Brigham and Women's Hospitals

Obstetrics

Updated: April 20, 2020

Health care providers are encouraged to enroll females exposed to COVID-19 during pregnancy in the PRIORITY registry (Pregnancy CoRonavIrus Outcomes RegIsTrY)

Information for pregnant patients about COVID-19 in 7 different languages can be found online via Pregistry here.

Clinical Presentation and Clinical Course of COVID-19 in Pregnancy

Clinical Presentation

  1. Like non-pregnant patients, the most common presenting symptoms are fever and cough (see Clinical Course) (Zaigham, Acta Obstet Gynecol Scand, 2020; Wu et al, JAMA 2020, Liu et al, AJR 2020)
  1. About 85% will have mild disease, 10% severe disease and 5% critical disease (Breslin et al, Am J Obstet Gynecol MFM, 2020)
  2. A cohort of 118 pregnant women from China revealed 92% had mild disease, 7% severe disease, and 1% critical disease. Rates of severe disease were reported to be 16% among all people in China (Chen, NEJM, 2020)
  3. Comorbidities, such as obesity, diabetes, asthma, hypertension may make pregnant women more susceptible to effects of COVID-19 (ACOG COVID –19 FAQs for Obstetrician Gynecologists).
  1. Diagnostic Considerations: This clinical presentation mirrors other diseases in pregnancy.
  1. If a patient is presenting with COVID-like symptoms, particularly a fever, a high clinical suspicion for alternative or comorbid processes such as chorioamnionitis or influenza is needed.
  1. Laboratory derangements may overlap with other obstetric diagnoses (e.g. transaminitis and pulmonary findings can confound a diagnosis of preeclampsia or HELLP syndrome.
  1. If a patient develops new signs / symptoms during hospitalization or labor, COVID-19 needs to be considered regardless of a priori risk of other common infectious processes (such as epidural fever or chorioamnionitis).
  1. In a study from two New York hospitals with universal testing 10 of 14 patients who were asymptomatic at admission became symptomatic during hospitalization with fever as the primary complaint (Breslin et al, Am J Obstet Gynecol MFM, 2020).
  1. Asymptomatic Infection: Patients may present early in their infectious course prior to symptoms, or may have asymptomatic viral carriage.
  1. In a series of 43 COVID-19 infected pregnant women in New York, 32.6% of them presented WITHOUT symptoms. Of these, 46.2% developed symptoms within 7 days after the positive test (Breslin et al, Am J Obstet Gynecol MFM, 2020).
  2. A recent series of 215 pregnant patients from New York demonstrated a 13.7% rate of positive testing for SARS-CoV-2 amongst asymptomatic women.
  1. Twenty-nine of the 33 patients who were positive for the virus were asymptomatic (Sutton et al, NEJM, 2020).
  2. Asymptomatic women tested on labor and delivery had positive results for SARS-CoV-2 at a rate <5%.

Maternal and Obstetric Outcomes

  1. Experience with COVID in pregnancy is limited. Data to date is based in case-series and not controlled. The background comorbidities in the population, local testing policies, and obstetric care practices may limit generalizability to our population.
  2. In pregnant women with viral pneumonias due to non-COVID viruses such as influenza, pregnant women demonstrate increased susceptibility to infection and higher rates of mortality (Callaghan et al, Obstet Gynecol, 2015) However, thus far, COVID-19 (SARS-CoV-2) appears to have less severe maternal pregnancy outcomes than SARS-CoV-1 or MERS (Schwartz et al, Viruses, 2020).
  1. There are approximately 100 cases of SARS from 2002-2003 in pregnancy reported in the literature. There was a strong association with severe manifestations of disease in pregnant compared to nonpregnant individuals (Lam et al, BJOG, 2004).
  2. Only 11 pregnancy-associated cases of MERS were reported from the 2012 outbreak, with a 91% rate of severe maternal morbidity (compared to a background severe maternal morbidity rate of 2-3%) (Schwartz et al, Viruses, 2020).
  1. While the data is limited, COVID-19 appears to have somewhat less of a severe presentation than SARS or MERS, but is associated with variable rates of maternal and obstetric complications:
  1. In a systematic review of 18 articles reporting on 108 pregnancies affected by COVID-19 infection:
  1. 3 women were admitted to the ICU
  2. 1 experienced a neonatal demise
  3. 1 experienced an intrauterine fetal demise (Zaigham et al, Acta Obstet Gynecol Scand, 2020).
  1. In a systematic review of 6 reports of COVID-19 affecting 41 patients reported from China, (Dimascio et al, Am J Obstet Gynecol MFM, 2020).
  1. Findings out of 41 pregnancies with deliveries:
  1. Preterm delivery less than 37 weeks gestation: 41%
  2. Preterm birth less than 34 weeks gestation: 15% The background rate of preterm birth in China is 7%. The review did not clarify if the high preterm birth rate reflected spontaneous preterm labor or preterm birth due to medically-indicated deliveries.
  3. Perinatal death: 7%
  4. Preeclampsia: 13.6%
  5. Cesarean delivery: 91% This high rate of cesarean delivery may reflect the high background rate of cesarean delivery in China.
  1. Two New York hospitals published outcomes of 43 patients followed for a two week time period. (Breslin et al, Am J Obstet Gynecol MFM, 2020). These hospitals adopted a policy of routine testing for all women. Therefore rates of adverse events may be comparatively lower given the high number of asymptomatic women with COVID infection in the series.
  1. Findings out of 43 pregnancies, 18 deliveries:
  1. Preterm labor: 5% (1/18)
  2. Labor induction: 50% (9/18, mix of indications)
  3. Cesarean delivery: 44% (background cesarean rate not stated)
  4. No reports of preeclampsia, pregnancy loss or perinatal death

