Covid-19 in pregnancy.....what should I know?
If you haven't heard by now, there a pandemic running around everywhere. I have received a lot of calls from a local high end Emergency Services center and realize a lot of pregnant women that may be at risk are presenting for testing and some are even testing positive. Having come from serving in San Antonio with several hopsital systems I have seen first hand what can happen and its consequences. The knowledge we as a medical community has drastically evolved including the emergence of 2-3 viable vaccinations. That's not saying this is the end all of information as this can still change and adapt as new information becomes available but hopefully this will help allay a lot of fears and provide more reliable data to make better decisions not just for patients but also practitioners.
First off, always start with a good foundation of what the problem is. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). I will try to broach this topic as it relates solely to SARS-CoV-2 and COVID-19 in pregnant persons during the prenatal period. Labor, delivery, and postpartum issues will be discussed separately.
Pregnant and nonpregnant persons from racial and ethnic minority groups have higher rates of COVID-19, associated hospitalizations, and severe in-hospital outcomes, which may be related to differences in social determinants of health. This mean women of color that are in this instance at a disadvantage when it comes to outcomes.
In pregnancy, vertical transmission particularly is a concern (the virus crosses the placenta and infects an unborn fetus) but this is a rare finding. Pregnant persons should follow the same recommendations as non-pregnant persons for avoiding exposure to the virus if community transmission is present (eg, physical distancing [at least six feet (two meters)], wearing a two- or three-layer face covering when proximate to anyone not living in your household, avoiding indoor crowded spaces [eg, bars and restaurants] and outdoor crowds, washing or sanitizing hands frequently, disinfecting frequently touched surfaces). In particular, they should avoid close contact with ill individuals. Those with contact with a confirmed or suspected case of COVID-19 should be monitored.
Pregnant mothers with children in the household should exercise caution. COVID-19 in children under 10 years of age is often mild and may be asymptomatic, although severe cases have been reported. Given the possibility of transmission of SARS-CoV-2 from asymptomatic individuals (or presymptomatic individuals within the incubation period), the Centers for Disease Control and Prevention (CDC) recommends limiting in-person playtime with children from other households and advises parents to take measures to protect their children when they play with children from other households (eg, connect virtually if possible, play outside, wear cloth face coverings) [
A number of professional organizations provide information regarding school reopening but I will not delve into this topic in this article, since this has also become politicized. Pregnant non-health care and health care workers using appropriate personal protective equipment should be able to continue to work until they deliver, but risk mitigation, such as reassignment at term to roles with reduced risk of exposure or self-quarantine, is reasonable. The patient's comorbidities and individual work situation should guide the clinician's response to requests for medical leave. There is no standard occupational guidance for pregnant health care workers regarding work restrictions.
What is COVID-19?COVID-19 stands for "coronavirus disease 2019." It is caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and quickly spread around the world.People with COVID-19 can have fever, cough, trouble breathing, and other symptoms. Problems with breathing happen when the infection affects the lungs and causes pneumonia.Most people who get COVID-19 will not get severely ill. But some do. In many areas, people have been told to stay home and away from other people. This is to try to slow the spread of the virus.This article has information for people who are pregnant. More general information about COVID-19 is available separately.
How is COVID-19 usually spread?The virus that causes COVID-19 mainly spreads from person to person. This usually happens when an infected person coughs, sneezes, or talks near other people. The virus is passed through tiny particles from the infected person's lungs and airway. These particles can easily travel through the air to other people who are nearby. In some cases, like in indoor spaces where the same air keeps being blown around, virus in the particles might be able to spread to other people who are farther away.The virus can be passed easily between people who live together. But it can also spread at gatherings where people are talking close together, shaking hands, hugging, sharing food, or even singing together. Eating at restaurants raises the risk of infection, since people tend to be close to each other and not covering their faces. Doctors also think it is possible to get infected if you touch a surface that has the virus on it and then touch your mouth, nose, or eyes.A person can be infected, and spread the virus to others, even without having any symptoms. This is why keeping people apart is one of the best ways to slow the spread.What are the symptoms of COVID-19?Symptoms usually start 4 or 5 days after a person is infected with the virus. But in some people, it can take up to 2 weeks for symptoms to appear. Many people never show symptoms at all.When symptoms do happen, they can include:
●Fever
●Cough
●Trouble breathing
●Feeling tired
●Shaking chills
●Muscle aches
●Headache
●Sore throat
●Problems with sense of smell or taste
Some people have digestive problems like nausea or diarrhea.Pregnant people with COVID-19 can have any of the above symptoms or no symptoms.For most people, symptoms will get better within a few weeks. But in others, COVID-19 can lead to serious problems like pneumonia, not getting enough oxygen, heart problems, or even death. This risk gets higher as people get older. It is also higher in people who have other health problems like serious heart disease, chronic kidney disease, type 2 diabetes, chronic obstructive pulmonary disease (COPD), sickle cell disease, or obesity. People who have a weak immune system for other reasons (for example, HIV infection or certain medicines), asthma, cystic fibrosis, type 1 diabetes, or high blood pressure might also be at higher risk for serious problems.Are pregnant people at high risk for severe symptoms?Experts do not yet know a lot about COVID-19 and pregnancy. From what they know so far, pregnant people do not seem more likely than other people to get the infection.However, compared with women of the same age who are not pregnant, pregnant people with COVID-19 seem to be more likely to get very sick and need to stay in the ICU. ("ICU" is short for "intensive care unit.") In pregnant people, the risk of getting very sick is highest in those who are age 35 or older, obese, or have high blood pressure or diabetes. But most people recover before having their baby, and do not need to stay in the hospital. Pregnant people are not at higher risk of dying from COVID-19 than other people of similar age.What should I do if I have symptoms?If you have a fever, cough, trouble breathing, or other symptoms of COVID-19, call your doctor, nurse, or midwife. They can tell you what to do and whether you need to be seen in person. They will also tell you if you should be tested for the virus that causes COVID-19.If I am pregnant and get infected, can I pass the virus to my baby?Experts think it might be possible for a baby to get the infection while still in the uterus. But this seems to be very uncommon. And when it does happen, most babies do not get very sick.It is also possible to pass the virus to the baby during childbirth or after the baby is born. If you have COVID-19 when you give birth, there are ways to lower this risk.Can COVID-19 cause problems with pregnancy?From what experts know so far, most people who get COVID-19 during pregnancy will not have serious problems. But problems can happen if the mother becomes seriously ill.Pregnant people who get COVID-19 might have an increased risk of preterm birth. This is when the baby is born before 37 weeks of pregnancy. This seems to be more of a risk in people who get very sick and have pneumonia. Preterm birth can be dangerous, because babies who are born too early can have serious health problems.How is COVID-19 treated?Most people with mild illness will be able to stay home while they get better. Mild illness means you might have symptoms like fever and cough, but you do not have trouble breathing.People with serious symptoms or other health problems might need to go to the hospital. If you need to be treated in the hospital, the doctors and nurses will also monitor your baby's health.Doctors are studying several possible treatments for COVID-19. In certain cases, doctors might recommend medicines that seem to help some people who are severely ill. They also might recommend being part of a clinical trial. A clinical trial is a scientific study that tests new medicines to see how well they work. But some medicines are not safe to take if you are pregnant.Fever is a common symptom of COVID-19. If you are pregnant and get a fever, ask your doctor, nurse, or midwife what to do. Acetaminophen (sample brand name: Tylenol) can be used to treat a fever and is generally safe to take during pregnancy.Can COVID-19 be prevented?Experts are working on vaccines to prevent COVID-19. When a vaccine becomes widely available, if a lot of people get it, the virus will stop spreading so quickly.While we wait for a vaccine, there are other things you can do to reduce your chances of getting COVID-19. In general, it's a good idea to be extra careful about hand washing and avoiding sick people when you are pregnant.To help slow the spread of COVID-19:
●Practice "social distancing." This means keeping people, even those who are healthy, away from each other. It is also sometimes called "physical distancing." The goal is to slow the spread of the virus that causes COVID-19.Avoiding large groups and events is an important part of social distancing. But even small gatherings can be risky, so it's best to stay home as much as you can. When you do need to go out, try your best to stay at least 6 feet (about 2 meters) away from other people.
