a cesarean delivery for obstetrical causes and 55.5% had vaginal deliveries. Among these pregnant women, 86% had mild disease, 9.3% severe disease, and 4.7% were critical. This presentation and severity appeared to be similar to what has been in the nonpregnant population affected by COVID-19 [Figure 4].[8]
Figure 4: Comorbidity and its impact on 1590 patients with COVID-19 in China: A nationwide analysis

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In the study by Yu N et al., of the pregnant patients with COVID-19 outside of Wuhan, China reported birth through the cesarean section in 77% (10 out of 13) of patients. They also reported that 46% (6 out of 13) had PTL between 32 and 36 weeks. Nearly 7.6% (1 out of 13) of patients developed severe pneumonia and multiorgan dysfunction requiring ICU admission.[4] This rate of severity of patients seems to be comparable to the rate seen in other studies in the general population. Another study by Yu et al. among SARS-CoV-2-positive pregnant women in Wuhan, China, studied seven patients and reported delivery through the cesarean section in all of the seven patients.[5]

Consistent finding that is being reported by Breslin et al. and Zhu et al. showed no evidence of vertical transmission of SARS-CoV-2, with none of the neonates born to the pregnant women with COVID-19 testing positive for the virus with a reverse transcription-polymerase chain reaction.[6],[8]

Thus, the presentations of the patients reported in various studies appeared to be similar, with the most common symptoms being fever, cough, and myalgias. The severity of the disease and the proportion of patients requiring critical care among the pregnant women also appeared to be similar. In spite of this, the rate of cesarean section seemed to be much higher among patients in China than that observed in the US.[5],[6],[8],[9] We need larger multicenter observational studies to find further correlation between SARS-CoV-2 and pregnancy complications.[10]

Similar to SARS, there is a theoretical risk of vertical transmission as the ACE2 receptor is widely expressed in the placenta with a similar receptor-binding domain structure between SARS-CoV and SARS-CoV-2.[11]

Because of altered physiology, increased susceptibility to infections, and compromised mechanical and immunological functions, pregnant women are a vulnerable group to any infectious disease outbreak. The need to safeguard the fetus adds to the challenge of managing their health. As clinical data are being collected on the use of antiviral therapy and corticosteroid use in pregnancy management, much of the obstetric management is based on consensus and best practice recommendations. This concise review represents an integrated framework to provide an appropriate level of care for patients and explains the maternal and perinatal outcomes of SARS-CoV-2 infection.[11]


  Conclusion Top


In a concise review of maternal and neonatal outcomes during SARS-CoV-2 pandemic, we conclude that there is no clear evidence regarding the vertical transmission of SARS-CoV-2 infection, especially when it occurs later in pregnancy. The lack of data during first- and early second-trimester infection impairs the understanding of its impact on perinatal outcomes. Studies on long-term outcomes are required with few reported cases of potential mother-to-child vertical transmission. The neonate should be separated from mother with severe SARS-CoV-2 symptoms and fed fresh expressed breast milk. There is no suggestion of transmission through human milk yet.

The main focus of this study was to investigate the possibility of intrauterine transmission of SARS-CoV-2 infection. The observation of no fetal infection caused by intrauterine vertical transmission can be affected by the small sample size and the stage of pregnancy at the onset of SARS-CoV-2 infection. The effect of SARS-CoV-2 infection on the fetus in the first or second trimester of pregnancy needs to be analyzed. Second, it needs to be further investigated that vaginal delivery increases the risk of mother-to-child intrapartum transmission and if uterine contraction can increase the possibility of the virus transmission. Third, the effects of the time or mode of delivery on pregnancy outcomes were not evaluated. Fourth, we have to see if SARS-CoV-2 affects the placenta, which represents an important link in vertical transmission, also needs to be further evaluated.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Research quality and ethics statement

The authors of this manuscript declare that this scientific work complies with reporting quality, formatting, and reproducible guidelines set forth by the EQUATOR Network. The authors also attest that this clinical investigation was determined to be exempt by our institutional IRB / Ethics Committee.



 
  References Top

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Shah A, Kashyap R, Tosh P, Sampathkumar P, O'Horo JC. Guide to understanding the 2019 novel coronavirus. Mayo Clin Proc 2020;95:646-52.  Back to cited text no. 1
    
2.
Center, J.H.C.R. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE); 2020. Available from: https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. [Last accessed on 2020 Jun 22].  Back to cited text no. 2
    
3.
Karimi-Zarchi M, Neamatzadeh H, Dastgheib SA, Abbasi H, Mirjalili SR, Behforouz A, et al. Vertical transmission of coronavirus disease 19 (COVID-19) from infected pregnant mothers to neonates: A review. Fetal Pediatr Pathol 2020;39:246-50.  Back to cited text no. 3
    
4.
Di Mascio D, Khalil A, Saccone G, Rizzo G, Buca D, Liberati M, et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: A systematic review and meta-analysis. Am J Obstet Gynecol MFM 2020;2:100107.  Back to cited text no. 4
    
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Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al. 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 2020;20:559-64.  Back to cited text no. 5
    
6.
Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr 2020;9:51-60.  Back to cited text no. 6
    
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Yang H, Wang C, Poon LC. Novel coronavirus infection and pregnancy. Ultrasound Obstet Gynecol 2020;55:435-7.  Back to cited text no. 7
    
8.
Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R, Martinez R, Bernstein K, et al. 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 2020;2:100118.  Back to cited text no. 8
    
9.
Schwartz DA. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: Maternal coronavirus infections and pregnancy Outcomes. Arch Pathol Lab Med 2020: Volume 144, Issue 7  Back to cited text no. 9
    
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Walkey AJ, Kumar VK, Harhay MO, Bolesta S, Bansal V, Gajic O, et al. The viral infection and respiratory illness universal study (VIRUS): An international registry of coronavirus 2019-related critical illness. Crit Care Explor 2020;2:e0113.  Back to cited text no. 10
    
11.
Dashraath P, Wong JL, Lim MX, Lim' LM, Li S, Biswas A, et al. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am J Obstet Gynecol 2020;222:521-31.  Back to cited text no. 11
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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