Fetal and Neonatal Outcomes

  1. The fetal course for COVID-19 is not fully elucidated, but other maternal respiratory illnesses and pyrexial infections are associated with worse fetal outcomes:
  1. Complications of other respiratory viral illnesses include preterm labor, premature rupture of membranes, intrauterine growth restriction, intrauterine fetal demise, neonatal death (Schwartz et al, Viruses, 2020).
  1. Increased rates of intrauterine growth restriction and intrauterine fetal demise have yet to be reported for COVID-19. However, these outcomes are biologically plausible in the setting of maternal inflammation, hypoxia, and pro-thrombotic state and warrant consideration in antenatal care.
  1. Fever in early pregnancy may be associated with an increased rate of birth defects, with neural tube defects being the most commonly described (Moretti et al, Epidemiology, 2005)
  2. Fever during labor may also be associated with neonatal risk, though distinguishing adverse outcomes due to noninfectious inflammation and intrauterine infection is challenging (Petrova et al, Obstet Gynecol, 2001)
  1. Vertical Transmission: Definitive evidence that SARS-CoV-2 crosses the placenta and infects the fetus is lacking; however, a few cases of possible in utero infection have been reported.
  1. Three of 33 infants born to mothers with COVID-19, developed early-onset infection. Amniotic fluid, cord blood, and breast milk, were negative for SARS-CoV-2 in these cases. Clinical symptoms from these infants infected with COVID-19 were mild and outcomes were favorable (Zeng et al, JAMA Pediatrics, 2020).
  2. In a US cohort of 18 infants tested for COVID-19 via SARS-Cov2-19 PCR nasoparyngeal swab all infants ultimately tested negative (Breslin et al, Am J Obstet Gynecol MFM, 2020).
  3. Reports of possible vertical transmission include a positive IgM in a neonate of a COVID-19 + mother at 2 hours of life without other exposure. The early time period of detection coupled with knowledge that IgM does not cross the placenta has called into question the possibility of vertical transmission in this case (Dong et al, JAMA, 2020).

Screening and Testing of Pregnant Women

  1. Identifying pregnant women with SARS-CoV-2 infection has several goals:
  1. To tailor frequency and location of prenatal care for identified COVID-19 positive women and COVID people under investigation (PUI)
  1. Whether or not an obstetric patient is seen for an in-person evaluation and the location of this evaluation should be based on a review of symptoms informing clinical suspicion for severe disease (Poon et al, Int Journal Obstet Gynaecol, 2020)
  2. At BWH pregnant patients with respiratory symptoms in the absence of obstetric complaints are first evaluated in the Emergency Department with fetal and obstetric evaluation for those with viable pregnancies facilitated by an obstetrics consult.
  1. To decrease risk of transmission to other patients, healthcare personnel, and family living in the same space
  2. To plan for labor and delivery care
  3. To plan for mother-infant separation strategies, if necessary
  1. Symptom Screening
  1. Symptom screening should be conducted over the phone before patient presents for care and again upon arrival at the facility of care
  2. All obstetric patients with symptoms should be considered COVID PUI and laboratory testing should be performed
  1. Laboratory Testing:
  1. World Health Organization guidelines recommend laboratory testing (qRT-PCR) for all suspected cases (i.e. symptomatic patients). Due to testing capacity issues, the Centers for Disease Control (CDC) recommends testing at provider’s discretion. Testing criteria vary by institution.
  2. Current BWH testing includes universal testing for patients being admitted to Labor and Delivery or those with a planned admission for scheduled induction of labor or cesarean delivery within the next 48 hours.
  3. Support persons of patients testing positive for SARS-CoV-2 should also be tested

