Pregnancy is a special phase in a woman’s life, more so because of the various changes which her body undergoes during these 9 months. Perhaps that is why, the concern about the threat of the novel coronavirus is valid- after all pregnancy is a state of slight immunocompromise, and also because there are two lives at stake. WHO declared the COVID-19 outbreak a pandemic on March 11, 2020. Most countries have taken stringent measures to control the spread of this disease, but do pregnant women need to take more measures? So, avid obstetricians out there, let’s find out deeply about the connection between these two:
WHO’s official stand is that there is no higher risk in pregnancy of severe illness BUT because there are trials underway and due to the bodily changes in pregnancy, one can not know the extent of COVID-19 in these patients. [1] Due to the evolving crisis, we are seeing newer studies every day with new results. A study conducted in early February on 38 pregnant women showed that it did not lead to maternal deaths, and neither were there any confirmed cases of intrauterine transmissions, with rt-PCR being negative in all the neonatal specimens tested, hence leading to the belief that there is no intrauterine or transplacental transmission. [2] Even the CT scans done on pregnant women with COVID-19 positive samples, did not show major changes and recovered from pneumonia adequately. [3]
As the epidemic spread far and wide, in more countries, affecting a more diverse population, well into March, with it finally being declared a pandemic by WHO, studies started showing a change in trends. A mother in Wuhan, a 29-year-old primiparous female at 34 weeks of gestation, was detected to be COVID-19 positive after she was detected with symptoms, ground-glass opacities in her chest CT scan as well as a positive rt-PCR nasal swab. She gave birth to an infant girl by cesarean section in a negative pressure isolation room, at 38 weeks of gestation. Testing the infant, showed elevated levels of IgG and IgM; cytokines and white blood cell count were also found to be elevated. Surprisingly, multiple rt-PCR tests taken on nasal swabs were found to be negative as well as chest CT showed no abnormalities. The breast milk was also tested and was found to be negative. [4]
The elevated IgM as reported was also found in another case series, wherein the infants were tested soon after birth. [5] In all these reports, the infants had good Apgar scores of 8-9 at 1 minute and 9-10 at 5 minutes, with no clinical signs of the disease. The elevated IgM levels and raised cytokine levels are a sign that intrauterine infection as IgM is not passed transplacentally. All the infants were kept isolated from their infected mothers and had negative rt-PCR tests.
In a study of 33 neonates in Wuhan born to COVID-19 positive mothers, 3 were found to be positive. As strict infection control procedures had been implemented at the time of birth, the source of infection was decided to be the mother, but it was uncertain if it was a vertical transmission as all bodily fluids tested were found to be negative. But it was a possibility which was not ruled out. [6]
But is this enough to pass a clinical judgment when a pregnant COVID-19 positive patient comes to you? Perhaps not, according to an editorial in JAMA [7] where Kimberlin et al asks us to be cautious, but not paranoid. IgM is not the most trusted assay to determine disease and could also be erroneous. As rt-PCR tests were negative, it is still uncertain if an intrauterine infection is a possibility or not, and more evidence is required before deciding any changes in treatment protocols.
So, if a mother comes to you worried about her child- reassure her. Take proper history and conduct a thorough physical examination to rule out COVID-19 exposure and if suspected, carry out nasopharyngeal swab collection and send it for testing. As a doctor, proper PPE, and maintenance of 1-meter distance from the patient are essential at all times. Protect yourselves from bodily fluids, which may spray or aerosolize the virus into the air around.
If a COVID-19 positive patient comes to you in pregnancy, explain to her about treatment and isolation. There is no indication currently for cesarean section unless it is an obstetric indication. There is no contraindication to breastfeeding too, but a proper face and hand hygiene must be maintained, and an N95 respirator must be worn by the mother at all times. Separation of the infant from the mother may have to be carried out, but that will be based on the clinical judgment of the managing team of doctors. The modality for testing severity of disease in the lungs is a chest CT, reticular ground-glass opacities are indicative of the spread of the disease in the lung parenchyma, and repeat CT scan can show worsening or the resolution of the infection.
Treatment in Pregnancy: Dos and Donts: [8]
1. Triage of pregnant women depending on their vital status must be done. Mild respiratory symptoms with stable vitals are admitted and kept under observation, whereas severe patients with SaO2 <93% and critical patients with organ failure must be managed immediately by a multidisciplinary team of an obstetrician, midwife, anesthetist, intensivist, microbiologist and neonatologist.