●Wear a face mask when you need to go out. Experts in many countries recommend doing this. It is mostly so that if you are infected, even if you don't have any symptoms, you are less likely to spread the infection to other people. It might also help protect you from others who could be infected. Make sure your mask covers your mouth and nose.You can buy cloth masks and disposable (non-medical) masks in stores or online. Cloth masks work best if they have several layers of fabric. When you take your mask off, make sure you do not touch your eyes, nose, or mouth. And wash your hands after you touch the mask. You can wash cloth masks with the rest of your laundry.
●Wash your hands with soap and water often. This is especially important after being out in public. Make sure to rub your hands with soap for at least 20 seconds, cleaning your wrists, fingernails, and in between your fingers. Then rinse your hands and dry them with a paper towel you can throw away. Hand washing also helps protect you from other illnesses, like the flu or the common cold.If you are not near a sink, you can use a hand sanitizing gel to clean your hands. The gels with at least 60 percent alcohol work the best. But it is better to wash with soap and water if you can.
●Avoid touching your face with your hands, especially your mouth, nose, or eyes.
●Avoid traveling if you can. Some experts recommend not traveling to or from certain areas where there are a lot of cases of COVID-19. But any form of travel, especially if you spend time in crowded places like airports, increases your risk. If lots of people travel, it also makes it more likely that the virus will spread to more parts of the world.Will my regular prenatal appointments change?Your doctor, nurse, or midwife will work with you to make a plan for your visits during pregnancy.
If you live in an area where there are a lot of cases of COVID-19, there will likely be some changes. For example:
●Your partner might not be able to join you for appointments
●If you have any symptoms of COVID-19, you will probably need to wear a medical mask during your appointments
●Your doctor, nurse, or midwife might group certain tests together so you don't need to go in as often
●Your doctor, nurse, or midwife might suggest replacing some visits with a phone or video call
These changes can feel stressful. It can help to keep in mind that the goal is to help protect you and others.What will my delivery be like?You will be checked for fever and other symptoms of COVID-19 when you get to the hospital or birth center. This might happen earlier if you are scheduled to be "induced" or have a cesarean delivery ("c-section"). You might be tested for the virus, too. Even if you feel healthy, you should cover your nose and mouth with a mask before going to the hospital. You can also expect to wear a mask during labor and delivery.If you have COVID-19 when you go into labor, the doctors and nurses will take steps to protect others around you. For example, you will need to wear a medical mask if possible. You will probably still be able to have a vaginal birth, if that is what you planned. You don't need a c-section just because you are sick.If you have COVID-19, your doctor or nurse might suggest staying apart from your baby until you get better. This will depend on how sick you are, whether your baby has been tested for the virus, and other factors. If you do hold your baby, you will need to wear a face mask to lower the risk of spreading the infection. You might need to take other precautions, too. These things can be hard. But they are important in order to protect your baby.If we are both healthy, can my partner be with me for the birth?In areas with a lot of cases of COVID-19, some hospitals have rules about who can be in the room during labor and delivery. Your doctor, nurse, or midwife can talk to you about what to expect. Your partner will not be allowed to be there if they have symptoms of COVID-19, have tested positive for the virus, or might have been exposed to someone who has it. If your partner cannot be with you, there is usually a way to have them support you over the phone or by video.Some people wonder if it would be safer to give birth at home instead of at the hospital. If you are curious about this, talk to your doctor, nurse, or midwife. Home birth has risks, too.What if I want to breastfeed?Breastfeeding has many benefits for both you and your baby. It is not known if the virus that causes COVID-19 can be passed to a baby through breast milk.If you are sick, you might want to have another healthy adult feed your baby. If that is not possible, it's important to be extra careful when feeding or holding your baby, whether or not you breastfeed. Even though experts do not know if the virus can be spread through breast milk, you could pass it to your baby through close contact. You can protect your baby by washing your hands often and wearing a face mask while you feed them.You might choose to pump breast milk for your baby. If you are sick, wash your hands carefully before pumping, and wear a mask while you pump. If possible, have a healthy person clean your pump thoroughly between uses.
What can I do to cope with stress and anxiety?It's normal to feel anxious or worried about COVID-19. If you are pregnant, you might feel sad about having to cancel celebrations and stay away from relatives and friends.You can take care of yourself by trying to:
●Take breaks from the news
●Get regular exercise and eat healthy foods
●Try to find activities that you enjoy and can do in your home
●Stay in touch with your friends and family members
Keep in mind that most people do not get severely ill from COVID-19. It helps to be prepared, and it's important to do what you can to lower your risk and help slow the spread of the virus. But try not to panic.What if I have other questions?If you have other questions, talk to your doctor, nurse, or midwife. They can help you with questions like:
●What symptoms should I be concerned about?
●What should I do if I think I was exposed to COVID-19?
●What medicines can I use to treat symptoms of COVID-19 while I am pregnant?
●Where can I find support if I feel anxious or depressed?The answers to these questions, and others, will depend on your situation.Where can I go to learn more?
As we learn more about this virus, expert recommendations will continue to change. Check with your doctor or public health official to get the most updated information about how to protect yourself and your family.For information about COVID-19 in your area, you can call your local public health office. In the United States, this usually means your city or town's Board of Health. Many states also have a "hotline" phone number you can call.You can find more information about COVID-19 at the following websites:
●United States Centers for Disease Control and Prevention (CDC): www.cdc.gov/COVID19
●World Health Organization (WHO): www.who.int/emergencies/diseases/novel-coronavirus-2019
Vaccines — Numerous vaccines are being evaluated for prevention of COVID-19, but pregnant women have been excluded from these trials. The first vaccines from Pfizer and Moderna likely to become clinically available are based on mRNA and do not contain infectious virus (either SARS-CoV-2 or a vector virus). I recommend not withholding the SARS-CoV-2 vaccine on the basis of pregnancy alone for those who are eligible for and desire it but will need to wait for guidance from the CDC and the American College of Obstetrics and Gynecology. Counseling should balance available data on vaccine safety, risks to pregnant patients from SARS-CoV-2 infection, and the patient's individual risk for infection and severe disease. Fetal effects of the vaccine are unknown, while it is known that pregnant women who become infected with COVID-19 are at increased risk of severe maternal disease and adverse pregnancy outcome. As data emerge, some vaccines may be more suitable for pregnant women and others less suitable (vaccines contain infectious virus [eg, adenoviral vector vaccines]).
