Sars-cov-2 e Covid-19 -Artigos científicos: Atenção ao Recém-nascido

Atenção obstétrica no Reino Unido durante pandemia

Publicado no Best Practice & Research Clinical Obstetrics & Gynaecology

2. Labour and birth

Highlights

Infection prevention and control in intrapartum care is a priority.
Women who become unwell with COVID-19 are at higher risk of iatrogenic preterm birth and have higher than normal rates of caesarean section.
Maintaining choice of place of birth, providing high quality care and support and pain relief should also remain a priority.
Care should be taken to enable women to have access to their partner or support person and remain with their newborn.

Abstract

This chapter describes the national guidance for care during labour and childbirth in the United Kingdom during the COVID-19 pandemic. The content largely draws attention on the guidance developed by the Royal College of Obstetricians (RCOG) and the Royal College of Midwives (RCM), and specific guidance on infection prevention and control measures from Public Health England.

The key areas addressed are as follows:

Testing of pregnant women before and on admission for labour and birth
Overall approach to intrapartum care for women with and without symptoms of COVID-19
Timing, place, and type of birth considerations
Personal Protective Equipment (PPE) during labour and birth – for staff, women, and birth supporters
Use of birthing pools and waterbirth
Foetal monitoring
Immediate care of the newborn and support for breastfeeding.

The chapter refers to some of the ways in which the guidance was translated in practice.

The guidance was developed using a rapid analysis approach to emerging research and evidence, along with evidence from previous experiences of coronavirus combined with consensus expert opinion from all key professionals providing maternity care in the UK.

What is known

The UK RCOG/RCM COVID-19 guidance was widely accepted across the UK maternity services and also worldwide as a reliable and credible source of information to shape care during the pandemic.

What is not known

The full impact of the pandemic on the experiences and outcomes for babies and women of pregnancy, childbirth, and early parenting in the UK.

The impact of the new approaches to intrapartum care on experiences and outcomes for women, babies, and families.

The impact of the changes required to intrapartum care as a result of the pandemic on the professional care provided; in terms of pressure created by rapidly changing approaches to care and restrictions on the ability to provide normal levels of care.

Keywords

COVID-19
Pandemic
Intrapartum care
Foetal monitoring
Waterbirth
Skin to skin

Research Update on COVID-19 and Pregnancy

Da Newsletter da Evidence Based Birth

 

Hello

It’s been 6 weeks since our last COVID-19 and pregnancy newsletter.

In this edition of the Evidence Based Birth® COVID-19 Newsletter, we provide a new overview of the research on COVID-19 and pregnancy to date, focusing on key findings and recommendations.

**Feel free to forward this email to any friends, family, clients, or colleagues who might find it helpful. If you’re a healthcare worker, feel free to print this off to share at the nurse’s station! Anyone can subscribe to receive these updates by visiting evidencebasedbirth.com/covid19

The archive of this newsletter will also be posted on that page.

Today’s questions (answered in a Q&A section at the bottom of this email) include:

  • Do we know what the overall pre-term birth rate was in the U.S. for 2020, and how that might compare to other years?
  • I have a history of COVID in early pregnancy, and now my doctor is recommending that I take either aspirin or an anticoagulant for the rest of pregnancy. Is there any research on this?

To ask a question for consideration for future newsletters, submit your question here.

Don’t forget that our COVID-19 resource & pregnancy page includes archives of these newsletters (including past Q & A’s), a sample informed consent form to refuse mother-newborn separation, our virtual doula directory, a free birthing crash course, a link to find our comprehensive EBB Childbirth Class online, and other info you might find useful. You can access that page here.


Research Update for January 21, 2021

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19).
  • Black, Latinx, and Indigenous pregnant and nonpregnant individuals are bearing the burden of the pandemic. These groups have higher rates of COVID-19 infections, hospitalizations, and severe outcomes, including death. Racial and ethnic health inequity in the pandemic is due to long-standing structural racism that put brown and black bodies at increased risk of getting sick and dying—not because of their biology, but because of discrimination in all sectors of life (aka systemic racism).

Numbers Update from Johns Hopkins University

As of January 21, 2021, there are over 96 million confirmed and probable cases of COVID-19 around the world. The highest number of cases is still in the U.S. (over 24 million), followed by India, Brazil, Russia, the United Kingdom, France, Italy, Turkey, Spain, and Germany.

Prevention

  • Pregnant people are advised to follow the same recommendations as nonpregnant people for avoiding exposure to SARS-CoV-2. These recommendations from the CDC include:
    • Wear a mask over your nose and mouth
    • Stay 6 feet away from people who don’t live in your household
    • Avoid crowded places
    • Meet in outdoor spaces when possible and try to ventilate indoor spaces
    • Wash hands often
    • Cover coughs and sneezes
    • Clean and disinfect frequently touched surfaces
    • Be alert for symptoms of COVID-19
  • Prenatal and postpartum care appointments are important to keep; however, depending on your individual circumstances, it might be appropriate to delay some appointments or meet virtually. Elective ultrasounds are not recommended (ACOG, 2020). GBS screening is still recommended between 36 weeks, 0 days and 37 weeks, 6 days of pregnancy. However, some care settings are giving people instructions on how to self-collect a vaginal-rectal swab to limit in-person exposure during the pandemic (ACOG, 2020).

Vaccines

  • Many vaccines are being developed, but pregnant and lactating individuals have been excluded from every trial so far. This means we do not have any data yet on the maternal, fetal, or newborn effects of these vaccines.
  • The two vaccines that are currently authorized and recommended to prevent COVID-19 in the U.S. are the Pfizer-BioNTech vaccine and Moderna’s vaccine. They are both messenger RNA (mRNA) vaccines that do not contain live virus.
  • In the U.S., the SMFM (12/21), ACOG (12/21), and the CDC (12/28) recommended that COVID-19 vaccines should not be withheld from pregnant/lactating individuals who are otherwise eligible for the vaccine and desire vaccination.
  • In the U.K., on December 3, the Joint Committee on Vaccination and Immunization initially stated “JCVI favours a precautionary approach, and does not currently advise COVID-19 vaccination in pregnancy.” However, the JCVI updated their guidance on December 30 and now advises that “extremely clinically vulnerable” pregnant people discuss the option of vaccination with their care provider. They listed specific underlying conditions that put pregnant people at very high risk of experiencing serious complications from COVID-19:
    • Solid organ transplant recipients
    • Those with severe respiratory conditions including cystic fibrosis and severe asthma
    • Those who have homozygous sickle cell disease
    • Those receiving immunosuppression therapies sufficient to significantly increase risk of infection
    • Those receiving dialysis or with chronic kidney disease (stage 5)
    • Those with significant congenital or acquired heart disease
  • The JCVI also now advises that pregnant health care workers and pregnant workers in residential facilities can discuss the option of vaccination. In addition, they say that breastfeeding/chestfeeding parents should be offered vaccination if they are otherwise eligible.
  • The Royal College of Obstetricians & Gynecologists released a handout on COVID-19 vaccination and pregnancy (1/12/21). You can access this vaccine info sheet here.