2. Supportive therapy by adequate hydration, rest and nutrition must be given. Depending on the severity of the disease, oxygen supplementation must be provided via high-flow nasal cannula.
3. Antiretroviral therapy of protease inhibitors- lopinavir/ritonavir combination is considered safe in pregnancy and has also shown efficacy against COVID-19 infection.
4. Pregnant women are also susceptible to secondary bacteria pneumonia post-viral infection, intravenous ceftriaxone can take care of it.
5. It is unclear whether corticosteroids should be used in such patients, but in certain cases, it can help ameliorate the ARDS. Again, clinical judgment can decide the course of action and treatment must be tailored based on individual patient history.
As can be clearly seen, a lot of clinical evidence is required to be able to come to a clear protocol for pregnant women who are infected with the novel coronavirus. Clinical assessment can only decide the course of action for each patient. A good history, proper precautions and a strong team of clinicians can help a woman transition seamlessly into motherhood.
Written by Devanshi Shah
References:
[1] WHO – Q&A on Covid-19, pregnancy, childbirth and breastfeeding
[2] David A. Schwartz (2020) 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. Archives of Pathology & Laboratory Medicine In-Press.
[3] American Journal of Roentgenology: 1-6. 10.2214/AJR.20.23072
[4] Dong L, Tian J, He S, et al. Possible Vertical Transmission of SARS-CoV-2
From an Infected Mother to Her Newborn. JAMA. Published online March 26,
2020. doi:10.1001/jama.2020.4621
[5] Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4861
[6] Zeng L, Xia S, Yuan W, et al. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr. Published online March 26, 2020. doi:10.1001/jamapediatrics.2020.0878
[7] Kimberlin DW, Stagno S. Can SARS-CoV-2 Infection Be Acquired In Utero? More Definitive Evidence Is Needed. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4868
[8] Liang, H. and Acharya, G. (2020), Novel corona virus disease (COVID‐19) in pregnancy: What clinical recommendations to follow?. Acta Obstet Gynecol Scand, 99: 439-442. doi:10.1111/aogs.13836
WHO’s official stand is that there is no higher risk in pregnancy of severe illness BUT because there are trials underway and due to the bodily changes in pregnancy, one can not know the extent of COVID-19 in these patients. [1] Due to the evolving crisis, we are seeing newer studies every day with new results. A study conducted in early February on 38 pregnant women showed that it did not lead to maternal deaths, and neither were there any confirmed cases of intrauterine transmissions, with rt-PCR being negative in all the neonatal specimens tested, hence leading to the belief that there is no intrauterine or transplacental transmission. [2] Even the CT scans done on pregnant women with COVID-19 positive samples, did not show major changes and recovered from pneumonia adequately. [3]
As the epidemic spread far and wide, in more countries, affecting a more diverse population, well into March, with it finally being declared a pandemic by WHO, studies started showing a change in trends. A mother in Wuhan, a 29-year-old primiparous female at 34 weeks of gestation, was detected to be COVID-19 positive after she was detected with symptoms, ground-glass opacities in her chest CT scan as well as a positive rt-PCR nasal swab. She gave birth to an infant girl by cesarean section in a negative pressure isolation room, at 38 weeks of gestation. Testing the infant, showed elevated levels of IgG and IgM; cytokines and white blood cell count were also found to be elevated. Surprisingly, multiple rt-PCR tests taken on nasal swabs were found to be negative as well as chest CT showed no abnormalities. The breast milk was also tested and was found to be negative. [4]
The elevated IgM as reported was also found in another case series, wherein the infants were tested soon after birth. [5] In all these reports, the infants had good Apgar scores of 8-9 at 1 minute and 9-10 at 5 minutes, with no clinical signs of the disease. The elevated IgM levels and raised cytokine levels are a sign that intrauterine infection as IgM is not passed transplacentally. All the infants were kept isolated from their infected mothers and had negative rt-PCR tests.