Prenatal Care in the Setting of COVID-19

  1. Different models of prenatal care have been proposed to minimize exposures to patients (with and without COVID-19) and providers by decreasing frequency of in-person visits and ultrasounds. (SMFM Ultrasound Practice Suggestions).
  1. Selection depends on the resources available and provider discretion based on medical complexity
  1. BWH suggestions modify ACOG recommendations based on the needs of our high-risk patient population. (Boelig et al, Am J Obstet Gynecol MFM, 2020).
  1. Low Risk Patients: Low risk patients include patients without intermediate or high-risk obstetrical criteria. They should be asymptomatic (no pain or bleeding), without risk factors for ectopic pregnancy, and with low-risk aneuploidy screening.
  1. Dating scan with nuchal translucency at 11-13 weeks gestation coordinated with first OB visit
  2. Fetal survey at 19-20 weeks (favor 20 weeks with increasing BMI) coordinated with return OB visit
  3. For patients with a placenta previa or low-lying placenta on second trimester ultrasound repeat ultrasound for placental location at 32 weeks in the absence of bleeding.
  1. Intermediate Risk Patients: Hypertension not on medication, gestational diabetes or pregestational diabetes not on medication, advanced maternal age > 40 years old, BMI > 35, uncomplicated dichorionic diamniotic twin pregnancies, history of intrauterine growth restriction (IUGR) or preeclampsia in a prior pregnancy.
  1. Similar approach to first and second trimester screening as low risk patients.
  2. Ultrasound for estimated fetal weight at 30-32 weeks for those with a history of IUGR or preeclampsia in prior pregnancy. Repeat ultrasound every 6 weeks. Identification of IUGR places patient in high risk category.
  3. Dichorionic Twins: Ultrasound every 4 weeks for fetal growth beginning at 28 weeks.
  4. Diet-Controlled Pregestational Diabetes or Gestational Diabetes: Third trimester ultrasound for assessment of fetal weight at discretion of MD
  5. Fetal Anomalies: Growth surveillance tailored to fetal anomaly with more frequent surveillance in the face of hydrops, polyhydramnios, or concern for genetic syndrome.
  6. Short Cervix > 2.5 cm: Monitor cervical length every 2 weeks until 25 weeks if cervical length remains stable.
  1. High Risk Patients: Hypertension on medications, preeclampsia, gestational hypertension, pregestational or gestational diabetes on medications, IUGR in the current pregnancy, monochorionic twins and higher-order multiples, maternal renal disease, other complex maternal or fetal comorbidities.
  1. Similar approach to first and second trimester screening as low risk patients.
  2. Hypertension or Diabetes: Growth ultrasound every 6 weeks with weekly nonstress tests (NSTs) for interval fetal testing.
  3. Monochorionic Twins: Ultrasounds every 2 weeks to monitor for evidence of twin-to-twin transfusion syndrome.
  4. IUGR: Weekly NSTs with biophysical profile (BPP) and umbilical artery Doppler every 4 weeks in place of NST. Increase NSTs to twice weekly in the setting of abnormal Dopplers.
  5. Short Cervix < 2.5 cm before 25 Weeks: Weekly ultrasound for cervical length at the discretion of the OB care provider until 25 weeks. A final cervical length ultrasound can be considered after cerclage placement.

Prenatal Care for Patients with known COVID-19

  1. Given the theoretic concerns for adverse fetal outcomes, we recommend increased fetal surveillance for women with symptomatic COVID-19 infection
  1. Third trimester growth ultrasound surveillance at 28 weeks or time of diagnosis repeated every 3-4 weeks.
  2. Weekly fetal testing with nonstress test beginning at 32 weeks until delivery.
  3. Performance of biophysical profile in lieu of nonstress test at times of growth surveillance ultrasounds.
  1. To help conserve PPE and limit unnecessary precautions discontinuing isolation/infection precautions in patients with previously confirmed COVID-19 according to institutional policy is of paramount importance.

Labor and Delivery

Inpatient Antepartum Care for COVID-19 Positive and PUI

  1. Admission and Care Protocols:
  1. Patients known to be positive prior to arrival should be escorted by a member of the clinical staff from the main hospital entrance directly to a negative pressure room. They must wear an N-95 mask. In their rooms they may remove the mask in place of a surgical mask.
  2. Visitors will be limited to a single support person for all women admitted to Labor and Delivery. This support person should be the same individual for the duration of the hospitalization, and should remain in the room for the duration of the admission. Support persons are not allowed in the Labor and Delivery Triage area (an outpatient facility), the inpatient Antepartum floors, or in the operating room during cesarean delivery.
  3. Patients must identify a health care proxy and/or an advance directive on admission.
  4. Teams should designate one or two providers who will principally be involved in direct (in-person) patient care to minimize staff exposure
  1. Providers are encouraged to reduce the frequency of in-person assessment if clinically appropriate through use of ipad, telephone, headsets or other remote technologies
  1. PPE should be selected, donned and doffed per hospital policy (See PPE)
  1. The CDC does not categorize a vaginal delivery as an aerosolizing procedure; therefore droplet and contact precautions are deemed adequate (CDC FAQ)
  2. The Society for Maternal Fetal Medicine (SMFM) believes it is reasonable to consider N95 mask use for providers with significant and prolonged exposure given several variables unique to childbirth such as length of patient contact, repeated and prolonged exhalations, and substantial exposure to body fluids (SMFM and SOAP Labor and Delivery Considerations)
  1. Antenatal Corticosteroids and Tocolysis:
  1. The impact of exposure to corticosteroids on COVID-19 infection is uncertain (see systemic corticosteroids). How this applies to a short course of antenatal corticosteroids is not known. (SMFM and SOAP Labor and Delivery Considerations)
  2. BWH recommends following the guidance from the American College of Obstetricians and Gynecologists (ACOG) (ACOG FAQs for COVID):
  1. Given well-established benefit to neonates, use of antenatal betamethasone between 24+0 and 33+6 weeks of gestation in patients at high risk of preterm birth within seven days, and suspected or confirmed COVID-19 disease.
  2. Do not offer late preterm steroids for women between 34 0/7 weeks and 36 6/7 weeks of gestation
  3. These recommendations must be tailored to specific clinical circumstances, weighing the individualized risks and benefits to both neonates and mothers
  1. If antenatal corticosteroids are administered, tocolysis can be administered until completion.
  2. Magnesium Sulfate: Magnesium is routinely used for both fetal neuroprotection or preeclampsia/seizure prophylaxis, but carries some risks in the setting of COVID-19 infection:
  1. Benefits of therapy should be weighed against potential risks of maternal respiratory depression
  1. Respiratory depression typically occurs at levels of 10-13 mg/dL and will be preceded by loss of deep tendon reflexes often occurring at levels of 7-10 mg/dL.
  2. A single 4-gram bolus of magnesium sulfate without subsequent infusion may serve as an alternative to usual dosing in the setting of mild respiratory distress.
  1. If renal function is impaired, dose should be adjusted accordingly