Clinical Symptoms and Testing

  • COVID-19 symptoms are similar between pregnant and nonpregnant patients; however, some symptoms with infection appear to be less common during pregnancy, especially fever.
  • The U.S. PRIORITY study (Pregnancy CoRonavIrus Outcomes RegIsTrY) is an ongoing prospective nationwide study in the United States of pregnant or recently pregnant people. The most common symptoms in 594 symptomatic patients who tested positive for SARS-CoV-2 infection were cough (20%), sore throat (16%), body aches (12%), and fever (12%) (Afshar et al. 2020). Half of everyone had their symptoms resolve by 37 days, but symptoms lasted for ≥8 weeks in 25% of PRIORITY participants. In the PRIORITY study, 95% of participants were outpatients. The researchers are working to increase enrollment of Latina, Black, and Native American patients. These groups are currently underrepresented in the study (60% of study participants are White) which limits generalizability.
  • Data from the CDC that included more hospitalized pregnant people with COVID-19 show increased rates of symptoms (50% had cough, 32% had fever, 37% had muscle aches, 24% has chills, 43% had headache, 26% head shortness of breath, 28% had sore throat, 14% had diarrhea, 20% had N/V, 8% had abdominal pain, 13% had runny nose, 22% had new loss of taste or smell, 14% had fatigue, 2% had wheezing, and 4% had chest pain (Zambrano et al. 2020).
  • To treat fever and pain, acetaminophen (Tylenol) is preferred over NSAIDs (aspirin, ibuprofen/Motrin/Advil) because of possible worsening of symptoms with COVID-19 (Berghella and Hughes, 2020). Low-dose aspirin is still recommended for preeclampsia prevention as medically indicated, but may not be appropriate for pregnant and recently pregnant patients with suspected or confirmed COVID; care should be individualized (ACOG, 2020).
  • Systematic reviews suggest that the majority of pregnant people who test positive during universal screening are without symptoms (most asymptomatic, but some pre-symptomatic) (Berghella and Hughes, 2020).
  • COVID-19 diagnosis is done with nucleic acid amplification testing (NAAT), most commonly with a reverse-transcription polymerase chain reaction (RT-PCR) assay, which detects SARS-CoV-2 RNA from the upper respiratory tract. PCR tests are considered the gold standard for testing.
  • Antigen tests are another type of diagnostic test. They detect a specific protein in SARS-CoV-2. Antigen tests are sometimes used first, but these tests are less sensitive, so negative antigen tests should usually be confirmed with NAAT if there is clinical suspicion of COVID-19. The majority of rapid tests so far have been antigen tests; however, there are now rapid PCR-based tests available in some care settings.
  • False-negative tests are possible, so a negative RT-PCR test may need to be repeated if there is high clinical suspicion of COVID-19.
  • False-positives have also been reported, but they are thought to be less common than false-negatives.

Maternal Outcomes

  • There is no evidence that pregnancy increases the risk of getting infected with SARS-CoV-2
  • Definitions according to the National Institutes of Health:
    • Mild illness is considered symptoms without difficulty breathing or abnormal chest imaging
    • Moderate illness is evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SaO2) ≥94% on room air at sea level.
    • Severe illness is respiratory frequency >30 breaths per minute, SaO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300, or lung infiltrates >50%
    • Critical illness is respiratory failure, septic shock, and/or multiple organ dysfunction
  • Most (>90%) of people infected during pregnancy recover before they give birth and without needing hospitalization for COVID-19 (Berghella and Hughes, 2020). It is reassuring that the majority of pregnant people with COVID-19 either have no symptoms or mild illness that does not require hospitalization.
  • However, pregnancy has been shown to increase the risk of severe or critical COVID-19. Given the growing evidence, the CDC now includes pregnant people in its “increased risk” category for COVID-19 illness. Unfortunately, the evidence in limited by large amounts of missing data on pregnancy status, race/ethnicity, and info on symptoms and underlying medical conditions (Zambrano et al. 2020).
  • According to the latest U.S. surveillance data from the CDC (with over 400,000 symptomatic females of reproductive age), pregnant people with symptomatic COVID-19 appear to be at increased risk for ICU admission, invasive ventilation, extracorporeal membrane oxygenation (ECMO, a life support machine) and death compared to nonpregnant females of the same age with symptomatic COVID-19 (Zambrano et al. 2020). Still, the absolute risk of severe or critical illness and death for pregnant patients is low—even lower than the absolute risk of these outcomes during the H1N1 influenza pandemic (ACOG, 2020).
  • In the CDC analysis, the absolute risks for invasive ventilation and death for pregnant versus nonpregant people of the same age and sex were 2.9 versus 1.1 per 1,000 and 1.5 versus 1.2 per 1,000, respectively. ECMO was used rarely but at a higher rate with pregnancy (0.7 versus 0.3 per 1,000). The absolute risk of ICU admission was noticeably increased (10.5 versus 3.9 per 1,000); however, this may be due in part to differences in care management during pregnancy.
  • Remember, these absolute risks apply to people with lab-confirmed, symptomatic COVID-19; we don’t know if the risk of these outcomes is increased during pregnancy for people with asymptomatic infection or with symptoms that are so mild they do not seek medical care.
  • Risk factors for severe or critical COVID-19 during pregnancy are similar to the risk factors in the general population (Westnedge et al. 2021). They include age ≥35 years, BMI ≥30, hypertension, and diabetes (preexisting and gestational) (Allotey et al. 2020; ACOG, 2020).
  • Importantly, Black and Hispanic individuals who are pregnant are disproportionately affected by COVID-19—not because of their biology, but because of systemic racism creating inequitable opportunities for health.
  • Timing of birth with COVID-19 should be individualized. Importantly, COVID-19 infection is not an indication for Cesarean, induction, or operative vaginal birth. When possible, it’s best to wait to give birth until after testing negative. Then, there is less chance of passing the infection to health care workers and to the newborn in the postpartum period.
  • However, people with term pregnancies who have mild COVID-19 may wish to give birth sooner rather than later to avoid the risk of giving birth with more severe COVID-19 (should the disease worsen).
  • Severely ill patients at least 32 weeks of pregnancy with COVID-19 pneumonia may benefit from early birth. But it’s not clear whether giving birth improves the birthing person’s respiratory disease (Berghella and Hughes, 2020).
  • Maternal COVID-19 is linked to an increased risk of Cesarean. A report from the UK Obstetric Surveillance System (UKOSS) on pregnant people admitted to the hospital with confirmed COVID-19 in the UK found that 59% of people gave birth by Cesarean (Knight et al. 2020). About half of these were for maternal or fetal compromise and half were for other obstetric reasons (e.g., progress in labor, planned repeat Cesarean).
  • A large systematic review estimated that about 65% of pregnant people with suspected or confirmed COVID-19 gave birth by Cesarean (Allotey et al. 2020). Many of the studies in this review (24/77) came from China, where the Cesarean rate with COVID-19 was very high early in the pandemic.
  • U.S. surveillance data of pregnant people with laboratory-confirmed SARS-CoV-2 infection reported that among nearly 4,000 birthing people, the overall Cesarean rate was 34%, which is slightly higher than the U.S. Cesarean rate in 2019 (32%) (Berghella and Hughes, 2020).
  • Wider implications of the pandemic for maternal health include increased risk of mental health distress and intimate partner violence. Care providers should be on heightened alert for these issues and look for ways to help clients manage stress, anxiety, and depression.

