key: cord-0755104-6qn3ihgh
authors: Rose, Carl H.; Wyatt, Michelle A.; Narang, Kavita; Lorenz, Kathleen E.; Szymanski, Linda M.; Vaught, Arthur J.
title: Timing of delivery with COVID-19 pneumonia requiring intensive care unit admission
date: 2021-04-06
journal: Am J Obstet Gynecol MFM
DOI: 10.1016/j.ajogmf.2021.100373
sha: a6390ea38ba0d0fb15e65bd62e523d741886d613
doc_id: 755104
cord_uid: 6qn3ihgh

Approximately 4% of pregnant patients with COVID-19 infection require intensive care unit admission. Given the practical implications of advanced ventilatory and circulatory support techniques, urgent or emergent delivery for non-reassuring fetal status frequently represents a logistical impossibility. This manuscript proposes a protocol for obstetrical management of patients in these situations, emphasizing coordinated preparation between obstetric, anesthesiology, and intensivist teams, with planned preterm delivery at gestational ages when neonatal outcomes are likely to be favorable.

Approximately 13% of pregnant patients who contract COVID-19 infection present or progress to severe disease, with 4% requiring ICU admission [ Table 1 ]. [1] [2] [3] [4] The Centers for Disease Control and Prevention (CDC) has suggested pregnancy confers a higher risk of requiring either mechanical ventilation and/or ECMO; overall mortality appears to be increased, and limited contemporary data has suggested a higher rate of intrauterine fetal demise. 5, 6 Fortunately the majority of pregnant patients with COVID-19 infection experience mild symptomatology and do not require hospitalization, and many of these patients do not come to the attention of healthcare providers beyond reporting positive test results, confirmation of stable clinical status, and recommendation for self-quarantine. 3 However for patients who do require supplemental oxygen, mechanical ventilation, or ECMO, there is growing recognition that recovery and eventual extubation (and/or decannulation) is not uncommonly a very protracted process. 7 Thus the obstetrician may be confronted with a situation where delivery may either be performed electively in a controlled manner prior to escalation (or expected escalation) of therapy, or due to inherent practical limitations, will not be feasible until maternal cardiopulmonary stability has been stabilized.

Most of the contemporary literature regarding obstetric COVID-19 falls into the realm of either epidemiologic reports describing maternal and neonatal outcomes or case reports describing management in a variety of clinical circumstances. 8, 9 Preliminary data from China suggested that preterm delivery via cesarean section was almost three-fold more common in COVID-19-infected patients, although specific distinction into indicated or spontaneous subcategories was not reported. 10 Subsequent metanalysis has shown an overall preterm delivery rate of approximately 29%, while another group found a cesarean delivery rate of 89%. 11, 12 Early data from the United States has demonstrated a lower but overall increased (15%) incidence of preterm delivery, with a concomitant increase in cesarean section rate (38%), while more recent reviews focusing exclusively on the criticallyill population have found an 88% rate of preterm delivery with 94% occurring via cesarean section. 6, 13 An expert consensus panel has recommended delivery for patients with severe disease at ≥32-34 weeks due to anticipated high likelihood of intact neonatal survival. 14, 15 Neonatal Outcomes of neonates born to mothers with COVID-19 infection are primarily dependent on gestational age at birth. 16 Although isolated reports have described rare individual cases of vertical transmission, the overall incidence of postnatal infection is reported to fall in the range of 3-5%; given the relatively recent onset of the pandemic long-term data is not yet available. [17] [18] [19] Most neonatal complications arise as a result of iatrogenic prematurity, rather than the infection itself.

Pregnant patients admitted to the ICU constitute a relatively unique population, in that both maternal and fetal status must simultaneously be taken into account. Guidelines for management are primarily derived from clinical experience -not clinical trials -and tend to focus on treatment of the maternal condition, with only general recommendations regarding fetal assessment and indications for delivery. 20 With respect to COVID-19 pneumonia, principles of care are most similar to patients with acute respiratory distress syndrome (ARDS), with modifications in medication regimens, target laboratory and physiologic parameters, and maternal positioning. 21 Decisions regarding frequency of fetal monitoring and/or delivery are governed by maternal status and gestational age, with the fetal cardiotocograph proposed to represent an additional "vital sign" to both guide and determine efficacy of therapy. 22 Criteria for refractory maternal hypoxemia generally include a PaO 2 <60 mmHg while receiving an FIO 2 of 1.0, however on a clinical basis this definition can be expanded to include severe hypoxemia (PaO 2 /FIO 2 ratio < 150) unresponsive to incremental increases in positive end expiratory pressure (PEEP), recruitment of lung volumes, prone positioning, and/or deep sedation with chemical paralysis. 23 Advanced therapies such as pulmonary vasodilator medications or veno-venous (V-V) ECMO are often considered in these situations, although complications of hemorrhage requiring transfusion (57-67%) and infection (58%) are frequent with ECMO, while the requirement for continuous anticoagulation introduces a further complicating factor in the event of unplanned delivery. [24] [25] [26] When a pregnant patient with COVID-19 pneumonia is admitted to the ICU, parameters for urgent delivery should be established and a contingency plan communicated amongst all involved teams. Often there are substantial practical impediments involved in rapidly moving a critically-ill patient from the ICU to a delivery suite or operating room, particularly if located in geographically separate areas of a hospital; consequently the ability to respond to a non-reassuring fetal heart rate pattern by performing an "emergent" cesarean section in the conventional obstetrical manner may become a logistical impossibility. Moreover, the actual process of transporting a patient with COVID-19 exposes additional personnel to infectious risk. Proceeding with delivery in the ICU represents an alternative, however this also may present attendant difficulties due to surgical staff unfamiliarity with an unconventional setting and ability to expediently and efficiently manage intraoperative complications (i.e. postpartum hemorrhage, etc.); at the primary author's institution this would generally be reserved for circumstances of perimortem/resuscitative cesarean delivery.