Intrapartum Care for COVID-19 Positive and PUI

  1. Internal Monitors (Fetal Scalp Electrodes, Intrauterine Pressure Catheters):
  1. Limited data thus far do not suggest maternal-to-fetal transmission of SARS-CoV2 is likely to occur
  2. The use of this technology may provide more reliable monitoring limiting healthcare provider exposure for readjustment of monitors
  1. Amniotomy:
  1. Limited data do not suggest maternal-to-fetal transmission
  2. Amniotomy may still be utilized for labor management as clinically indicated (SMFM and SOAP Labor and Delivery Considerations)
  1. Labor Analgesia:
  1. Consider early epidural analgesia for labor to mitigate risks associated with general anesthesia in the setting of an emergent cesarean
  2. Avoid nitrous oxide due to risk of aerosolized infectious droplets
  3. Birthing pools will not be offered
  1. Mode of Delivery:
  1. Mode and timing of delivery should be individualized based on clinical status of the patient, gestational age, fetal condition. While COVID-19 itself is not an indication for delivery, elective delivery at 39 weeks can be considered given the uncertain impact of COVID-19 infection on fetal outcomes.
  2. Vaginal delivery is not contraindicated.
  3. Operative Delivery: Data on perinatal transmission at this time does not preclude the use of forceps or vacuum. An operative vaginal delivery may be considered to shorten the second stage since active pushing while wearing a surgical mask may be difficult for the patient
  4. Cesarean Delivery:
  1. Cesarean delivery should be performed in an operating room with negative pressure if the woman is suspected or confirmed to have COVID-19
  2. While regional and general anesthesia are both options, regional is preferable both for maternal benefit and prevention of exposure to staff given the aerosolizing nature of intubation.
  1. Cord Clamping: Do not delay cord clamping. There is insufficient evidence regarding whether delayed cord clamping increases the risk of infection to the newborn via direct contact (Poon et al, Int Journal Obstet Gynaecol, 2020)
  2. Post Delivery: Placental tissue, miscarried embryos/fetuses should be treated as infectious tissues and disposed of appropriately. Routine pathologic examination should be encouraged and if possible, testing of these tissues for SARS-CoV-2 by qRT-PCR should be undertaken.

Postpartum Care for COVID-19 Positive and PUI

  1. Postpartum Monitoring: Postpartum patients with COVID-19 should be evaluated for stability prior to transfer. This does not need to be an in person evaluation, but rather a “huddle” with the L&D nurse charged with giving passoff and the OB care provider. The patient’s disease state should be categorized and high-risk comorbidities identified (NIH Treatment Guidelines):
  1. Asymptomatic or Presymptomatic Infection: Individuals who test positive for SARS-CoV-2 but have no symptoms. Routine care unless comorbid risk factors for decompensation (i.e. preeclampsia, pulmonary disease other than mild intermittent asthma, immunosuppressed)
  2. Mild Illness: Individuals who have any of various signs and symptoms (e.g., fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnea, or abnormal imaging. Recommend Q4H vital signs and strict I&Os for first 24 hours for vaginal delivery and 48 hours for c-section.
  3. Moderate Illness: Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and SaO2 >93% on room air.Transfer to postpartum with continuous pulse oximetry monitoring for the first 24 hours or until improvement in presentation to mild disease (whichever takes longer). Plan for lab monitoring and additional imaging should be explicitly stated on transfer.
  4. Severe Illness: Individuals who have respiratory frequency > 30 breaths per minute, SaO2 ≤ 93% on room air, or lung infiltrates > 50%. Features of severe illness, heart rate > 120 beats per minute, oliguria with urine output < 30 cc/hr for 2 hours, or other clinical concern based on evaluation of the obstetric care provider remain on labor and delivery. If oxygen requirement is decreasing or stable after 24 hours consider transfer to postpartum with continuous O2 monitoring.
  1. Discharge and Follow Up: Patients with a history of mild illness should have a 1 week telehealth visit coordinated prior to discharge with their obstetric care provider. Patients with a history of moderate or severe disease should have a phone call from a healthcare provider (RN, CNM, PA, NP, MD) 48 hours after discharge and a 1 week dedicated telehealth visit coordinated after discharge. Patients with moderate to severe disease should also be offered VNA services for vital sign monitoring and anticoagulation teaching when indicated.