All pregnant persons should be monitored for development of symptoms and signs of COVID-19 (which are similar to those in nonpregnant individuals particularly if they have had close contact with a confirmed case or persons under investigation. In a report from the Centers for Disease Control and Prevention (CDC) COVID-19 Response Pregnancy and Infant Linked Outcomes Team that included over 23,000 pregnant persons and over 386,000 non-pregnant females of reproductive age with symptomatic laboratory-confirmed SARS-CoV-2 infection, the frequency of the most common symptoms in each group was
:●Cough: 50.3 percent (51.3 percent in nonpregnant females)
●Headache: 42.7 percent (54.9 percent in nonpregnant females)
●Muscle aches: 36.7 percent (45.2 percent in nonpregnant females)
●Fever: 32.0 percent (39.3 percent in nonpregnant females)
●Sore throat: 28.4 percent (34.6 percent in nonpregnant females)
●Shortness of breath: 25.9 percent (24.8 percent in nonpregnant females)
●New loss of taste or smell: 21.5 percent (24.8 percent in nonpregnant females)
Other symptoms that occurred in >10 percent of each group included nausea or vomiting, fatigue, diarrhea, and rhinorrhea (runny nose).Many pregnant persons are asymptomatic, but the proportion of asymptomatic cases is not well defined. In a systematic review, 7 percent of pregnant persons universally screened for COVID-19 tested positive, and 75 percent of these persons were asymptomatic. In another systematic review, 95 percent (95% CI 45-100 percent) of COVID-19 infections in pregnant persons were asymptomatic and 59 percent (95% CI 49-68 percent) remained asymptomatic through follow-up.
The hard part for some clinicians is that the clinical manifestations of COVID-19 overlap with symptoms of normal pregnancy (eg, fatigue, shortness of breath, nasal congestion, nausea/vomiting), which should be considered during evaluation of afebrile women.
Chest X-rays may be normal in early or mild disease. Laboratory findings in a systematic review of pregnant and recently pregnant persons with suspected or confirmed COVID-19 including the following findings:
●Leukocytosis (27 percent)
●Elevated procalcitonin level (21 percent)
●Abnormal liver chemistries (11 percent)
●Thrombocytopenia (8 percent)
Laboratory and imaging findings are similar to those in nonpregnant persons. However, leukocytosis (elevated white blood cell count) can be normal in pregnancy and some of the other laboratory findings overlap with those caused by pregnancy-related disorders (eg, thrombocytopenia (low platelet counts) and elevated liver chemistries in preeclampsia with severe features).
Classification of disease severity — In the United States, the National Institutes of Health (NIH) have categorized degrees of disease severity in nonpregnant persons as follows:
●Asymptomatic or presymptomatic infection – Positive test for SARS-CoV-2 but no symptoms.
●Mild illness – Any signs and symptoms (eg, fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnea, or abnormal chest imaging.
●Moderate illness – Evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SaO2) ≥94 percent on room air at sea level.
●Severe illness – Respiratory frequency >30 breaths per minute, SaO2 <94 percent 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 percent.
●Critical illness – Respiratory failure, septic shock, and/or multiple organ dysfunction.
A separate categorization may also be used called the Wu classification]:
●Mild – No or mild symptoms (fever, fatigue, cough, and/or less common features of COVID-19).
●Severe – Tachypnea (respiratory rate >30 breaths per minute), hypoxia (oxygen saturation ≤93 percent on room air or PaO2/FiO2 <300 mmHg), or >50 percent lung involvement on imaging).
●Critical (eg, with respiratory failure, shock, or multiorgan dysfunction).Other definitions of severity exist (eg, severe = maternal peripheral oxygen saturation [SpO2] ≤94 percent on room air, requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]) and are discussed separately.
Pregnancy and childbirth generally do not increase the risk for acquiring SARS-CoV-2 infection but appear to worsen the clinical course of COVID-19 compared with nonpregnant individuals of the same sex and age. Clinical deterioration may be rapid. In the United States, it is estimated that 1 to 3 percent of pregnant patients with COVID-19 have been admitted to an intensive care unit; incomplete data limit the accuracy of the estimate. However, most (>90 percent) infected persons recover without undergoing hospitalization or delivery.
Complications of COVID-19 include, but are not limited to:
●Respiratory disorders: pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS)
●Cardiac disorders (arrhythmias, acute cardiac injury)
●Thromboembolic complications
●Secondary infections
●Acute kidney failure
●Neurologic disorders: headache, dizziness, myalgia, alteration of consciousness, disorders of smell and taste, weakness, strokes, seizures
●Cutaneous disorders: morbilliform rash; urticaria; pernio-like, acral lesions; livedo-like, vascular lesions; and vesicular, varicella-like eruption
●Gastrointestinal and liver disorders
It is known that some patients with severe COVID-19 have laboratory evidence of an exuberant inflammatory response (similar to cytokine release syndrome), which has been associated with critical and fatal illnesses. Whether the normal immunologic changes of pregnancy affect the occurrence and course of this response is unknown. The following examples show the spectrum of the clinical course of COVID-19 in pregnant persons in three large datasets:
●In a systematic review including over 11,000 pregnant and recently pregnant women with suspected or confirmed COVID-19:
•49 percent had pneumonia
•30 percent received oxygen by cannula
•13 percent had severe disease
•4 percent were admitted to an intensive care unit (ICU)
•3 percent received invasive ventilation
•0.8 percent received extracorporeal membrane oxygenation (ECMO)
•0.6 percent died
Pregnant women were more likely to need ICU admission compared with nonpregnant women of reproductive age with COVID-19 (odds ratio [OR] 1.62) and pregnant women without COVID-19 (OR 72). Risk factors associated with severe disease or ICU admission included age ≥35 years, obesity, hypertension, and preexisting diabetes.However, these findings have many limitations. For example, the primary studies included women with both suspected and confirmed infection; largely consisted of pregnant women who required visits to the hospital, such as for childbirth, thus affecting the generalizability of the estimates; often did not indicate timing of assessment of the clinical manifestations of disease; used different definitions of symptoms, tests, and outcomes; generally did not provide adequate information to distinguish iatrogenic effects from the true impact of the disease; and the findings for some outcomes were based on one or two studies.
●In a report from the Centers for Disease Control and Prevention (CDC) COVID-19 Response Pregnancy and Infant Linked Outcomes Team that included over 23,000 pregnant persons and over 386,000 nonpregnant females of reproductive age with symptomatic laboratory-confirmed SARS-CoV-2 infection, pregnant patients had a higher risk of]:
•ICU admission (10.5 versus 3.9 per 1000 cases, adjusted risk ratio [aRR] 3.0, 95% CI 2.6-3.4)
•Receiving invasive ventilation (2.9 versus 1.1 per 1000 cases, aRR 2.9, 95% CI 2.2-3.8)
•Receiving ECMO (0.7 versus 0.3 per 1000 cases, aRR 2.4, 95% CI 1.5-4.0)
•Death (1.5 versus 1.2 per 1000 cases, aRR 1.7, 95% CI 1.2-2.4)
Women with co-morbidities and older women appeared to be at particularly elevated risk of adverse maternal outcome. Some limitations of the study included ascertainment biases; lack of information on pregnancy status in over one-half of reported cases; and lack of information for the reason for hospital admission in many cases, limiting the ability to distinguish between admissions solely for labor and delivery and those for COVID-19-related illness.