Newborn Outcomes

  • Maternal COVID-19 has been linked to an overall increased risk of preterm birth, although individual countries have reported seeing decreased rates of preterm birth or no change in preterm birth rates.
  • A systematic review of 77 studies from more than a dozen different countries, including over 11,000 pregnant and recently pregnant people with suspected or confirmed COVID-19, estimated that about 17% of births were preterm (Allotey et al. 2020). This was a three times greater risk of preterm birth with COVID-19 compared to those without the disease. However, most of these preterm births were medically caused (iatrogenic). The spontaneous preterm birth rate was only 6%, which is similar to the rate observed before the pandemic. It’s thought that complications from COVID-19 (e.g., pneumonia) increase the risk of Cesarean and preterm birth because providers intervene in hopes of improving the maternal respiratory condition. However, there is no evidence that planned early birth improves maternal outcomes with severe or critical COVID-19 (Berghella and Hughes, 2020).
  • U.S. surveillance data of pregnant people with laboratory-confirmed SARS-CoV-2 infection reported that among 3,912 live births with known gestational age, 12.9% were preterm (<37 weeks) (Woodworth et al. 2020). This rate is higher than the reported 10.2% among the general U.S. population in 2019. Please see the Q&A section at the bottom of this newsletter for more discussion of pre-term birth rates during the pandemic.
  • The U.S. PRIORITY study has, so far, not detected a difference in poor outcomes, including preterm birth, NICU admission, and respiratory disease, between infants (n=263) born to birthing parents testing positive (n=179) versus those testing negative (n=84) (Flaherman et al. 2020). A study with more racial and ethnic diversity also did not detect a difference in poor outcomes (using a combined outcome of preterm birth, severe preeclampsia, or Cesarean for abnormal GHR) by maternal COVID-19 status (Adhikari et al. 2020).
  • There is no evidence suggesting an increased risk of congenital anomalies or any problems with the baby’s development.
  • There is also no evidence suggesting that infection in early pregnancy increases the risk of miscarriage. (Data on first and second trimesters are limited.)
  • Vertical transmission (transmission from the pregnant person to the baby before or during birth) has been reported in a few cases but it is thought to be rare. Researchers still do not understand the mechanisms by which vertical transmission occurs (Westnedge et al. 2021). A few placental infections and very early newborn infections have been reported; however, most placentas studied so far had no evidence of infection. Importantly, there is no evidence that the risk of vertical transmission is affected by mode of birth, method of feeding or rooming in. The vast majority (over 95%) of newborns born to infected parents have been asymptomatic or with only mild infection at birth. It is reassuring that severe or critical COVID-19 is rare with newborns (Westnedge et al. 2021).
  • A large U.S. observational study found that the rate of early newborn infection among infants born to a parent who tested positive was 3%; most of the infected babies were born to parents with no symptoms or mild symptoms (Adhikari et al. 2020).
  • There is no evidence that the risk of stillbirth increases with COVID-19 infection; however, the risk does appear to increase among patients hospitalized with a COVID-19 infection.
  • Analysis of hospitalization data from England did not show an increase in stillbirths in England during the pandemic when compared with the same months in the previous year (Stowe et al. 2020).
  • In the U.S., data from the CDC show a higher stillbirth rate among pregnant people hospitalized with COVID-19 compared to the overall population of pregnant people with lab-confirmed infection (3% versus 0.4%) (Panagiotakopoulos et al. 2020; Woodworth et al. 2020). For comparison, the overall rate of stillbirth in the U.S. is 0.6%. The increase in stillbirth among hospitalized COVID-19 patients may be related to maternal illness, medical intervention to treat COVID-19, and/or disruptions in prenatal care during the pandemic.
  • There have been reports of problems with placental function from COVID-19 infection. However, more data is needed before we know how widespread a problem this is, and whether it’s clinically significant.

Treatment

  • Corticosteroid use to help prevent preterm birth is likely safe for pregnant people with COVID-19, and corticosteroid use for severe or critical maternal COVID-19 may also be beneficial (Westnedge et al. 2021).
  • ACOG recommends that dexamethasone, a corticosteroid, be used for pregnant people with COVID-19 who are receiving supplemental oxygen or are mechanically ventilated, and that dexamethasone should not be withheld for treatment of COVID-19 due to pregnancy status.
  • Similarly, UpToDate guidance for clinicians advises that “In pregnant women who meet criteria for use of glucocorticoids for maternal treatment of COVID-19 and also meet criteria for use of antenatal corticosteroids for fetal maturity, we suggest administering the usual doses of dexamethasone (four doses of 6 mg given intravenously 12 hours apart) to induce fetal maturation and continue dexamethasone to complete the course of maternal treatment for COVID-19 (6 mg orally or intravenously daily for 10 days or until discharge, whichever is shorter).”
  • The evidence for dexamethasone treatment comes from the RECOVERY trial, a large, multicenter, RCT for patients hospitalized with COVID-19 in the U.K. (RECOVERY Collaborative Group et al. 2020). The trial showed that dexamethasone resulted in lower 28-day mortality among people receiving either mechanical ventilation or oxygen but not among those receiving no respiratory support. Even though only six pregnant people were included in the trial, guidance supports dexamethasone for use with infected pregnant people who are receiving supplemental oxygen or are mechanically ventilated because of possible life-saving benefits.
  • Pregnancy is a hypercoagulable state (meaning there is an increased tendency toward blood clotting), so people who are pregnant or in the postpartum period have increased risk of thromboembolism (a blood clot that is carried by the blood stream and plugs a blood vessel) compared with nonpregnant people (ACOG, 2020). COVID-19 is also linked to increased blood clotting and increased risk of thromboembolism, especially in ICU patients. Therefore, recommendations are that pregnant patients hospitalized with severe or critical COVID-19 should be treated with prophylactic-dose anticoagulation, if there are no contraindications to its use (ACOG, 2020; Berghella and Hughes, 2020). Clinicians should also have a low threshold for investigating possible thromboembolic events in COVID-19 patients during pregnancy and postpartum (Westnedge et al. 2021). Please see the Q&A section at the bottom of this newsletter for more discussion of anticoagulant drugs.
  • Remdesivir, an antiviral medication, is recommended for pregnant patients who would otherwise be candidates for the treatment. It has been used with severely ill pregnant patients without causing harm to the fetus (Berghella and Hughes, 2020).