Breastfeeding

  1. Human milk helps provide protection to newborn infants against many illnesses during early life and is the best source of nutrition for most infants. A limited number of studies suggest that SARS CoV-2, the virus that causes COVID-19, is not detectable in the human milk of mothers with COVID-19 (Chen et al, Lancet, 2020).
  1. The CDC, WHO, and AAP suggest that the benefits of breastfeeding in the setting of COVID-19 appear to outweigh the potential risks of viral transmission from mother to infant.
  1. The following are recommended strategies for the breastfeeding mother-infant dyad with COVID-19:
  1. Mothers are encouraged to practice excellent hand hygiene and pump their breasts following birth to initiate lactogenesis.
  1. A dedicated breast pump should be made available to each woman during the postpartum hospitalization.
  2. Breast pumps and components should be thoroughly cleaned in between pumping sessions using standard policies that must include cleaning the pump with disinfectant wipes and washing pump attachments with hot soapy water.
  1. Infants should be fed pumped milk by a healthy caregiver during the hospitalization and until the mother is recovered from her COVID-19 illness.
  1. Recovery from COVID-19 illness is defined as at least 72 hours since resolution of symptoms of COVID and at least 7 days from when her illness began.
  1. Mothers who wish to breastfeed directly are encouraged to practice excellent hand hygiene and wear a surgical mask during breastfeeding.

Pregnant Patients Presenting with COVID-19

Mild Illness

  1. For patients with no known comorbidities or respiratory symptoms (Poon et al, Int Journal Obstet Gynaecol, 2020)
  1. Ensure patient comes in for COVID-19 testing, concurrent testing for influenza/ RSV, and vital sign check
  1. If patient has normal vital signs, no difficulty breathing or shortness of breath, no clinical indication for imaging or treatment, and is able to follow up with care then the patient can be managed at home (ACOG and SMFM, Outpatient Assessment and Management)
  2. If any of these is not the case the patient should be referred to the Emergency Department for evaluation (see “moderate” disease below). For patients with symptoms and with medical comorbidities (e.g., hypertension, diabetes, asthma, HIV) a lower threshold should be used.
  1. Treatment for mild illness is symptomatic.
  1. Use pregnancy-approved medications such as acetaminophen and cough suppressants.
  2. There is currently no antiviral treatment recommended for mild cases of COVID-19 ·
  3. Fever may be associated with an increased rate of birth defects, especially neural tube defects, so we recommend the use of acetaminophen for pregnant women with a temperature ≥ 100.40F
  4. Maintain adequate hydration
  1. Patient should self-isolate in the home (e.g., separate bedroom, appropriate caregivers available at home, access to food and other necessities)
  2. A reliable system should be implemented for healthcare providers to check-in on symptoms with a phone call 48 hours after evaluation and a telehealth visit 7-10 days after initial evaluation.
  3. Patients should be instructed to return to care if they develop:
  1. Worsening dyspnea at rest or with ambulation
  2. Inability to tolerate oral hydration
  3. Hemoptysis
  4. Chest pain/pressure
  5. Dizziness
  6. Obstetric complaints