●In contrast with most COVID-19 studies of pregnant and postpartum patients, PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) is an ongoing prospective nationwide study in the United States, and 95 percent of participants to date were outpatients:
•The most prevalent first symptoms in the 594 patients who tested positive for SARS-CoV-2 infection were:
- cough (20 percent),
- sore throat (16 percent),
- body aches (12 percent)
- fever (12 percent).
•Median time to symptom resolution was 37 days, but symptoms persisted for ≥8 weeks in 25 percent of participants.
Patients self-referred to the study and reported their symptoms; thus, these data may be affected by selection bias but may also provide more accurate reflection of which symptoms are important to patients as compared with relying on a medical record.Frequency of congenital infection — The extent of vertical transmission remains unclear. Only a few well-documented cases of probable vertical transmission have been published . Many other possible cases of congenital infection have been reported in the setting of third-trimester maternal infection within 14 days of delivery, suggesting congenital infection is uncommon (approximately 2 percent of maternal infections ). In a systematic review of infants born to 936 COVID-19-infected mothers, neonatal viral RNA testing was positive in 27/936 (2.9 percent) nasopharyngeal samples taken immediately after birth or within 48 hours of birth, 1/34 cord blood samples, and 2/26 placental samples; in addition, 3/82 neonatal serologies were immunoglobulin M (IgM) positive for SARS-CoV-2 . In a CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team report of pregnant persons with laboratory-confirmed SARS-CoV-2 infection, 2.6 percent of the 610 infants with available SARS-CoV-2 test results had a positive test, primarily those born to women with infection at delivery .Viremia rates in patients with COVID-19 appear to be low (1 percent in one study ) and transient, suggesting placental seeding and vertical transmission would not be common. Most placentas studied so far had no evidence of infection, but the virus has been identified in a few cases and one patient with a positive vaginal swab and one patient with a positive vaginal swab and amniotic fluid have been reported [ .SARS-CoV-2 cell entry is thought to depend on the angiotensin-converting enzyme 2 receptor and serine protease TMPRSS2, which are minimally coexpressed in the placenta . This may account for the infrequent occurrence of placental SARS-CoV-2 infection and fetal transmission.One barrier to diagnosis of maternal-fetal transmission is that there are no accepted criteria for definitive evidence of congenital infection. Criteria for vertical transmission should distinguish between intrauterine versus intrapartum/postnatal transmission of SARS-CoV-2.We generally agree with the criteria proposed by Shah et al, which takes into account maternal symptoms and epidemiologic exposure, results of maternal testing, clinical status of the neonate at birth, and results of neonatal testing :
●Congenital infection in an intrauterine fetal death/stillbirth can be diagnosed by positive polymerase chain reaction (PCR) from fetal tissue or the fetal side of the placenta, or electron microscopy to detect viral particles in fetal tissue or the fetal side of the placenta, or culture to detect viral growth in fetal tissue or the fetal side of the placenta. Congenital infection would be unlikely if only tests from the maternal side of the placenta are positive (ie, no other sites of testing or no detection of the virus in fetal tissue or the fetal side of the placenta).
●Congenital infection in a newborn can be diagnosed if virus is detected by PCR in umbilical cord blood or neonatal blood collected within the first 12 hours of birth or amniotic fluid collected prior to rupture of membranes.By comparison, intrapartum transmission of infection is diagnosed if SARS-CoV-2 PCR of a nasopharyngeal swab at birth (after cleaning the infant) and at 24 to 48 hours of age are both positive and postnatal transmission of infection is diagnosed if SARS-CoV-2 PCR of a respiratory sample at birth is negative but SARS-CoV-2 PCR of a nasopharyngeal/rectal swab is positive at 24 to 48 hours of age. Blumberg et al have also published reasonable criteria for intrauterine, intrapartum, and postnatal transmission
Pregnancy and newborn outcome
●Risk of miscarriage – The frequency of miscarriage does not appear to be increased, but data on first- and second-trimester infections are limited.
●Overall preterm and cesarean delivery rates – Preterm birth and cesarean delivery rates have been increased in many studies, but not all . Fever and hypoxemia may increase the risks for preterm labor, prelabor rupture of membranes, and abnormal fetal heart rate patterns, but preterm deliveries also occur in patients without severe respiratory disease. It appears that many third-trimester cases are electively delivered by cesarean because of a bias to intervene catalyzed by the belief that management of severe maternal respiratory disease would be improved by delivery; however, this hypothesis is unproven.In a systematic review including over 11,000 pregnant and recently pregnant persons with suspected or confirmed COVID-19, 17 percent delivered before 37 weeks of gestation and 65 percent delivered by cesarean [7]. Most preterm deliveries were iatrogenic; only 6 percent were spontaneous.In the CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team report described above, the overall preterm delivery among 3913 live births to hospitalized patients with SARS-CoV-2 infection was 12.9 percent (which was higher than a national estimate of 10.2 percent), and was similar for symptomatic and asymptomatic mothers . The overall rate of cesarean delivery was 34 percent (rate in symptomatic and asymptomatic mothers: 34.6 and 31.6 percent, respectively), which is slightly above the cesarean delivery rate (31.9 percent) in the United States.
●Outcome by severity of maternal disease – In a study that specifically reported outcome by disease severity, 32 of the 64 pregnant women hospitalized for severe or critical COVID-19 delivered during the course of infection; 9 of 44 women with severe disease and 13 of the 20 women with critical disease were delivered because of the maternal status while only three deliveries were for fetal status [40]. Birth was preterm in 9 percent of women with severe disease and 75 percent of those with critical disease.
●Fetal outcome – An increased risk for congenital anomalies has not been reported .In a prospective cohort in the United Kingdom, the stillbirth rate among infected women was almost three times the national rate (11.5 versus 4.1 per 1000 total births), although these results are negatively skewed because severely ill women were often delivered while less severely ill patients with ongoing pregnancies were not counted. In the United States, the stillbirth rate among hospitalized pregnant patients with SARS-CoV-2 infection is approximately 3 percent , but 0.4 percent among the overall population of pregnant patients with laboratory-confirmed SARS-CoV-2 infection .By comparison, the overall rate of stillbirth in the United States is 0.6 percent. There is limited information on the reasons for the increase in stillbirth. Severe and critical maternal illness likely accounted for some stillbirths, and others may have been related to disruptions in prenatal care and to a higher frequency of home birth . Lupus anticoagulant is part of the evaluation of stillbirth and also has been found transiently in patients with COVID-19.
●Newborn outcome – Over 95 percent of newborns have been in good condition at birth, consisting of mostly asymptomatic or mild infection (ie, not requiring respiratory support). Neonatal morbidity has largely been related to preterm birth and to adverse uterine environments resulting from critical maternal disease .Reproductive decision-making — The COVID-19 pandemic has prompted questions about whether women should consider postponing pregnancy because of potential virus-related risks to maternal and newborn health. Given the information above I believe that reproductive decisions (eg, pregnancy planning, pregnancy termination) should not be based primarily on health-related COVID-19 concerns. As others have pointed out, pregnancy-related risks associated with the virus have not been well-established, limited evidence suggests that pregnancy-related risks are not high or substantially above the risk associated with other conditions or exposures that are fairly common among pregnant women, and pregnancy-related risks can be reasonably minimized or mitigated by standard preventive measures.