Giving Birth

  • ACOG guidelines suggest, “In both the inpatient and outpatient settings, it is recommended that the number of visitors be reduced to the minimum necessary, for example, those essential for the pregnant individual’s well-being (emotional support persons).” Importantly, they say, “Labor, delivery, and postpartum support may be especially important to improve outcomes for individuals from communities traditionally underserved or mistreated within the health care system. In considering visitation policies, institutions should be mindful of how restrictions might differentially and negatively affect these communities, which in many areas are also disproportionately affected by COVID-19.”
  • Professional guidelines acknowledge that it may not be feasible to wear a mask during labor, especially during second stage labor (ACOG, 2020). Wearing a mask could make pushing difficult and forceful exhalation may also make the mask significantly less effective. For this reason, those caring for birthing people should use appropriate PPE.
  • Delayed cord clamping is still best practice when the birthing parent has COVID-19 (ACOG, 2020). The cord should remain unclamped for up to five minutes or when cord pulsation ceases. There is no evidence that delayed cord clamping increases the risk of giving the virus to the baby, and there are substantial known risks to early cord clamping. The care provider should wear appropriate PPE.

Rooming in and Infant Feeding

  • There are many established benefits to rooming in, including increased success breastfeeding and parent-infant bonding. Studies have not found a difference in the rate of transmission when newborns are separated from infected parents versus kept together in the same room. Guidelines now state that newborns should “ideally” be kept together with their infected parent, and that “Decisions about temporary separation should be made in accordance with the mother’s wishes.” (ACOG, 2020).
  • Birthing parents with COVID-19 should be encouraged to breastfeed/chestfeed, but should wear PPE (Westnedge et al. 2021). It is not known whether the virus can be transmitted through breastmilk. One case report detected SARS-CoV-2 RNA in breastmilk, but the viral particles may not have been infectious; most breastmilk samples from positive parents have been negative.
  • Healthy, uninfected birthing parents and newborns are advised to consider early hospital discharge after birth (after 1 day with uncomplicated vaginal births and after 2 days with Cesarean births depending on recovery status) (ACOG, 2020).

Professional Guidance and Clinical Recommendations

  • Several professional organizations have issued guidance on pregnancy issues during the pandemic. You can access professional guidance at acog.orgSMFM.org, and rcog.org.uk.
  • Also, UpToDate.com has made their COVID-19 content free. They have a page devoted to COVID-19 and pregnancy.

Q & A Section

Question: Do we know what the overall pre-term birth rate was in the U.S. for 2020, and how that might compare to other years?

Answer: No, the most recent year of birth data from the U.S. Centers for Disease Control (CDC) is 2019. The CDC National Center for Health Statistics (NCHS) released their latest data brief (No. 387) in October 2020 with key findings from the 2019 data. The overall rate of preterm birth rose to 10.23% in 2019, an increase over the 2018 rate of 10.02%.

We don’t know yet if the U.S. preterm birth rate rose in 2020, although early findings suggest that it may have. The CDC has been collecting info on pregnancy and infant outcomes among pregnant people with lab-confirmed infections through SET-NET (the Surveillance for Emerging Threats to Mothers and Babies Network). Among 3,912 live births to infected parents, 12.9% were preterm (<37 weeks) (Woodworth et al. 2020). As you can see, this is higher than the U.S. preterm birth rate among the general population in 2018 and 2019, and if enough pregnant people experienced infection, this could possibly contribute to a higher preterm birth rate in 2020.

Individual studies have been mixed on whether they found a difference in preterm births during the pandemic. Decreases in preterm births have been reported in several European countries, sometimes alongside increases in stillbirth. But even within countries, the impact of the pandemic on preterm birth likely varies in sub-populations based on social and economic factors.

Question: I have a history of COVID in early pregnancy, and now my doctor is recommending that I take either aspirin or an anticoagulant for the rest of pregnancy. Is there any research on this or guidelines to support this practice?

Answer: We have not seen any evidence to support the prophylactic (preventative) use of aspirin among pregnant people with a history of COVID-19 earlier in pregnancy but without other clinical indications for the treatment. However, recommendations mention that aspirin should continue to be offered to pregnant and postpartum parents as medically indicated during the pandemic (ACOG, 2020). Perhaps your doctor is recommending aspirin for a non-COVID related medical indication? Low-dose aspirin is most commonly recommended during pregnancy to pregnant people at moderate to high risk of preeclampsia.

As we mentioned earlier in this newsletter, aspirin may not be appropriate for pregnant people with suspected or confirmed COVID-19 because of evidence that NSAIDs (including aspirin) potentially worsen COVID symptoms.

We are also not aware of any evidence (yet) to support thromboprophylaxis with anticoagulants among pregnant people with a history of COVID-19 earlier in pregnancy but without other clinical indications for the treatment. People with active COVID-19 infections during pregnancy (particularly with severe or critical disease) may benefit from anticoagulation treatment, but the treatment is only recommended for those who are hospitalized because of their COVID-19 disease (Berghella and Hughes, 2020). People hospitalized because of their COVID-19 infections may be advised to continue thromboprophylaxis for 10 days following hospital discharge or longer if they remain ill from their infection. But if you had COVID-19 in early pregnancy and it did not require hospitalization, then your doctor may be recommending anticoagulants because you have non-COVID related risk factors for blood clots (also known as venous thromboembolisms, or VTEs).

Whenever care providers recommend intervention, you should always feel empowered to ask them if their advice is based on a research study, a clinical guideline, or their professional medical opinion. Also, keep in mind that as the pandemic progresses, new research may come out that provides us with new insights on this topic.

This concludes the research update for January 21, 2021. We hope you found it helpful! Our next research update will come out in March 2021.

If you would like to submit a follow-up question for our consideration to include in upcoming newsletters, you can submit your question here.

Sincerely,

The Research Team at Evidence Based Birth®


References

Adhikari, E. H., Moreno, W., Zofkie, A. C., et al. Pregnancy Outcomes Among Women With and Without Severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAMA Netw Open. 2020;3(11):e2029256. Click here.

Afshar, Y., Gaw, S. L., Flaherman, V. J., et al. (2020). Clinical Presentation of Coronavirus Disease 2019 (COVID-19) in Pregnant and Recently Pregnant People. Obstet Gynecol. 2020 Dec;136(6):1117-1125. Click here.

Allotey, J., Stallings, E., Bonet, M., et al… for PregCOV-19 Living Systematic Review Consortium (2020). Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ (Clinical research ed.), 370, m3320. Click here.

American College of Obstetricians and Gynecologists (2020). COVID-19 FAQs for obstetricians-gynecologists, obstetrics. Washington, DC: ACOG. Available at: https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Retrieved January 7, 2020.

Berghella, V. and Hughes, B. (2020). UpToDate: Coronavirus disease 2019 (COVID-19): Pregnancy Issues and Antenatal care. Click here.

Flaherman, V. J., Afshar, Y., Boscardin, W. J., et al. (2020). Infant Outcomes Following Maternal Infection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): First Report From the Pregnancy Coronavirus Outcomes Registry (PRIORITY) Study, Clinical Infectious Diseases, ciaa1411. Click here.