Moderate or Severe Illness

  1. Decision to admit:
  1. Pregnant women, due to both younger age and physiologic adaptation, have a remarkable ability to compensate for medical illness in a way that masks its severity until their hemodynamic reserves are suddenly exhausted. Classically, they will appear quite well until they rapidly deteriorate.
  2. Any pregnant patient with respiratory symptoms should be observed or admitted as an inpatient for a 48-hour period. Suggested criteria for observation or admission include:
  1. SaO2 < 95% on room air. Oxygenation targets are in the pregnant population compared to the 93% accepted in the general population due to need for fetal perfusion. Please obtain ambulatory saturations as well.
  2. Respiratory rate > 30
  3. Maternal tachycardia > 120 not improved with fluids
  4. Blood pressure abnormalities;
  1. Hypotension with systolic blood pressure < 90 or diastolic blood pressure < 50 (unless baseline blood pressure below these criteria based on review of prenatal record)
  2. Hypertension defined by systolic blood pressure > 140 or diastolic blood pressure > 90 on two separate measurements at reasonably spaced intervals in the absence of chronic hypertension
  1. Persistent fever > 101°F despite antipyretic
  2. Lab abnormalities including transaminitis, elevated creatinine, or new thrombocytopenia < 150K
  3. Headache not resolved by medications without other explanation (given risk for preeclampsia)
  4. Unexplained abdominal pain
  5. Category 2 fetal heart rate tracing despite adequate maternal resuscitation
  6. Obstetric complaints (includes the presence of contractions, leakage of fluid, vaginal bleeding, or decreased fetal movement)
  1. Patients with even mild disease may warrant admission for obstetric indications independent of severity
  1. The presence of maternal or fetal comorbidities
  1. Maternal examples include asthma or pulmonary disease, HIV infection, or hypertension including preeclampsia.
  2. Fetal examples include intrauterine growth restriction, monochorionic twin pregnancy, or other markers of placental insufficiency.
  1. If admitting, the appropriate admission location (i.e. medical ward, labor and delivery, or intensive care unit) should be made in conjunction with the obstetric care team.
  2. Inpatient diagnosis and management:
  1. Management is the same as for the nonpregnant patient with rare exceptions.
  2. Routine pharmacologic DVT prophylaxis is warranted
  3. Suggested diagnostic and therapeutic orders for pregnant patients can be found here.
  1. Most medications are safe in pregnancy and breastfeeding. NSAIDs, fluoroquinolones, and doxycycline should be avoided if possible. Medication guidelines specific to COVID in pregnancy can be found below.
  1. Indications for ICU transfer:
  1. A low threshold for evaluation is encouraged and suggested criteria include:
  1. Increased work of breathing
  2. Increasing tachypnea
  3. Hypoxia requiring 6L nasal cannula
  4. PCO2 > 40 or pH < 7.35
  5. Hypotension or oliguria despite adequate fluids
  6. Chest pain, worsening tachycardia, or arrhythmia other than sinus tachycardia
  7. Altered mental status
  1. Discharge considerations: Discharge planning for patients admitted with manifestations of COVID-19 mirrors that of the general population with a few notable additions:
  1. Arrange for follow up with her obstetric care provider within the first 48 hours and then within a week to assess for evolution of symptoms and consider repeat testing for removal from precautions.
  2. Ensure the patient has the requisite resources to access the hospital system prior to discharge (i.e. transportation, access to emergency services in a language spoken by the patient, clear instructions to re-engage accessible to the patient based on her level of health literacy).

