Authors: Nerea Maiz1,2, Berta Serrano1, Anna Suy1, Elena Carreras1,2
1 Hospital Universitari Vall d’hebron. Barcelona. Catalonia. Spain.
2 Universitat de Vic-Universitat central de Catalunya. Catalonia. Spain.
The infection caused by the SARS-CoV-2 virus, which causes the COVID-19 disease, was first described in the city of Wuhan, China, in December 2019 and rapidly spread to the rest of the planet. The World Health Organization declared the coronavirus infection a pandemic in March 2020. A progressive accumulation of scientific evidence since the beginning of the pandemic has tried to determine the effect of this new disease on pregnancy and the influence of pregnancy in the course of the disease.
Pregnant women have higher risk of disease and mortality due to certain respiratory infections. Normal changes of pregnancy make these patients especially susceptible to respiratory infections.
Respiratory changes during pregnancy include increasing oedema and congestion in the upper airway tract and elevation of the diaphragm. These changes cause increased susceptibility to respiratory pathogens, added to others such as immunotolerance, metabolic changes, etc., make pregnancy a situation of special susceptibility.
The incubation period of SARS-CoV-2 goes usually from 5 to 6 days but can range from 1 to 14 days. The most likely moment to transmit the infection is just before the onset of symptoms. The virus can be transmitted even in asymptomatic patients, although the patients with severe disease can be contagious for longer time.
The spread of the virus occurs through small liquid particles of different sizes (ranging from droplets to aerosols) expelled by an infected person by coughing, sneezing, talking or breathing. Transmission occurs mainly with close contacts (<1 meter), although it can also occur with the suspension of aerosols or due to surface contamination.
Similar to non-pregnant patients, the main signs and symptoms of pregnant women with COVID-19 are cough (41%), fever (40%), dyspnea (21%), myalgia (19%), loss of taste and smell (14 %) and diarrhea (8%). Compared with non-pregnant patients of the same age, pregnant women are less symptomatic. It can be difficult to distinguish between dyspnea caused by infection and physiological dyspnea due to increased oxygen caused by an increased basal metabolism, gestational anemia and fetal oxygen consumption.
The most remarkable laboratory abnormalities are elevated C-reactive protein (CRP) (49%), lymphopenia (33%), leukocytosis (26%), transaminitis (13%) and thrombocytopenia (6%).
The most prevalent chest radiograph abnormalities are unilateral or bilateral opacities and bilateral pneumonia.
The incidence of SARS-CoV-2 infection in pregnant women is around 10%, with a higher risk in non-white pregnant women. Around 75% are asymptomatic and is proportionally higher in the first quarter than in the third.
Symptoms are usually mild, around 10% require admission to the ICU and around 5% require mechanical ventilation.
Although the most infected pregnant women recover without requiring hospitalization, symptomatic patients have higher risk of severe disease and complications than non-pregnant population.
Compared with non-pregnant women of the same age, pregnant women with COVID-19 have a higher risk of admission to ICU, need for ventilation mechanical, need for extracorporeal membrane oxygenation (ECMO) and death.
Risk factors associated with severe COVID-19 in pregnancy are age, high body mass index (BMI), chronic hypertension, preeclampsia) and diabetes.
Risk factors associated with need for mechanical ventilation or death are non-white ethnicity and high BMI .
Diagnostic techniques in pregnant women are similar to those of the general population.
Clinical suspicion is the first tool for the diagnosis of COVID-19. In pregnant women, the infection should be ruled out in the event of a close contact with an infected person as well as in the presence of fever or respiratory symptoms in a previously asymptomatic patient. In most health-care centers, a SARS-CoV-2 screening is also performed at the time of admission of any pregnant woman.
There are several techniques available for the diagnosis of SARS-CoV-2 infection, being the gold standard in pregnant women the reverse transcriptase-polymerase chain reaction (RT-PCR). Its specificity is very high and its sensitivity, which is close to 70%, can vary depending on the presence of symptoms, the technique or the time of collection of the sample. A positive test confirms the diagnosis and a negative test must be individualized: if the patient has symptoms suggestive of COVID-19, it is advisable to repeat the test.
If there is no availability of RT-PCR, a reasonable alternative is to use an antigen test, especially if the patient is symptomatic. The results of this test are faster than RT-PCR, although sensibility lowers.
Serology allows the identification of patients who have previously had a SARS-CoV-2 infection. Antibodies can be detected several days after the onset of infection. Usually, 16 to 20 days after the onset of symptoms the vast majority of patients will present detectable IgG in the blood test. Thus, serology is not a good screening test for COVID-19 infection, but it is useful to confirm and monitor patients.
All pregnant women admitted at the time of delivery are screened for SARS-CoV-2. If it is a planned delivery, an induction of labour or an elective cesarean section, the test is performed 24-72 hours before the procedure. If the screening is positive, it allows planning and assessing the severity of the symptoms.
Ensuring that the patient can go through labour and delivery accompanied by whomever she chooses must be a priority. Nevertheless, usually only one support person is allowed to minimize the risk of infection. The support person is allowed throughout admission, labour, birth and post-partum, following the same isolation procedures than the pregnant woman.
In asymptomatic patients or patients with mild to moderate disease, delivery must be decided due to obstetric causes and procedures such as the induction technique or the use of epidural anaesthesia should not differ from the usual ones. In patients with severe or critical illness, delivery must be individualized based on clinical severity and gestational age.