Knight, M., Bunch, K., Vousden, N., et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 2020; 369:m2107. Click here.

Panagiotakopoulos, L., Myers, T. R., Gee, J., et al. (2020). SARS-CoV-2 Infection Among Hospitalized Pregnant Women: Reasons for Admission and Pregnancy Characteristics — Eight U.S. Health Care Centers, March 1–May 30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1355–1359. Click here.

RECOVERY Collaborative Group, Horby, P., Lim, W. S., et al. (2020). Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020 Jul 17:NEJMoa2021436. Click here.

Stowe, J., Smith, H., Thurland, K., et al. (2020). Stillbirths During the COVID-19 Pandemic in England, April-June 2020. JAMA 2020. Click here.

Wastnedge, E. A. N., Reynolds, R. M., van Boeckel, S. R., et al. (2021). Pregnancy and COVID-19. Physiol Rev. 2021 Jan 1;101(1):303-318. Click here.

Woodworth, K. R., CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team, COVID-19 Pregnancy and Infant Linked Outcomes Team (PILOT), et al. (2020). Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy – SET-NET, 16 Jurisdictions, March 29-October 14, 2020. MMWR Morb Mortal Wkly Rep. 2020 Nov 6;69(44):1635-1640. Click here.

Zambrano, L. D., Ellington, S., Strid, P., CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team, et al. (2020). Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status – United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020 Nov 6;69(44):1641-1647. Click here.

Covid-19 e morte fetal no primeiro trimestre

 

Texto de Melania Amorim

@melania44 

・・・
COVID-19 e morte fetal no primeiro trimestre
A doença por coronavírus 2019 (COVID-19) é causada pela infecção do trato respiratório por SARS-CoV-2, que sobrevive nos tecidos durante o curso clínico da infecção, mas há evidências limitadas de infecção placentária e transmissão vertical de SARS-CoV-2 . O impacto da COVID-19 na gravidez de primeiro trimestre permanece pouco compreendido. Além disso, não se sabe por quanto tempo o SARS-CoV-2 pode sobreviver na placenta.
Aqui, relatamos o caso de uma mulher grávida no primeiro trimestre que apresentou resultado positivo para SARS-CoV-2 com 8 semanas de gestação, embora seu curso clínico tenha sido assintomático. Na 13ª semana de gestação, seu esfregaço de garganta testou negativo para SARS-CoV-2, mas o RNA viral foi detectado na placenta e as proteínas Spike (S) (S1 e S2) foram imunolocalizadas no citotrofoblasto e células sincitiotrofoblastas das vilosidades placentárias.
Histologicamente, as vilosidades eram geralmente avasculares com deposição de fibrina peri-vilositária e em algumas áreas a camada de sincitiotrofoblasto parecia lisada. A decídua também apresentava deposição de fibrina com extensa infiltração leucocitária sugestiva de inflamação.
O SARS-CoV-2 cruzou a barreira placentária, pois o RNA viral foi detectado no líquido amniótico e as proteínas S foram detectadas na membrana fetal. A ultrassonografia revelou edema subcutâneo extenso com derrame pleural sugestivo de hidropisia fetal e a ausência de atividade cardíaca indicou morte fetal.
Este é o primeiro estudo a fornecer evidências concretas de infecção placentária persistente de SARS-CoV-2 e sua transmissão congênita associada com hidropisia fetal e morte fetal intrauterina no início da gravidez.

Infant Outcomes Following Maternal Infection with SARS-CoV-2: First Report from the PRIORITY Study

Nesse recente estudo (PRIORITY), disponível na página neonatal www.paulomargotto.com.br, com uma coorte de 263 bebês, incluindo 179 e 84, respectivamente, nascidos de mães com teste positivo ou negativo para SARS CoV-2, mostrou que o risco de infecção pelo bebê foi de 1,1% (e os sintomas foram mínimos). Sem complicações nas 6-8semanas. Na discussão desse estudo trouxemos informações de uma das maiores coorte dos Estados Unidos de neonatos nascidos de mães com teste positivo para SARS-CoV-2 no momento do parto e que foram subsequentemente acompanhadas com testes seriados e clinicamente até 1 mês de vida. Oitenta e dois neonatos (68%) completaram o acompanhamento no dia 5–7 de vida. Dos 82 neonatos, 68 (83%) ficaram com as mães. Todas as mães foram autorizadas a amamentar; com 5 a 7 dias de vida, 64 (78%) ainda estavam amamentando. 79 (96%) de 82 neonatos tiveram uma repetição da PCR em 5–7 dias de vida, que foi negativa em todos; 72 (88%) neonatos também foram testados com 14 dias de vida e nenhum foi positivo. Nenhum dos neonatos apresentou sintomas de COVID-19. Assim, o o Alojamento Conjunto com a mãe e a amamentação são seguros se associados à educação adequada dos pais sobre práticas seguras de controle de infecção, como o uso de máscaras cirúrgicas em todos os momentos e a higienização frequente das mãos.

 

Abstract

Infant outcomes after maternal SARS-CoV-2 infection are not well-described. In a prospective U.S. registry of 263 infants born to mothers testing positive or negative for SARS-CoV-2, SARS-CoV-2 status was not associated with birth weight, difficulty breathing, apnea or upper or lower respiratory infection through 8 weeks of age.

Keywords: COVID-19; Newborn; Pregnancy; SARS-CoV-2.

 

Transplacental transmission of SARS-CoV-2 infection

Transplacental transmission of SARS-CoV-2 infection

Publicado originamente no Nature (em inglês). DOI: 10.1038/s41467-020-17436-6

Abstract

SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.

Introduction

SARS-CoV-2 infection causes the new coronavirus disease (COVID-19) and is mainly transmitted through droplets, but other transmission routes have been hypothesized. Some cases of perinatal transmission have been described1,2,3,4,5,6, but it is unclear if these occurred via the transplacental or the transcervical route or through environmental exposure. It is important to clarify whether and how SARS-CoV-2 reaches the fetus, so as to prevent neonatal infection, optimize pregnancy management and eventually better understand SARS-CoV-2 biology. Here we present a comprehensive case study demonstrating the transplacental transmission of SARS-CoV-2 with clinical manifestation in the neonate, consistent with neurological signs and symptoms of COVID-19.

Results

Case study

A 23-year-old, gravida 1, para 0 was admitted to our university hospital in March 2020 at 35+2 weeks of gestation with fever (38.6 °C) and severe cough and abundant expectoration since 2 days before hospitalisation. Real-time polymerase chain reaction (RT-PCR) was performed as described in the “Methods” below: both the E and S genes of SARS-CoV-2 were detected in blood, and in nasopharyngeal and vaginal swabs. Pregnancy was uneventful and all the ultrasound examinations and routine tests were normal until the diagnosis of COVID-19. Thrombocytopenia (54 × 109/L), lymphopenia (0.54 × 109/L), prolonged APTT (60 s), transaminitis (AST 81 IU/L; ALT 41 IU/L), elevated C-reactive protein (37 mg/L) and ferritin (431 μg/L) were observed upon hospital admission. Three days after admission a category III-fetal heart rate tracing7 (Fig. 1) was observed and therefore category II-cesarean section (i.e., fetal compromise; not immediately life-threatening, https://www.rcog.org.uk/globalassets/documents/guidelines/goodpractice11classificationofurgency.pdf) was performed, with intact amniotic membranes, in full isolation and under general anesthesia due to maternal respiratory symptoms. Clear amniotic fluid was collected prior to rupture of membranes, during cesarean section and tested positive for both the E and S genes of SARS-CoV-2. Delayed cord clamping was not performed as its effect on SARS-CoV-2 transmission is unknown. The woman remained hospitalized for surveillance of her clinical conditions and finally she was discharged in good conditions, 6 days after delivery.