Critical Illness

  1. Modifications from the standard of care should be to support the physiology of pregnancy and optimize maternal (and therefore fetal) hemodynamics.
  1. Care should be undertaken as a part of a collaborative multidisciplinary team including the ICU team, the obstetrics team, and consultants in the location that makes the most sense based on the patient’s anticipated clinical needs. For patients with active obstetric issues that outweigh their critical care needs the possibility of providing some components of critical care on labor and delivery (such as vasopressor support or hemodynamic monitoring) should be considered due to the close proximity to the operating room.
  2. Pathways for communication with obstetrics and contingencies for notification should be clearly outlined and readily available to the primary team.
  1. Hallmark physiologic changes of pregnancy include:
  1. Increased cardiac output (heart rate and stroke volume)
  2. Decreased systemic vascular resistance
  3. Increased minute ventilation (driven by respiratory rate)
  4. Physiologic compensated respiratory alkalosis
  5. Increased GFR and volume of distribution
  6. Expanded plasma volume
  7. Alterations in clotting cascade to promote coagulation
  1. The majority of management of the critically-ill pregnant patient is unchanged from that of the general population
  1. These are quick tips for intensivists caring for critically ill obstetric patients.
  2. Intubation should be considered early given increased airway edema and aspiration risk in pregnancy as well as limited functional residual capacity.
  3. Ventilation should target the respiratory alkalosis of pregnancy maintaining a pCO2 < 45 and a pH > 7.35.
  1. Permissive hypercapnea may be acceptable but inability to maintain these targets alongside other standards of care for lung-protective ventilation should prompt a discussion with the obstetric care team.
  2. Depending on the gestational age and clinical status this may prompt more liberal parameters, additional fetal monitoring, or consideration of delivery.
  1. Prone positioning in pregnancy has been reported and should be considered for standard indications (Dennis et al, BMC Pregnancy Childbirth, 2018). Early discussion of the feasibility of this strategy and gestational-age dependent patient positioning considerations should take place with the obstetric team.
  1. Fetal outcomes vary according to gestational age. The obstetrics team should share anticipated outcomes at a given gestational age with the critical care team to inform their clinical decision-making and management.
  1. Antenatal Corticosteroids: Antenatal corticosteroids are typically given as betamethasone 12 mg IM Q24 hours for two doses which is the equivalent of 60 mg methylprednisolone. Importantly, methylprednisolone and prednisone are metabolized by the placenta making the administration of betamethasone or dexamethasone necessary to impact fetal lung maturity.
  2. Magnesium: Theoretic respiratory depression is less concerning in an intubated patient population. The additional benefit of magnesium for seizure prophylaxis in addition to medications used for sedation is uncertain.
  3. Tocolysis: Tocolysis is not contraindicated in critical illness but should be individualized based on maternal status, gestational age, and risk of progression of preterm labor. The fetal risks of slowing spontaneous preterm labor in a critically ill patient with the potential for comorbid intrauterine infection as well as the maternal side effects of the individual agents should be balanced with the gestational-age dependent fetal benefit.
  1. Data associating NSAIDs to adverse outcomes in COVID-19 infection is inconsistent but warrants caution in those with limited clinical reserve.
  2. Immediate-release nifedipine is a potent systemic and pulmonary vasodilator which can worsen hypotension or VQ mismatch. Nifedipine is contraindicated for women with cardiac manifestations of the disease.
  1. Rates of spontaneous preterm birth in the critically-ill population are high.
  1. Unexplained maternal tachycardia, hypertension, increasing sedation requirements, and tachypnea should prompt a call to the obstetric care team for evaluation for possible preterm labor.
  2. Contraindications to labor (i.e. placenta previa, nonvertex presentation, prior uterine surgery) should be noted and incorporated into the checklist outlining considerations for vaginal delivery.
  1. A plan for fetal monitoring should be clearly communicated and facilitated by members of the obstetric team.
  1. For critically-ill patients twice daily nonstress tests should be considered both to monitor fetal status and assess maternal hemodynamics.
  2. Any change in clinical status should prompt consideration of fetal assessment balancing gestational age,
  1. Neonatology should be notified of any pregnant patient admitted to the hospital at or beyond 22 weeks to offer a consultation when appropriate and for situational awareness.
  1. Delivery planning is an essential part of every admission
  1. A vaginal delivery kit, cesarean delivery kit, and neonatal warmer and resuscitation kit should be at the bedside in anticipation of spontaneous delivery or maternal cardiac arrest for all patients.
  2. A discussion of the pathway for emergent delivery for fetal indications (STAT c-section) including the location of delivery, transport process, and involved personnel should take place and account for gestational age and maternal stability.
  1. The BWH-specific protocol should be displayed in a visible location and members of the care team should be familiar with its use.
  1. Delivery may become necessary in select circumstances where oxygenation or ventilation are thought to be impaired by pregnancy.
  1. Anticipate the autotransfusion after delivery as blood returns from the uterus into the circulation. Diuresis, PEEP optimization, and judicious use of alveolar recruitment maneuvers may be needed.
  2. Vaginal delivery is the preferred mode of delivery for patients in the absence of contraindication to labor. The decision for vaginal versus cesarean delivery in the critically-ill patient should be individualized taking into account parity, gestational age, monitoring needs, and a priori likelihood of a successful vaginal birth.
  1. Maternal cardiac arrest at or beyond 20 weeks, or when the uterus is at the level of the umbilicus, includes specific modifications to account for the impact of the gravid uterus (Jeejeebhoy et al, Circulation, 2015).
  1. Provide immediate left uterine displacement by either pushing or pulling the uterus off the IVC.
  1. This is a dedicated role for a member of the code team.
  1. Ensure the IV used for code medications is above the level of the diaphragm to ensure no interference with return to circulation
  2. Remove and detach all fetal monitor.
  3. Prepare to begin a resuscitative hysterotomy (i.e. cesarean delivery) by 4 minutes without return of spontaneous circulation (ROSC) with goal for delivery of the fetus by 5 minutes in an attempt to restore ROSC

Therapeutics in Pregnancy

Antipyretics

  1. Acetaminophen:
  1. Acetaminophen is the preferred antipyretic for COVID-19. It is also the preferred antipyretic for influenza in pregnancy (ACOG Guidance on the Assessment and Treatment of Pregnant Women with Suspected or Confirmed Influenza; SMFM, Am J Obstet Gynecol, 2017).
  2. While some epidemiologic studies raised the possibility of an association between in utero acetaminophen exposure and the risk of ADHD in later life (Masarwa R et al, Am J Epidemiol, 2018), data review by the US FDA and the Society for Maternal Fetal Medicine found these data to be inconclusive (FDA safety communication, US FDA, 2015; SMFM Am J Obstet Gynecol, 2017).
  3. The recommended dose of acetaminophen for pregnant women is the same as the recommended dose in adults: up to 1,000 mg in a single dose, not-to-exceed 3,000 mg in a 24-hour period.
  1. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
  1. See NSAID section in the therapeutics chapter.
  2. NSAIDs are generally avoided as first line agents for management of fever or pain in pregnancy due to inconclusive data regarding first trimester risk, and risk of premature closure of the ductus arteriosus in later pregnancy.
  1. Aspirin
  1. Low-dose aspirin is used in pregnancy for several indications, most commonly in preventing preeclampsia (ACOG Guidance on Low-Dose Aspirin Use During Pregnancy) We support continued use of low-dose aspirin after discussion with maternal-fetal-medicine and other relevant consultative services (e.g. cardiology)
  2. We recommend against using moderate or high dose aspirin as an antipyretic