APPROACH TO DIAGNOSIS
The approach to diagnosis is similar to that in the general population. Whom to test, specimen collection, types of tests and factors affecting test performance, test interpretation, follow-up/repeat testing, use of serology to identify prior/late infection, and discontinuation of infection control precautions are discussed in detail separately. Patients should be screened for clinical manifestations consistent with COVID-19 (eg, cough, fever, myalgias, sore throat, dyspnea, anosmia/hyposmia) prior to entry into a health care facility. In areas where the infection is prevalent, we believe testing all patients upon presentation to labor and delivery with a rapid test for SARS-CoV-2 is reasonable, if testing is available. Patients with scheduled inductions and cesarean deliveries can be tested within 72 hours of the scheduled admission.
The evaluation of hospitalized patients with documented or suspected COVID-19 should focus on features associated with severe illness and identify organ dysfunction or other co-morbidities that could complicate potential therapy. The evaluation is the same regardless of pregnancy status. A portable chest radiograph is sufficient for initial evaluation of pulmonary complications and extent of lung involvement in hospitalized patients with COVID-19. A single chest radiograph carries a very low fetal radiation dose of 0.0005 to 0.01 mGy. Computed tomography (CT) should be performed, if indicated, as the fetal radiation dose for a routine chest CT is also low and not associated with an increased risk of fetal anomalies or pregnancy loss. Some authorities have advocated lung ultrasound, possibly at the same time as the obstetric scan, for quick diagnosis of pneumonia in symptomatic pregnant women . A detailed description of performance of lung ultrasound, which appears to have good diagnostic accuracy and has fewer infection control implications than CT, can be found elsewhere
DIFFERENTIAL DIAGNOSIS
●Other infections – Early symptoms of COVID-19 can be similar to those of multiple other viral and bacterial respiratory infections (eg, influenza, adenovirus, Haemophilus influenzae pneumonia, Mycoplasma pneumoniae pneumonia). In a systematic review including over 11,000 pregnant and recently pregnant persons with suspected or confirmed COVID-19, only 18 percent of symptomatic women tested positive for SARS-CoV-2. If influenza is circulating in the community, it is reasonable to also test for influenza when testing for SARS-CoV-2 as this could have management implications. Detection of another pathogen does not necessarily rule out SARS-CoV-2 in locations where there is widespread transmission as coinfection with SARS-CoV-2 and other respiratory viruses, including influenza, has been described. Coinfection with tuberculosis has also been reported and should be considered in patients with impaired immunity or at increased risk for exposure to Mycobacterium tuberculosis.
●Preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome – In pregnant women, some COVID-19-related laboratory abnormalities (elevated liver enzyme levels, thrombocytopenia) are identical to those that occur in preeclampsia with severe features and HELLP syndrome. Autoimmune hemolysis; prolonged prothrombin time; elevated D-dimer, procalcitonin, and C-reactive protein (CRP) levels; positive lupus anticoagulant screen; and low fibrinogen levels may also be observed in complicated COVID-19 cases (note the normal reference ranges for D-dimer, CRP, and fibrinogen levels are higher in pregnant women). Symptoms also overlap: Headache, acute cerebrovascular disease, and seizures can be neurologic manifestations of COVID-19, as well as findings in preeclampsia with severe features/eclampsia.Therefore, these diagnoses should also be considered and may coexist with COVID-19 . The presence of acute hypertension can be helpful as it is a common finding in patients with preeclampsia or HELLP syndrome and not a feature of COVID-19 (chronic hypertension is a risk factor for severe illness). In patients with severe SARS-CoV-2 pneumonia plus clinical findings that have been associated with both severe COVID-19 and preeclampsia, uterine artery pulsatility index above the 95th centile for gestational age and soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ≥85 (at <34 weeks) or ≥110 (at ≥34 weeks) support the diagnosis of preeclampsia. In a small observational report, these markers were normal in five of the six patients in whom the symptoms of preeclampsia resolved upon improvement of the maternal infection. Although acute kidney injury can occur as a severe complication of COVID-19 and can also be a severe complication of obstetric disorders, such as preeclampsia with severe features, abruptio placentae, or hemorrhagic shock, uterine bleeding is a prominent feature of the latter two disorders but not for COVID-19 or preeclampsia.
PRENATAL CARE
Uninfected pregnant persons — The American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and others have issued guidance regarding prenatal care during the COVID-19 pandemic (available at acog.org and SMFM.org and rcog.org) . It includes general guidance for testing and preventing spread of COVID-19, algorithms, and suggestions for modifying traditional protocols for prenatal visits. These modifications, which should be tailored for low- versus high-risk patients (eg, multiple gestation, hypertension, diabetes), include telehealth in areas of active infection transmission , reducing the number of in-person visits, timing of visits, limiting the number of persons in waiting rooms and physical distancing, grouping tests for the same visit/day (eg, aneuploidy, diabetes, infection screening) to minimize maternal contact with others, restricting visitors during visits and tests, timing of indicated obstetric ultrasound examinations (eg, gestational age, fetal anomaly, fetal growth, placental attachment), and timing and frequency of use of nonstress tests and biophysical profiles. As discussed above, there is limited information on the effects of these modifications on maternal and pregnancy outcomes, but after lockdown, some countries reported increased rates of stillbirth, which may have been related to disruptions in prenatal care and to a higher frequency of home birth .There are many ways to reduce the time patients, including patients with high-risk pregnancies, are in the office. For example, the clinician can order a 75 gram two-hour oral glucose tolerance test (GTT) instead of a glucose challenge test and 100 gram three-hour GTT (in women with positive results); cell-free DNA screening can be used (at >10 weeks) for Down syndrome screening rather than the combined test (ie, nuchal translucency on ultrasound and serum analytes). Ideally, every woman should have telehealth capabilities and a means for measuring blood pressure at home.The psychological impact of COVID-19 should also be recognized and support offered. The COVID-19 pandemic may be associated with new onset or exacerbation of subsyndromal psychiatric symptoms as well as full-blown psychiatric disorders, including anxiety disorders, depressive disorders, posttraumatic stress disorder, or substance use disorders.
Asymptomatic patients — Care of asymptomatic patients with confirmed or probable SARS-CoV-2 infection involves assessing their risk for developing severe disease, close monitoring for respiratory decompensation (which may occur rapidly), infection control and self-isolation for the anticipated duration of illness, and appropriate timing of discontinuation of precautions. These issues are reviewed elsewhere.
Symptomatic patients — The clinical care of symptomatic patients depends on illness severity, underlying medical comorbidities, coexistent pregnancy complications, and social situation (eg, ability for self-care and follow-up). If the patient is admitted because of severe COVID-19, a multidisciplinary team can help determine the most appropriate location (medical or obstetric ward, labor and delivery, or intensive care unit).Home careOverview — Most (at least 86 percent) pregnant patients with known or suspected COVID-19 have mild disease (no shortness of breath) that does not warrant hospital-level care in the absence of obstetric problems (eg, preterm labor), concern for rapid deterioration, inability to promptly return to the hospital, or, possibly, inability to self-isolate.These patients should be followed closely for progression to severe or critical disease and given instructions for infection control, symptom management, warning symptoms, and obstetric follow-up (at least once within two weeks of COVID-19 diagnosis ). Patients experiencing homelessness should be provided resources, such as dedicated housing units, where available. It is important to note that infection with SARS-CoV-2 may cause catastrophic illness in any patient, even among those without risk factors for severe disease.