Recognizing that admission to the ICU for COVID-19 pneumonia does not constitute an intrinsic indication for delivery per se, for clinically stable patients at gestational ages 23/24-32 weeks continuation of pregnancy with intermittent monitoring of the fetal heart rate represents the preferred approach. If possible, the patient or responsible family members should be engaged to ascertain their preferences for delivery and neonatal resuscitation; Neonatology consultation may be advantageous in counseling. If refractory maternal hypoxemia results in non-reassuring fetal status, maternal interventions should be trialed for defined interval, balancing risk of potential neonatal acidosis with (indicated) iatrogenic premature delivery.

To preclude such a scenario, given anticipated favorable neonatal outcomes, the authors would suggest in pregnant patients requiring advanced oxygen delivery modalities (mechanical ventilation with PEEP ≥10cm H 2 O or V-V ECMO), elective delivery be considered at gestational ages of 32 0/7-33 6/7 weeks, particularly if a course of antenatal corticosteroids has been completed. If a patient stabilizes with escalated oxygen therapy, delivery should be considered once a course of antenatal corticosteroids has been administered, however if maternal oxygenation does not improve with escalating support expedient delivery -irrespective of completion of antenatal corticosteroid course -is recommended.

This would be similarly applicable for patients at gestational ages of ≥34 0/7 weeks; as antenatal corticosteroids are not recommended with COVID-19 infection in the late preterm period, delivery should be considered once maternal status is optimized.

Method of delivery can be individualized based on maternal clinical status, fetal condition, and obstetrical history. Successful induction of labor for mechanically-ventilated COVID-19 patients has been described, although non-reassuring fetal status has been reported intrapartum in 34% of pregnancies in an early systematic review; consequently for coordination of necessary resources and personnel availability, cesarean delivery may represent the most pragmatic option. 27, 28 Interestingly, a single case report described marked pulmonary improvement following cesarean section in a COVID-19 patient at 30 5/7 weeks, suggesting mechanical relief of the reduction in functional residual capacity and residual volume imposed by the gravid uterus may confer a therapeutic benefit; this may also be true with concurrent maternal respiratory conditions such as asthma and/or obesity which alter lung volumes. 29 Postpartum improvement in hepatic disease has also been reported. 30 However objective maternal benefit from delivery remains largely conjectural at this time, and is likely to remain so secondary to the inability to conduct clinical trials in this specific population.

The primary risks of elective preterm delivery include iatrogenic prematurity in the neonate and subjecting a critically-ill hypoxemic patient to further labor and/or surgical stress in the context of an uncertain prognosis. As noted, inherently the majority of deliveries in these circumstances are via cesarean section, and at the current time there is no evidence that route of delivery adversely influences maternal prognosis.

Accordingly, based on the authors' combined institutional experiences, we would propose the following general guideline for pregnant patients requiring ICU admission for COVID-19 pneumonia [ Figure 1 ]:

 Obtain group B streptococcal culture if antibiotics have not been previously started.

 Prophylactic anticoagulation with unfractionated heparin. 31  Administration of remdesivir, dexamethasone, and/or other FDA-approved therapeutics per institutional protocols; if dexamethasone is elected, a combination protocol of 48 hours of dexamethasone (6mg intramuscular every 12 hours for 4 doses) followed by methylprednisolone (32mg daily in single or divided doses) to complete a 10-day course would limit fetal corticosteroid exposure. 32  Obstetrical ultrasound to confirm fetal viability and gestational age (previable); gestational age, fetal presentation, estimated fetal weight, and amniotic fluid volume (viable).

 Interval auscultation of fetal heart rate (every 1-7 days, contingent on provider preference), with repeat assessment if maternal clinical status deteriorates.

 Delivery at these previable gestational ages would only be indicated in the event of maternal cardiopulmonary arrest at gestational age ≥20 weeks (resuscitative cesarean delivery).

 Administration of an initial course of antenatal corticosteroids; a repeat course may be given if ≥7 days have elapsed and delivery in the next 7 days is deemed probable. 33  Daily fetal assessment in the setting of stable maternal clinical status and oxygen requirements;

convert to continuous fetal monitoring if maternal condition becomes unstable.  Omit course of antenatal corticosteroids. 35 Neonatology with consideration of planned delivery following maternal stabilization. o Cognizant that fetal status is inherently reflective of maternal, consider obtaining matched maternal arterial and fetal umbilical artery blood gas values at time of delivery for comparative purposes. 34 As the COVID-19 epidemic continues to besiege intensive care units nationwide, the authors recognize this protocol is based primarily on limits of existing data and collective personal experience. The fundamental intent is to provide an initial blueprint for individual institutions to modify based on specific facilities, personnel, and circumstances, and is anticipated to evolve with introduction of new therapies. 

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