During the immediate post-partum skin-to-skin and breastfeeding are encouraged.
Pregnant women with severe COVID-19 can develop a condition similar to severe preeclampsia, with hypertension, proteinuria, and elevated liver enzymes, described as preeclampsia-like syndrome.
Positive pregnant women have a higher risk of preterm delivery, being 83% by medical indication, mostly due to pre-eclampsia, intrauterine growth retardation or fetal distress. The increased risk of preterm delivery appears to be higher in patients with severe disease.
No differences were observed regarding the way of delivery, with a caesarean section rate of 37.5%.
Newborns of affected mothers have a higher risk of admission to the Neonatal ICU (33%,), although hospital policies for the observation of these babies may have influenced this result.
Vertical transmission is defined as the pass of the pathogen from the mother to the neonate during pregnancy (congenital transmission), childbirth (perinatal transmission) or postpartum (neonatal transmission), through the placenta, the uterus or the contact of fluids in childbirth or breastfeeding.
Although there are a few well-documented cases of vertical transmission, the available data suggest that the risk of congenital transmission is low.
Risk of transmission from infected mothers to the neonate is defined as a positive neonatal SARS-CoV-2 test immediately after delivery up to 48 hours of life and it is 3.2%. Positive samples for SARS-CoV-2 have been found in cord blood (2.9%), placenta (7.7%), fecal or rectal smears (9.7%) and positive IgM serologies (3.7%).
Although some studies have reported an increased risk of stillbirth in the second trimester compared to non-COVID-19 patients, it has not been possible to demonstrate a significant increase in its incidence. It is interesting to note that relevant alterations were found in stillbirth placentas in positive pregnant women.
Some cases of subcutaneous fetal edema have also been described in patients with COVID-19 that resolved spontaneously after the mother’s SARS-CoV-2 RT-PCR was negative.
Vertical transmission of SARS-CoV-2 is possible although it appears to occur rarely. Some newborns born to COVID-19 mothers have developed signs of mild infection, but in most cases, it has been attributed to postnatal transmission.
The treatment of COVID-19 has varied over time as scientific evidence has been generated in this regard.
Pregnancy involves increased thrombin generation, a prothrombotic state and increased intravascular inflammation. COVID-19 infection increases the incidence of venous and arterial thromboembolism. Therefore, the use of low molecular weight heparin (LMWH) at prophylactic doses is widely accepted in all COVID-19 pregnant women.
Dexamethasone 6mg / 24h (oral or intravenous) is recommended for 10 days in patients who require oxygen therapy. On the other hand, the use of methylprednisolone has been shown to improve the prognosis of adult respiratory distress syndrome (ARDS).
Among corticosteroids, dexamethasone and betamethasone are the only two recommended for accelerating fetal lung maturation on preterm birth, since they have the highest rate of placental transfer. The other corticosteroids are not as good because they are metabolized in the placenta and their placental passage is reduced. Nevertheless, corticosteroids during pregnancy can been associated with neonatal neurological alterations, decreased head circumference, intrauterine growth restriction and risk of neonatal hypoglycemia.
Tocilizumab is an accepted monoclonal antibody for the treatment of COVID-19 pneumonia with ≥7 days of clinical evolution and associated corticosteroid treatment. In pregnant women its administration will require an individualized assessment.
Remdesivir is an accepted antiviral for the treatment of COVID-19 pneumonia with oxygen therapy without need for mechanical ventilation. In pregnant women it is approved as compassionate use.
Respiratory rehabilitation uses a series of techniques, exercises, education and postural and habit changes designed to improve the physical condition of COVID-19 pregnant women. It aims to improve dyspnea, reduce anxiety, reduce complications, minimize sequelae and preserve lung function and quality of life.
During the acute management of the COVID-19 pregnant woman, use of respiratory rehabilitation should be considered whenever is feasible, since it contributes to her clinical improvement. Patients without severe disease or who do not require admission could also benefit from the advantages of these techniques.
Regarding preventive measures, pregnant women should follow the same recommendations as the general population to avoid exposure to the virus, including the safety distance, use of a mask and hand washing. In positive patients, home isolation is recommended until symptomatic improvement and COVID teste are negative. If the patient is positive during delivery, preventive and isolation measures will be applied for her and her support person as well as health personnel involved. During the immediate post-partum skin-to-skin and breastfeeding are encouraged.
Many vaccines have been evaluated for the prevention of COVID-19, but pregnant women have been initially excluded in all clinical trials. Randomized studies are currently evaluating the efficacy and safety of vaccines against SARS-CoV-2 in pregnant women. An observational study analyzing the use of the Pfizer BNT162b2 vaccine in pregnant women has not reported significant rates of gestational complications but has detected significantly lower IgG concentrations than in nonpregnant women.
Animal studies and available vaccination data in pregnant women to date suggest that the vaccine is safe in pregnancy, but the information is still limited. Knowing it, if the patient decides to be vaccinated, it is advisable to seek advice from her health professional of reference. The usefulness of the vaccine in pregnant women is still uncertain but promising.
The Foundation for the Development of Internal Medicine (FDIME),
Daniel Sereni, Ramon Pujol, Jan Willem Elte.
Corrector English language: Chris Davidson
With the help of Imad Hatem, Nica Cappellini, Lorenzo Dagna, Runolfur Palsson, Stefan Lindgren, Vereny Briner, Werner Bauer (in random order).