When to call your doctor? — Patients should call their provider (or seek emergency medical care) if they experience worsening dyspnea (difficulty breathing), unremitting fever >39°C /100.4 F despite appropriate use of acetaminophen (tylenol), inability to tolerate oral hydration and medications, persistent pleuritic chest pain, confusion, or obstetric complications (eg, preterm contractions, vaginal bleeding, rupture of membranes) . Those in the third trimester should perform fetal kick counts and report decreased fetal movement. The US Food and Drug Administration (FDA) has expanded its approval for use of noninvasive fetal and maternal monitoring devices in the home in patients who require fetal and/or maternal monitoring for conditions unrelated to COVID-19. This can help reduce patient and health care provider contact and potential exposure to COVID-19 during the pandemic.
Supportive care and medications — Home care is generally supportive, similar to that advised for other acute viral illnesses. Hydration, adequate rest, and frequent ambulation with more advanced activity as soon as tolerated are advised.
-Bamlanivimab is a neutralizing monoclonal antibody available as an option for the treatment of non-hospitalized patients with mild to moderate COVID-19 who are at high risk for progressing to severe disease and/or hospitalization. It should not be withheld from pregnant patients who are deemed to be at high risk for progression to severe disease if they would otherwise qualify for its use, after a discussion of the potential benefits and theoretic risks. Placental transfer of bamlanivimab may be expected since human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier. Nonclinical reproductive toxicity studies have not been performed, and there is no information regarding whether the potential transfer of bamlanivimab provides any treatment benefit or risk to the developing fetus.The combination casirivimab-imdevimab is another monoclonal antibody option for non-hospitalized COVID-19 patients. Pregnancy implications are not well defined and are the same as those described above for bamlanivimab.
Hospital care- Candidates for inpatient care which is highly dependent on bed availability at the local hopsital — Inpatient monitoring and care is appropriate for pregnant COVID-19 patients with:
●Mild symptoms (fever, cough, sore throat, malaise, headache, muscle pain without shortness of breath, dyspnea, or abnormal chest imaging) plus a comorbid condition (eg, poorly controlled hypertension or diabetes, chronic kidney disease, chronic cardiopulmonary disease, immunosuppressive states [intrinsic or medication-related]).
●Fever >39°C despite use of acetaminophen (which raises concern for cytokine storm syndrome).
●Moderate or severe signs and symptoms (eg, oxygen saturation <95 percent [when pulse oximetry is available] on room air and while walking, respiratory frequency >30 breaths per minute, rapidly escalating supplemental oxygen requirement).
●Critical disease – Respiratory failure, hypotension despite appropriate hydration, and/or new end-organ dysfunction (eg, mental status changes, hepatic or renal insufficiency, cardiac dysfunction).Pregnant hospitalized patients with severe disease, an oxygen requirement plus comorbidities, or critical disease should be cared for by a multispecialty team at a level III or IV hospital with obstetric services and an adult intensive care unit (ICU). COVID-19 status alone is not necessarily a reason to transfer non-critically ill pregnant women with suspected or confirmed COVID-19.
Maternal respiratory support — Patients with severe disease often need oxygenation support. Among critically ill COVID-19 patients, profound acute hypoxemic respiratory failure from acute respiratory distress syndrome (ARDS) is the dominant finding. General supportive care of the critically ill patient with COVID-19 pneumonia is similar to that in patients with ARDS due to other causes. During pregnancy, maternal peripheral oxygen saturation (SpO2) should be maintained at ≥95 percent, which is in excess of the oxygen delivery needs of the mother. If SpO2 falls below 95 percent, an arterial blood gas may be obtained to measure the partial pressure of oxygen (PaO2): Maternal PaO2 greater than 70 mmHg is desirable to maintain a favorable oxygen diffusion gradient from the maternal to the fetal side of the placenta. The World Health Organization (WHO) suggests maintaining maternal SpO2 ≥92 to 95 percent once the patient is stable .In the ICU, severely ill patients with COVID-19 are often managed in the prone position; the left lateral position is an alternative but may not be as effective. Some ICUs have extended this approach to pregnant women, although even a semiprone position can be a difficult position in which to place a pregnant woman in the last half of pregnancy . Padding above and below the gravid uterus >24 weeks is desirable to offload the uterus and avoid aortocaval compression. Permissive hypercapnia (PCO2 <60 mmHg) and extracorporeal membrane oxygenation (ECMO), if indicated for management of ARDS, do not appear to be harmful to the fetus, but data are limited . High positive end-expiratory pressure strategies (>10 mmHg), if considered, require close ongoing maternal and fetal monitoring because they decrease preload and cardiac output.Common complications of COVID-19-related ARDS include acute kidney injury, elevated liver enzymes, and cardiac injury (eg, cardiomyopathy, pericarditis, pericardial effusion, arrhythmia, sudden cardiac death).
Use and type of VTE prophylaxis — Direct data on risk of venous thromboembolism (VTE) related to COVID-19 are limited but suggest an increased risk (3 cases of VTE among 637 hospitalized infected pregnant patients in one systematic review. Pregnancy, reduced mobility, and dehydration can contribute to this risk.Prophylactic-dose anticoagulation is recommended for pregnant patients hospitalized for severe COVID-19, if there are no contraindications to its use, and generally discontinued when the patient is discharged to home. Patients with COVID-19 who do not warrant hospitalization for the infection or who are asymptomatic or mildly symptomatic and hospitalized for reasons other than COVID-19 do not require anticoagulation. However, if antithrombotic therapy is prescribed during pregnancy for another indication, this therapy should be continued if the patient receives a diagnosis of COVID-19. Decisions regarding VTE prophylaxis in the pregnant and postpartum patient should be individualized, considering concomitant VTE risk factors. Unfractionated heparin is generally preferred for pregnant patients who might be proximate to delivery because it is more readily reversed than low molecular weight heparin (LMWH). For these patients and those who have a contraindication to LMWH, prophylactic unfractionated heparin can be used: 5000 units in the first trimester, 7500 to 10,000 units in the second trimester, and 10,000 units in the third trimester, administered subcutaneously every 12 hours (reduce if the activated partial thromboplastin time is elevated). For pregnant patients who are unlikely to be delivered within a few days, prophylactic- or intermediate-dose LMWH is reasonable (eg, enoxaparin 40 mg subcutaneously daily or 1 mg/kg [commonly rounded to the nearest 10 mg] subcutaneously every 24 hours). Intermittent pneumatic compression is suggested when pharmacologic prophylaxis is contraindicated. Patient evaluation (inpatients, outpatients), anticoagulation for various patient groups, and dosing in COVID-19 are discussed in more detail separately.