Fig. 1: Illustrative snapshot of fetal heart rate tracing.
figure1

Tachycardia, absent baseline variability, absence of accelerations with recurrent prolonged and late decelerations. These findings are highly suggestive of a pathological category III fetal heart rate tracing7, which is strongly associated with adverse neonatal outcome. This cardiotogram was recorded 26 min before the cesarean section.

A male neonate was delivered (gestational age 35+5 weeks; birth weight 2540 g). Apgar scores were 4 (in detail: heart rate = 1, respiratory activity = 1, skin color = 1, muscular tonus = 1, remaining items were coded zero), 2 (in detail: skin color = 1, muscular tonus = 1, remaining items were coded zero) and 7 (in detail: heart rate = 2, respiratory activity = 2, skin color = 2, muscular tonus = 1) at 1, 5 and 10 min, respectively. Neonatal resuscitation was provided according to current international guidelines8 (face mask-delivered non-invasive ventilation from birth until 5 min of life and then intubation and invasive ventilation with inspired oxygen fraction titrated up to 0.30; monitoring included ECG, end-tidal side-stream CO2 measurements, peripheral oxygen saturation and perfusion index). The neonate was eventually transferred in full isolation to the neonatal intensive care unit (NICU) in a negative pressure room. Cord blood gas analysis showed normal pH and lactate. The neonate did not receive any sedative or analgesic drug and was monitored according to our routine NICU protocols for post-resuscitation care: Sarnat score, point-of-care echocardiography and lung ultrasound9 were normal upon NICU admission. Vital parameters were always normal and the baby was extubated after ~6 h. Before the extubation, blood was drawn for capillary blood gas analysis (at 1.5 h of life) and routine blood tests, which yielded normal values. Moreover, before the extubation, blood and non-bronchoscopic bronchoalveolar lavage fluid were collected for RT-PCR and both were positive for the E and S genes of SARS-CoV-2. Lavage was performed using a standardized procedure10 as detailed below. Blood culture was negative for bacteria or fungi. Nasopharyngeal and rectal swabs were first collected after having cleaned the baby at 1 h of life, and then repeated at 3 and 18 days of postnatal age: they were tested with RT-PCR and were all positive for the two SARS-CoV-2 genes. Routine blood tests (including troponin, liver and kidney function) were repeated on the second day of life and resulted normal. Feeding was provided exclusively using formula milk.

On the third day of life, the neonate suddenly presented with irritability, poor feeding, axial hypertonia and opisthotonos: cerebrospinal fluid (CSF) was negative for SARS-CoV-2, bacteria, fungi, enteroviruses, herpes simplex virus 1 and 2, showed normal glycorrhachia albeit with 300 leukocytes/mm3 and slightly raised proteins (1.49 g/L). Blood was taken at the same time and the culture was sterile. Cerebral ultrasound and EEG were also normal. There were no signs suspected for metabolic diseases. Symptoms improved slowly over 3 days and a second CSF sample was normal on the fifth day of life, but mild hypotonia and feeding difficulty persisted. Main laboratory findings are resumed in Table 1. Magnetic resonance imaging at 11 days of life showed bilateral gliosis of the deep white periventricular and subcortical matter, with slightly left predominance (Fig. 2). The neonate did not receive antivirals or any other specific treatment, gradually recovered and was finally discharged from hospital after 18 days. Follow-up at almost 2 months of life showed a further improved neurological examination (improved hypertonia, normal motricity) and magnetic resonance imaging (reduced white matter injury); growth and rest of clinical exam were normal.

Table 1 Main laboratory findings in the neonate.
Fig. 2: Cerebral MRI performed at 11 days of life.
figure2

ab and cd T1 and diffusion-weighted sequences, respectively. Images are taken at two different levels and show hyperintensities of the periventricular and subcortical frontal or parietal white matter (arrows).

Virology and pathology

RT-PCR on the placenta was positive for both SARS-CoV-2 genes. Figure 3 shows all RT-PCR results obtained in different maternal and neonatal specimens: viral load was much higher in placental tissue, than in amniotic fluid and maternal or neonatal blood.

Fig. 3: Real-time polymerase chain reaction results.
figure3

ab The E and S genes of SARS-CoV-2, respectively, for maternal and neonatal samples (X and Y axes represent the amount of amplified RNA and the number of cycles, respectively; the earlier the signal is detected, the lowest is the number of cycles and the higher the viral load is). c The viral load for each sample (expressed as Log copies/million of cells for the placenta and as Log copies/mL for all other specimens). All maternal samples were obtained right before the delivery or during C-section; newborn samples are listed chronologically and were obtained from the first to the third day of life, except for the last nasopharyngeal swab (obtained at 18 days of postnatal age). Colored lines represent the results of RT-PCR assay for each sample. The deep orange line represents the positive control, which is a SARS-CoV-2 culture supernatant (more details in “Methods”). Nasopharyngeal swabs at 1, 3 and 18 day of life are represented by the light orange, gray and green curves, respectively. Viral load in BAL fluidis not shown. DOL days of life, M maternal samples, Nb newborn samples.

Placental histological examination was performed as described in “Methods” below and revealed diffuse peri-villous fibrin deposition with infarction and acute and chronic intervillositis. An intense cytoplasmic positivity of peri-villous trophoblastic cells was diffusely observed performing immunostaining with antibody against SARS-CoV-2 N-protein. No other pathogen agent was detected on special stains and immunohistochemistry. Figures 4 and 5 depict the results of the placental gross and microscopic examination, as well as immunohistochemistry.

Fig. 4: Gross and microscopic examination of the placenta.
figure4

a The macroscopic lesions of perivillous fibrin deposition with infarction, as irregular strands of pale yellow-white induration (arrow). b Microscopic lesions of intervillositis characterized by an infiltrate of the intervillous spaces made of neutrophils and histiocytes (arrow) (HES stain, original magnification ×400). c The intervillositis with several CD68-positive histiocytes (arrow); neutrophils are negative with this anti-macrophage antibody (anti-CD68 immunohistochemistry, original magnification ×400).

Fig. 5: Placental immunostaining for SARS-CoV-2 N-protein (anti-N immunohistochemistry, original magnification ×800).
figure5

a The intense brown cytoplasmic positivity of peri-villous trophoblastic cells in the placenta of our case (arrows). bc Two negative controls (primary antibody, two SARS-CoV-2 negative placentas).