In a study of 33 neonates in Wuhan born to COVID-19 positive mothers, 3 were found to be positive. As strict infection control procedures had been implemented at the time of birth, the source of infection was decided to be the mother, but it was uncertain if it was a vertical transmission as all bodily fluids tested were found to be negative. But it was a possibility which was not ruled out. [6]
But is this enough to pass a clinical judgment when a pregnant COVID-19 positive patient comes to you? Perhaps not, according to an editorial in JAMA [7] where Kimberlin et al asks us to be cautious, but not paranoid. IgM is not the most trusted assay to determine disease and could also be erroneous. As rt-PCR tests were negative, it is still uncertain if an intrauterine infection is a possibility or not, and more evidence is required before deciding any changes in treatment protocols.
So, if a mother comes to you worried about her child- reassure her. Take proper history and conduct a thorough physical examination to rule out COVID-19 exposure and if suspected, carry out nasopharyngeal swab collection and send it for testing. As a doctor, proper PPE, and maintenance of 1-meter distance from the patient are essential at all times. Protect yourselves from bodily fluids, which may spray or aerosolize the virus into the air around.
If a COVID-19 positive patient comes to you in pregnancy, explain to her about treatment and isolation. There is no indication currently for cesarean section unless it is an obstetric indication. There is no contraindication to breastfeeding too, but a proper face and hand hygiene must be maintained, and an N95 respirator must be worn by the mother at all times. Separation of the infant from the mother may have to be carried out, but that will be based on the clinical judgment of the managing team of doctors. The modality for testing severity of disease in the lungs is a chest CT, reticular ground-glass opacities are indicative of the spread of the disease in the lung parenchyma, and repeat CT scan can show worsening or the resolution of the infection.
Treatment in Pregnancy: Dos and Donts: [8]
1. Triage of pregnant women depending on their vital status must be done. Mild respiratory symptoms with stable vitals are admitted and kept under observation, whereas severe patients with SaO2 <93% and critical patients with organ failure must be managed immediately by a multidisciplinary team of an obstetrician, midwife, anesthetist, intensivist, microbiologist and neonatologist.
2. Supportive therapy by adequate hydration, rest and nutrition must be given. Depending on the severity of the disease, oxygen supplementation must be provided via high-flow nasal cannula.
3. Antiretroviral therapy of protease inhibitors- lopinavir/ritonavir combination is considered safe in pregnancy and has also shown efficacy against COVID-19 infection.
4. Pregnant women are also susceptible to secondary bacteria pneumonia post-viral infection, intravenous ceftriaxone can take care of it.
5. It is unclear whether corticosteroids should be used in such patients, but in certain cases, it can help ameliorate the ARDS. Again, clinical judgment can decide the course of action and treatment must be tailored based on individual patient history.
As can be clearly seen, a lot of clinical evidence is required to be able to come to a clear protocol for pregnant women who are infected with the novel coronavirus. Clinical assessment can only decide the course of action for each patient. A good history, proper precautions and a strong team of clinicians can help a woman transition seamlessly into motherhood.
Written by Devanshi Shah
References:
[1] WHO – Q&A on Covid-19, pregnancy, childbirth and breastfeeding
[2] David A. Schwartz (2020) 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. Archives of Pathology & Laboratory Medicine In-Press.
[3] American Journal of Roentgenology: 1-6. 10.2214/AJR.20.23072
[4] Dong L, Tian J, He S, et al. Possible Vertical Transmission of SARS-CoV-2
From an Infected Mother to Her Newborn. JAMA. Published online March 26,
2020. doi:10.1001/jama.2020.4621
[5] Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4861
[6] Zeng L, Xia S, Yuan W, et al. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr. Published online March 26, 2020. doi:10.1001/jamapediatrics.2020.0878
[7] Kimberlin DW, Stagno S. Can SARS-CoV-2 Infection Be Acquired In Utero? More Definitive Evidence Is Needed. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4868
[8] Liang, H. and Acharya, G. (2020), Novel corona virus disease (COVID‐19) in pregnancy: What clinical recommendations to follow?. Acta Obstet Gynecol Scand, 99: 439-442. doi:10.1111/aogs.13836
Very well written. Informative and impressive.
ReplyDeleteDr. Sharat Kolke
Thank you! Please also read up the other articles we have published on this blog in our series on Covid-19. We hope to disseminate as much as knowledge as we can in these times of crisis!
DeleteVery informative, well written
ReplyDeleteWell written, very informative
ReplyDelete