Use of dexamethasone — Dexamethasone 6 mg daily for 10 days or until discharge is recommended for severely ill nonpregnant patients who are on supplemental oxygen or ventilatory support. Glucocorticoids may also have a role in the management of refractory shock in critically ill patients with COVID-19.In pregnant patients who meet criteria for use of glucocorticoids for maternal treatment of COVID-19 and also meet criteria for use of antenatal corticosteroids to induce fetal maturity, we suggest administering the usual doses of dexamethasone (four doses of 6 mg intravenously 12 hours apart) to induce fetal maturation and continue maternal treatment to complete the course of dexamethasone (6 mg orally or intravenously daily for 10 days or until discharge, whichever is shorter). Others have suggested using glucocorticoids such as methylprednisolone or hydrocortisone to complete the course of maternal treatment because they result in less fetal steroid exposure. This is a reasonable alternative approach; however, the efficacy of such steroids for reducing maternal mortality is less clear. Criteria for glucocorticoid administration and efficacy data for different steroids are reviewed separately.
Use of NSAIDs and acetaminophen — ACOG, WHO, and the European Medicines Agency (EMA) recommend not avoiding nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 patients when clinically indicated. The lowest effective dose is used, ideally for less than 48 hours and guided by gestational age-related potential fetal toxicity (eg, oligohydramnios, premature closure of the ductus arteriosus). Low-dose aspirin for prevention of preeclampsia is safe throughout pregnancy. NSAIDs are commonly used for treatment of fever and pain; however, there are anecdotal reports of possible negative effects of NSAIDs in patients with COVID-19. Given the uncertainty, we use acetaminophen as the preferred antipyretic and analgesic agent, if possible. In patients with abnormal liver chemistries secondary to COVID-19, a potential concern of acetaminophen use is hepatic toxicity. However, doses less than 2 grams per day are likely safe in the absence of severe or decompensated hepatic disease.Concern about possible negative effects of NSAIDs in COVID-19 patients was raised by anecdotal reports of a few young, nonpregnant patients who received NSAIDs (ibuprofen) early in the course of infection and experienced severe disease [77,78]. Clinical or population-based data on the risk of NSAIDs remain limited. In an observational study of patients hospitalized for COVID-19 in South Korea, use of NSAIDs in the seven days prior to hospitalization was associated with worse outcomes compared with nonuse; however, patients who used NSAIDs were older and more likely to have underlying comorbidities, and other reasons for NSAIDs use may have confounded the findings [79]. A retrospective study from Israel found no association between NSAID use and worse outcomes compared with acetaminophen use or no antipyretic use.
Use of acetaminophen in pregnancy, including in the first trimester, has been shown overall to be safe and may attenuate the pregnancy risks associated with fever exposure. Hyperthermia, which is common in COVID-19, is a theoretical concern as elevation of maternal core temperature from a febrile illness during organogenesis in the first trimester may be associated with an increased risk of congenital anomalies, especially neural tube defects, or miscarriage; however, an increased incidence of these outcomes has not been observed. Safety of antiviral drug therapy — Several agents are being evaluated for treatment of COVID-19. Although some of these agents are clinically available for other indications, their use for COVID-19 remains investigational. Very few trials of drugs for treatment of COVID-19 include pregnant women (eg, SOLIDARITY trial [81], RECOVERY trial [82]).
●Remdesivir – For pregnant patients who would otherwise qualify for remdesivir (and for whom it is available), remdesivir is recommended. Indications for use are described separately. Remdesivir is a novel nucleotide analog that has activity against SARS-CoV-2 in vitro [83] and related coronaviruses (including severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome-related coronavirus [MERS-CoV]) both in vitro and in animal studies. It has been used without reported fetal toxicity in some pregnant women with Ebola and Marburg virus disease and is being used to treat pregnant patients with severe COVID-19 . Almost all randomized trials of the drug during the COVID-19 pandemic have excluded pregnant and breastfeeding women.
●Other drugs – Several other drugs are being used in research studies (eg, monoclonal antibodies, hyperimmune globulin). Ribavirin is an investigational drug for COVID-19 that is known to be teratogenic and should be avoided. Drugs that may be considered include:•Baricitinib – Baricitinib (a JAK inhibitor) is available for emergency use in combination with remdesivir for treatment of hospitalized adults and children. Decisions about baricitinib administration in pregnancy need to be made with consideration of the potential maternal benefit and the theoretic fetal risks. Factors that may weigh into shared decision making include severity of maternal status, underlying risk factors, and gestational age. Placental transfer of baricitinib may be expected based on molecular weight. Information on use of baricitinib in pregnancy is limited to a case report and registry data of inadvertent administration during pregnancy. These limited human data are insufficient to inform a drug-associated risk for major birth defects or miscarriage. Embryo-fetal toxicity, such as skeletal anomalies and reduced fertility, have been observed in animals dosed in excess of the maximum human exposure.
•Bamlanivimab and casirivimab-imdevimab – Bamlanivimab and the combination casirivimab-imdevimab are monoclonal antibody therapies available as options for the treatment of nonhospitalized patients.
•Hydroxychloroquine or chloroquine – Data from randomized trials generally suggest no benefit from administration of hydroxychloroquine or chloroquine. Furthermore, adverse maternal effects include abnormal heart rhythms (QT interval prolongation and ventricular tachycardia), especially in patients taking other drugs associated with QTc prolongation. Hydroxychloroquine crosses the placenta. Accumulation in fetal ocular tissue has been observed in animal studies, but an increased risk of fetal ocular abnormalities has not been observed in humans, which is reassuring given that the drug has been used by pregnant women for treatment of systemic lupus erythematosus or for prevention of malaria. Available data are limited, however, and a risk to the fetus cannot be ruled out when used at different doses (particularly ≥400 mg) for other indications [88,89].
Convalescent plasma — Convalescent plasma is one approach that may be combined with other aspects of disease-specific and supportive care. Decision-making about whether to use convalescent plasma in a particular patient group is discussed in detail separately. : Convalescent plasma and hyperimmune globulin".)Convalescent plasma has been used successfully in a few pregnant women, sometimes with drug therapy (eg, steroids, remdesivir, lopinavir/ritonavir, and azithromycin). When possible, it should be administered as part of a clinical trial that can assess safety and efficacy. In the United States, two trials at the University of Pennsylvania are studying the effects of convalescent plasma in COVID-19 patients and are open to pregnant women who meet inclusion criteria (https://clinicaltrials.gov/ct2/show/NCT04397757 and https://clinicaltrials.gov/ct2/show/NCT04388527).Fetal monitoring — A specific management issue in pregnant patients is fetal monitoring in those who are at a viable gestational age (ie, gestational age when delivery for fetal indications and neonatal resuscitation would be considered). The need for and frequency of fetal testing depend on gestational age, stability of maternal vital signs and oxygenation, other maternal comorbidities, and discussions with the patient and the family that consider the possibly increased risks of stillbirth and perinatal morbidities in the absence of testing.For hospitalized patients, a Bluetooth-enabled external fetal monitor can transmit the fetal heart rate tracing to the obstetric provider. The monitor can be used continuously in unstable hospitalized patients in whom emergency cesarean delivery would be performed for a persistent nonreassuring fetal heart rate pattern. An abnormal tracing might also help guide maternal oxygen therapy. In patients with stable oxygen saturation (SaO2), a nonstress test can be performed once or twice daily, as one option.Monitoring for preterm labor — Monitoring pregnant patients for signs and symptoms of preterm labor is a routine component of obstetric care and should be a component of maternal monitoring of pregnant patients hospitalized in nonobstetric settings.