Experimental Antiviral Agents for COVID-19 in Pregnancy

  1. Treatment for COVID-19 is evolving rapidly. The BWH infectious diseases COVID-19 treatment guidelines (Partners login required), Infectious Diseases, and Maternal Fetal Medicine consultations take precedence over the information provided in the sections below. For all the agents below please refer to the Therapeutics chapter
  2. Hydroxychloroquine
  1. HCQ Use in Pregnancy
  1. HCQ crosses the placenta
  2. HCQ is considered safe to continue for the management of rheumatologic diseases, such as systemic lupus erythematosus (SLE), in pregnancy
  3. Several studies of women in whom HCQ therapy was continued in pregnancy revealed no adverse fetal outcomes (Parke, J Rheumatol, 1996; Clowse et al, Arthritis Rheum, 2006, Costedoat-Chalumeau, Arthritis Rheum, 2003)
  1. HCQ Use in Lactation
  1. HCQ levels in breastmilk are low and it’s considered safe to use in lactating mothers.
  1. Evidence for HCQ for COVID-19 in Pregnancy
  1. HCQ is an investigational agent for the treatment of COVID-19 and has not yet been demonstrated to be effective. In a case series of 43 patients treated at two New York City Columbia University hospitals, 29 were symptomatic at presentation, and two received HCQ, one antepartum and the other postpartum, Both women had severe disease, received a higher loading dose than the BWH recommended dose (600 mg orally every 12 hours on day one, followed by 400 mg daily for 4 additional days). Outcomes are not available for these women (Breslin et al, Am J Obstet Gynecol MFM, 2020)
  1. Recommendations
  1. In consultation with the Infectious Diseases and Maternal Fetal Medicine consult services, HCQ may be used for the treatment of inpatient pregnant and lactating women who:
  1. are not candidates for clinical trials
  2. have indicators of moderate to severe disease, or other risk factors for progression
  1. We do not routinely recommend the use of azithromycin with HCQ for the indication of COVID-19 (see Azithromycin)
  2. Per our treatment guidelines, dosing of HCQ for pregnant inpatients is the same as for non-pregnant adults (see Hydroxychloroquine)
  1. Remdesivir
  1. Remdesivir is an investigational agent. Pregnancy is an exclusion for participation in trials NCT04292730 and NCT04292899. It is available for pregnant women with confirmed COVID-19 infection and severe manifestation of the disease through an individual compassionate emergency use access program offered by Gilead Sciences.
  1. The Infectious Diseases and Maternal Fetal Medicine consult services should be involved in all decisions to apply for compassionate use.
  1. Application and contact information can be found in our treatment guidelines (partners login required).
  2. Providers outside the BWH may fill a Gilead online application
  1. Remdesivir in Pregnancy
  1. Remdesivir has not yet been studied in pregnant women. A few pregnant women with Ebola virus infection have received remdesivir through clinical trials (Mulangu S et al, NEJM, 2019)
  1. Immunomodulators
  1. Anti-IL6 Agents (Tocilizumab, Siltuximab, Sarilumab)
  1. See Therapeutics chapter summary for anti-IL-6 agents
  1. We do not recommend the routine use of anti-IL-6 agents in COVID-19 or in pregnancy unless part of a clinical trial
  1. Tocilizumab in Pregnancy
  1. Tocilizumab crosses the placenta
  2. Post-marketing data analysis of pregnancy outcomes in 288 evaluable women out of 399 who were exposed to tocilizumab shortly before or during pregnancy revealed no substantial increase in adverse pregnancy outcomes. However, this series is too small and diverse to demonstrate the safety of this agent in pregnancy (Hoeltzenbein M et al. Semin Arthritis Rheum, 2016)
  3. Outcome data during pregnancy are limited
  1. Tocilizumab may only be considered for use in pregnant women who have severe or critical COVID-19 AND suspicion of cytokine activation syndrome with elevated IL-6 levels in conjunction with Infectious Diseases consultation
  1. Systemic Corticosteroids
  1. See Systemic Corticosteroids
  2. We do not recommend the routine use of systemic corticosteroids for COVID-19 except as part of a clinical trial or if treating another indication
  3. There are no data to inform on the risks and benefits of the use of steroids for fetal maturation in women with suspected or confirmed COVID-19 (see above)
  1. Systemic Antibiotics
  1. Information on treatment of bacterial infections that may be associated with COVID-19 can be found in the Infectious Disease chapter
  2. There is no sufficient supporting evidence to recommend the use azithromycin in combination with hydroxychloroquine for the indication of COVID-19 treatment
  1. Concomitant treatment of community-acquired bacterial pneumonia, if suspected, and typical coverage is desired, should be considered with an infectious diseases consultation, after weighing cardiac risks and benefits
  1. Suspected or confirmed COVID-19 should not delay treatment with antibiotics that would usually be given for a non-COVID-19 indication (for example treatment of bacteriuria, or evaluation or treatment of fever with prolonged rupture of membranes or postpartum fever)