Discussion

We report a proven case of transplacental transmission of SARS-CoV-2 from a pregnant woman affected by COVID-19 during late pregnancy to her offspring. Other cases of potential perinatal transmission have recently been described, but presented several unaddressed issues. For instance, some failed to detect SARS-CoV-2 in neonates or only reported the presence of specific antibodies1,2,4; others found the virus in the newborn samples but the transmission route was not clear as placenta, amniotic fluid and maternal or newborn blood were not systematically tested in every mother-infant pair3,5,6,11,12.

A classification for the case definition of SARS-CoV-2 infection in pregnant women, fetuses and neonates has recently been released and we suggest to follow it to characterize cases of potential perinatal SARS-CoV-2 transmission. According to this classification system, a neonatal congenital infection is considered proven if the virus is detected in the amniotic fluid collected prior to the rupture of membranes or in blood drawn early in life, so our case fully qualifies as congenitally transmitted SARS-CoV-2 infection, while the aforementioned cases would be classified as only possible or even unlikely13. Another recent report describes a case with similar placental findings, but it has been classified only as probable case of congenital SARS-CoV-2 infection, because cord and newborn blood could have not been tested14.

Both “E” and “S” gene of SARS-CoV-2 were found in each and every specimen, thus they were considered all positive, according to the European Centre for Disease Control recommendations (https://www.ecdc.europa.eu/en/all-topics-z/coronavirus/threats-and-outbreaks/covid-19/laboratory-support/questions). Of note, the viral load is much higher in the placental tissue than in amniotic fluid or maternal blood: this suggests the presence of the virus in placental cells, which is consistent with findings of inflammation seen at the histological examination. Finally, the RT-PCR curves of neonatal nasopharyngeal swabs at 3 and 18 day of life are higher than that at the first day (while the baby was in full isolation in a negative pressure room): this is also another confirmation that we observed an actual neonatal infection, rather than a contamination. Thus, these findings suggest that: (1) maternal viremia occurred and the virus reached the placenta as demonstrated by immunohistochemistry; (2) the virus is causing a significant inflammatory reaction as demonstrated by the very high viral load, the histological examination and the immunohistochemistry; (3) neonatal viremia occurred following placental infection. Our findings are also consistent with a case study describing the presence of virions in placental tissue, although this did not report neither placental inflammation, nor fetal/neonatal infection15.

The placenta showed signs of acute and chronic intervillous inflammation consistent with the severe systemic maternal inflammatory status triggered by SARS-CoV-2 infection. As RT-PCR on the placental tissue was positive for SARS-CoV-2, and both maternal and neonatal blood samples were also positive, the transmission clearly occurred through the placenta. Interestingly, placentas from women affected by SARS-CoV-1 presented similar pathological findings of intervillositis, with intervillous fibrin deposition16. Angiotensin-converting enzyme 2 (ACE2) is known to be the receptor of SARS-CoV-2 and is highly expressed in placental tissues17. Animal data show that ACE2 expression changes in fetal/neonatal tissues over time and reaches a peak between the end of gestation and the first days of postnatal life17. The combination of these data and our findings confirms that transplacental transmission is indeed possible in the last weeks of pregnancy, although we cannot exclude a possible transmission and fetal consequences earlier during the pregnancy, as there are no definite literature data available yet.

Interestingly, we described a case of congenital infection associated with neurological manifestations following neonatal viremia. Suspected neonatal SARS-CoV-2 infections presented with non-specific symptoms4 or pneumonia3, while neurological symptoms are commonly observed in adult patients, especially due to the inflammatory response18,19. Early neurological manifestations were also observed in another neonate born to SARS-CoV-2 positive mother, although vertical transmission was not fully investigated12. Conversely, after the viremia, our case clearly presented neurological symptoms and inflammatory findings in CSF. There was no other viral or bacterial infection and all other neonatal disorders potentially causing these clinical manifestations were excluded. Neuroimaging consistently indicated white matter injury, which can be caused by the vascular inflammation induced by SARS-CoV-2 infection, as similar images have been anecdotally found in adult patients20,21.

In conclusion, we have demonstrated that the transplacental transmission of SARS-CoV-2 infection is possible during the last weeks of pregnancy. Transplacental transmission may cause placental inflammation and neonatal viremia. Neurological symptoms due to cerebral vasculitis may also be associated.

Methods

Patient sampling

Biological samples to be tested by RT-PCR were obtained and prepared as follows. Nasopharyngeal and vaginal swabs were obtained following US Center for Disease Control and Prevention guidelines (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.htmlhttps://www.cdc.gov/groupbstrep/downloads/gbs_swab_sheet21.pdf). A sample of placental tissues was taken from the chorionic side and crushed in 400 mL of RNAase-DNAase-free water; 1 mL of blood and swabs were placed in Virocult® viral transport media (Sigma, St. Louis, MI, USA). Non-bronchoscopic bronchoalveolar lavage (BAL) was performed following a well-known standardized technique10: in detail, the neonate was placed supine with the head turned to the right so that the left lung would be predominantly sampled. Normal saline (1 mL/kg, 37 °C) was instilled into the endotracheal tube through a Y-piece. After three ventilator cycles, the suction catheter was gently inserted 0.5 cm beyond the tube tip, and the airway fluid was aspirated into a sterile specimen trap (BALF Trap; Vigon, Ecouen, France) with 50 mmHg of negative pressure. This procedure was repeated with the head turned to the left, so that the right lung would be predominantly sampled. This procedure respects European Respiratory Society advices for pediatric and neonatal BAL22. During the procedure, the patient was never disconnected from the ventilator, the inspired oxygen fraction was 0.25 and there was no desaturation or bradycardia. All specimens were kept at +4 °C and tested within 24 h.

Real-time polymerase chain reaction (RT-PCR)

Viral RNA was extracted from 200 µL clinical samples with the NucliSENS® easyMag® (BioMérieux, Craponne, France) and eluted in 100 µL. The RealStar® SARS-CoV-2 RT-PCR Kit 1.0 (Altona Diagnostics GmbH, Hamburg, Germany) targeting the E gene (specific for lineage B-betacoronavirus) and the S gene (specific for SARS-CoV-2) was used following the manufacturer’s recommendations (https://altona-diagnostics.com/en/products/reagents-140/reagents/realstar-real-time-pcr-reagents/realstar-sars-cov-2-rt-pcr-kit-ruo.html). The assay includes a heterologous amplification system (internal positive control) to identify possible RT-PCR inhibition and to confirm the integrity of the reagents of the kit. The positive control is a SARS-CoV-2 culture supernatant provided by the kit manufacturer. Thermal cycling was performed at 55 °C for 20 min for reverse transcription, followed by 95 °C for 2 min and then 45 cycles of 95 °C for 15 s, 55 °C for 45 s, 72 °C for 15 s with an Applied Biosystems ViiA7 instrument (Applied Biosystems, Thermo Fisher, Waltham, MA, USA). A cycle threshold value less than 40 is interpreted as positive for SARS-CoV-2 RNA. Our technique resulted to have an extremely low limit of detection (LOD = 1200 cp/mL (12 cp/rxn)). Reproducibility and inter-assay agreement were 100% both for negative and for positive tests, against two other common techniques23.