Follow-up after recovery
●Maternal – Patients with COVID-19 generally warrant outpatient follow-up through telehealth or an in-person visit within one to two days following discharge to home.
●Fetal – Development of fetal growth restriction is a theoretic concern and has been described with other SARS infections. Very limited COVID-19-specific data on fetal growth after maternal infection are available . Although significant placental histopathologic changes are not universally present, suboptimal fetal growth due to placental insufficiency is plausible because maternal COVID-19 has been associated with uteroplacental vascular malperfusion, including acute and chronic intervillous inflammation, focal avascular villi, and thrombi in larger fetal vessels in the chorionic plate and stem villi . These lesions could be caused by COVID-19-related coagulopathy, placental hypoxia during the acute maternal illness, placental viral infection, or a combination of these factors.In the absence of robust data, authorities have suggested that pregnant persons with confirmed infection should have at least one ultrasound assessment of fetal amniotic fluid volume, beginning in the third trimester and at least 14 days after symptom resolution . For those with first- or early second-trimester infection, a detailed fetal morphology scan at 18 to 23 weeks of gestation is also indicated.Antenatal testing (nonstress test, biophysical profile) can be reserved for routine obstetric indications [59].Timing of delivery — Timing of delivery should be individualized based on maternal status, concurrent disorders, gestational age, and shared decision-making with the patient or health care proxy.
●Nonsevere illness•For asymptomatic or mildly symptomatic patients positive for COVID-19 at ≥39 weeks of gestation, delivery can be considered to decrease the risk of worsening maternal status before the onset of spontaneous labor.
•For most patients with preterm COVID-19 and nonsevere illness who have no medical/obstetric indications for prompt delivery, delivery is not indicated and ideally will occur sometime after a negative testing result has been obtained or isolation status has been lifted, thereby minimizing the risk of postnatal transmission to the newborn.
•For most patients with preterm COVID-19 and nonsevere illness who also have medical/obstetric complications (eg, prelabor rupture of membranes, preeclampsia), the timing of delivery is, in general, determined by usual protocols for the specific medical/obstetric disorder.
●Severe/critical illness – For women with severe illness, there are multiple issues to consider, and timing of delivery needs to be individualized. Whether the mother's respiratory disease will be improved by delivery and the risk of postnatal transmission in the delivery room when maternal symptoms are acute are both unclear. It should also be noted that maternal antibody production and, in turn, passive newborn immunity may not have had time to develop. On the other hand, increased oxygen consumption and reduced functional residual capacity, which are normal in pregnancy, may facilitate maternal deterioration in patients with pneumonia [104]. Excessive uterine distension from multiple gestation or severe polyhydramnios in the third trimester may further compromise pulmonary function.For the hospitalized patient with COVID-19 with pneumonia but not intubated, some authorities have advocated consideration of delivery in pregnancies >32 to 34 weeks in the setting of worsening status. The rationale is that delivery is performed before the pulmonary situation worsens and ongoing maternal hypoxemia places the fetus at risk of compromise. Most authorities do not advocate delivery prior to 32 weeks, even though the maternal situation may worsen in the second week, given the known morbidity and mortality of very preterm infants.Timing of delivery of the hospitalized pregnant woman intubated and critically ill with COVID-19 is challenging. After 32 to 34 weeks, some have advocated delivery if the patient is stable to avoid any pregnancy-related problems if the maternal condition subsequently deteriorates, but this could exacerbate the maternal condition. Others consider delivery only for patients with refractory hypoxemic respiratory failure or worsening critical illness [71]. Between viability and <30 to 32 weeks, as long as the maternal condition remains stable or improving, continuing maternal support with fetal monitoring is usually suggested to avoid neonatal morbidity/mortality and possibly maternal morbidity from iatrogenic preterm birth. In some situations (eg, refractory COVID-19-related respiratory failure), maternal ECMO may be necessary [73,105].Route of delivery, management of labor and delivery, and postpartum maternal and infant care are reviewed separately.
PREGNANCY REGISTRIES
Registries are being developed to collect data of how COVID-19 affects pregnancy and newborns. For example:
●Pregnancy CoRonavIrus Outcomes RegIsTrY (PRIORITY) is the official United States registry led by the University of California, San Francisco. Providers and patients can send information via priority.ucsf.edu.
●International Registry of Coronavirus Exposure in Pregnancy (IRCEP) is a registry led by an international group of investigators.SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
SUMMARY AND RECOMMENDATIONS
●Pregnant women should follow the same recommendations as nonpregnant persons for avoiding exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). (See 'Prevention' above.)
●Clinical manifestations of COVID-19 in pregnant women are generally similar to those in nonpregnant individuals (table 1). A positive test for SARS-CoV-2 generally confirms the diagnosis of COVID-19, although false-positive and false-negative tests are possible.
●Pregnancy does not appear to increase susceptibility to infection, and most infected mothers recover without undergoing delivery. However, pregnant women appear to be at increased risk for severe disease necessitating maternal intensive care unit (ICU) admission and mechanical ventilation, and in rare cases, extracorporeal membrane oxygenation (ECMO) may be needed. Risk factors for severe disease include age ≥35 years, obesity, hypertension, and preexisting diabetes. Maternal deaths have been reported but not in excess of those in nonpregnant women of reproductive age.
●Infected women, especially those who develop pneumonia, appear to have an increased frequency of preterm birth and cesarean delivery. These complications are likely related to severe maternal illness. Whether intrauterine infection occurs is still under investigation. A few early newborn infections and placental infections have been reported, suggesting possible but uncommon vertical transmission. Postnatal contamination could not be excluded conclusively.
●The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) have issued guidance regarding prenatal care during the COVID-19 pandemic (available at acog.org and SMFM.org), including general guidance for testing and preventing spread of COVID-19, suggestions for modifying traditional protocols for prenatal and postnatal visits and hospital discharge, and algorithms for assessment and management. These modifications are tailored for low- versus high-risk pregnancies.
●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). (See 'Use of dexamethasone' above.)
●For pregnant patients hospitalized for severe COVID-19, prophylactic-dose anticoagulation is recommended, if there are no contraindications to its use, and generally discontinued when the patient is discharged to home.
●For most women with preterm COVID-19 and nonsevere illness who have no medical/obstetric indications for prompt delivery, delivery is not indicated and ideally will occur sometime after a negative testing result is obtained or isolation status is lifted, thereby minimizing the risk of postnatal transmission to the neonate. Severely ill patients at least 32 to 34 weeks of gestation with COVID-19 pneumonia may benefit from early delivery.
●Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for treatment of fever and pain; however, there are anecdotal reports of possible negative effects of NSAIDs in patients with COVID-19. Given the uncertainty, we use acetaminophen as the preferred antipyretic and analgesic agent, if possible. If NSAIDs are needed, the lowest effective dose is used and, in undelivered patients, guided by gestational age-related potential toxicity for the fetus.
●Several agents are being evaluated for treatment of COVID-19. Remdesivir is the most promising and has been used without reported fetal toxicity in some severely ill pregnant women.