Placental examination

Placental sampling, gross and microscopic examination were performed according to the Amsterdam Consensus statement24. The placenta was fixed in 4% buffered formalin and samples were paraffin embedded. Staining methods performed on 3–5 µm thick sections were: haemalun eosin saffran, periodic acid schiff and Gomori-Grocott stains. Immunohistochemistry with peroxydase detection and hemalun counterstain was performed in a Leica Bond III automat using the Bond Polymer Refine Detection kit (Leica DS9800) after heat pretreatment at pH6 or 9 depending on the monoclonal antibodies tested: CD68 (Dako PG-M1, 1:200), CD163 (Leica 10D6, 1:200), CD20 (Dako L26, 1:400), CD3 (Dako F7.2.38, 1:50), CD5 (Novocastra 4C7, 1:50), CMV (Dako CCH2 + DDG9, 1:1), Parvo virus (AbcVs, Abc10-P038), SARS-CoV-2 (Abclonal, rabbit pAB, 2019-nCoV N Protein, 1:2400). Negative controls for SARS-CoV-2 immunohistochemistry were done: control of the polyclonal rabbit primary antibody, SARS-CoV-2 negative placental specimen with similar pre-analytic conditions of formalin fixation.

Ethics declaration

Written informed consent was obtained from the woman for the publication of this report. According to French regulation, institutional review board (IRB) approval is not required for case reports, provided that patients’ written consent is obtained. The French Ethical Committee for the Research in Obstetrics and Gynecology reviewed the work and confirmed that the IRB approval was unnecessary. The case study was performed in agreement with principles of the Declaration of Helsinki and CARE guidelines25.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability

All data generated or analyzed during this study are included in this published article.

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Transplacental transmission of SARS-CoV-2 infection
Author: Alexandre J. Vivanti et al
Publication: Nature Communications
Publisher: Springer Nature
Date: Jul 14, 2020

Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain

Publicado originalmente no JAMA Network. Acesse o original (em inglês)
JAMA. Published online June 8, 2020. doi:10.1001/jama.2020.10125
Data from China found severe complications in 8% of pregnant women with coronavirus disease 2019 (COVID-19).1 However, the high rate of cesarean deliveries (>90%) in Chinese reports is concerning,2 and whether mode of delivery is associated with maternal complications or neonatal transmission is unknown.3 We assessed births to women with COVID-19 by mode of delivery.

Gravidez, nascimento e a pandemia de COVID-19 nos Estados Unidos

Acesse o original (em inglês)

Pregnancy, Birth and the COVID-19 Pandemic in the United States

Published online: 14 May 2020

How quickly and in what ways are US maternity care practices changing due to the COVID-19 pandemic? Our data indicate that partners and doulas are being excluded from birthing rooms leaving mothers unsupported, while providers face lack of protective equipment and unclear guidelines. We investigate rapidly shifting protocols for in- and out-of-hospital births and the decision making behind them. We ask, will COVID-19 cause women, families, and providers to look at birthing in a different light? And will this pandemic offer a testing ground for future policy changes to generate effective maternity care amidst pandemics and other types of disasters?

Coronavírus: grávidas e puérperas na pandemia

Grávidas e puérperas são grupo de risco 
Leia a Matéria Original

Muitos questionamentos e emoções envolvem a chegada de uma nova vida. Do descobrimento da gravidez até o momento do parto, as incertezas e a insegurança mexem com a cabeça de mães e pais. O período após o nascimento do bebê também não é diferente. Nos últimos meses, uma nova preocupação entrou na lista: o coronavírus.

Em nota à imprensa, o Ministério da Saúde informou sobre uma mudança de protocolo que inclui grávidas e puérperas no grupo de risco para a COVID-19. Esse novo status exige maior atenção nos cuidados individuais e coletivos, já que essas mulheres podem apresentar casos mais graves da doença. Marcus Renato de Carvalho, professor da Faculdade de Medicina da UFRJ e pediatra, afirma que o momento deve ser de observação e cuidados. “É importante que elas tomem ainda mais precauções para se proteger e relatem possíveis sintomas para seus provedores de cuidados de saúde”, disse, completando que o distanciamento também é uma das formas de proteção para as gestantes.

Estas são algumas das indicações para esse público: trabalho remoto ou  afastamento, principalmente para trabalhadoras da saúde; apenas consultas e exames essenciais do pré-natal, com utilização da teleconsulta sempre que possível; ausência de visitas durante a gestação e o pós-parto; atenção redobrada à higiene dos cuidadores da mulher e do bebê.

O momento do parto também exige cuidados redobrados. Procedimentos dispensáveis, como cesáreas eletivas e indução desnecessária, devem ser evitados para que a parturiente não precise ficar mais tempo no hospital. Carvalho afirma que é preciso avaliar a presença do acompanhante, que não deve apresentar sintomas nem ser dos grupos de risco, minimizando assim as chances de infecção. “Mas isso não quer dizer que a presença do acompanhante deve ser negada”, ressalta.

Aleitamento é necessário

Não há nenhuma evidência científica que aponte o leite materno como uma possível fonte de transmissão da doença. O professor reitera que a orientação do MS é de que a amamentação não deve ser suspensa em casos de a mãe ter a suspeita de infecção pelo novo coronavírus, mas que é preciso seguir um protocolo de cuidados mais rígido. O uso de máscara é indispensável nesses casos, assim como a higienização das mãos antes e depois do aleitamento.

“Salvo alguma intercorrência que exija a separação do binômio, como, por exemplo, o agravamento das condições de saúde maternas, é perfeitamente possível que mãe e filho permaneçam em sistema de alojamento conjunto na maternidade até a alta hospitalar”, explica.

Isolamento não é abandono

Um dos momentos mais delicados para uma nova família é o puerpério. Conhecido como “blues puerperal”, o período que se segue ao parto é, muitas vezes, solitário. Segundo Carvalho, alguns casos podem ser o início de um quadro de depressão pós-parto. “O apoio da família e a participação do companheiro ou companheira são essenciais para que a mulher sinta-se segura nesse momento”.

A rede de apoio, essencial nessa fase, precisa continuar dando suporte à nova família, e as novas tecnologias podem ajudar, seja por vídeo, ligações ou mensagens. “E, também, não deve ser abandonada pelo obstetra, pediatra, enfermeira obstetra, doula, psicóloga ou alguém da equipe perinatal com quem ela tenha feito uma melhor conexão ou vínculo afetivo”, declara.

O professor lembra também que, mais do que nunca, os pais precisam assumir seus papéis na criação dos filhos, valendo-se de suas licenças-paternidades e antecipação de férias para dividirem as tarefas de maneira justa, cuidando dos afazeres domésticos, do bebê e, claro, da mãe.