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Oxygen saturation in pregnant individuals with COVID-19: time for re-appraisal?

Published:December 16, 2021DOI:https://doi.org/10.1016/j.ajog.2021.12.023
      Managing pregnant individuals with acute respiratory disease secondary to COVID-19 has been a challenge. Most professional societies including the Society for Maternal-Fetal Medicine recommend keeping O2 saturation at ≥95% in pregnant individuals. Reaching this target has been increasingly difficult in some patients, especially during the latest wave of infections attributed to the delta variant of SARS-CoV-2. In the absence of adequate supporting data, and in the setting of a reassuring fetal status, we propose that maternal O2 saturation should be maintained between 92% and 96% for admitted patients with acute respiratory failure who require supplemental O2. This may prevent unnecessary invasive interventions that might not hold maternal or fetal benefit, specifically at very preterm gestational ages.

      Key words

      Introduction and Current Guidelines

      During pregnancy, several professional societies recommend maintaining O2 saturation (SpO2) at ≥95%.
      Society for Maternal-Fetal Medicine
      Management considerations for pregnant patients with COVID-19.
      Royal College of Obstetricians and Gynaecologists
      Coronavirus (COVID-19) infection in pregnancy.
      • Poon L.C.
      • Yang H.
      • Kapur A.
      • et al.
      Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: information for healthcare professionals.
      In response to the current COVID-19 pandemic, the Society for Maternal-Fetal Medicine (SMFM) recommends that the target SpO2 for pregnant individuals should be higher than recommended for the nonpregnant population (SpO2≥92%). Furthermore, they recommend that inpatient monitoring should be considered for pregnant individuals with moderate or severe signs or symptoms of COVID-19 and for those whose SpO2 drop below 95% while on room air during exertion. These patients should call their healthcare provider, undergo prompt evaluation, and be considered for inpatient admission, because they may require admission to higher level of care units such as an intensive care unit or a step-down unit.
      Society for Maternal-Fetal Medicine
      Management considerations for pregnant patients with COVID-19.
      Other professional societies such as the Royal College of Obstetricians and Gynaecologists and the International Federation of Gynecology and Obstetrics have advocated for the maintenance of SpO2 at a similar cutoff of ≥95%.
      Royal College of Obstetricians and Gynaecologists
      Coronavirus (COVID-19) infection in pregnancy.
      ,
      • Poon L.C.
      • Yang H.
      • Kapur A.
      • et al.
      Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: information for healthcare professionals.
      However, the evidence supporting maintenance of SpO2 at this cutoff is limited. Meanwhile, the World Health Organization suggests maintaining SpO2 at 92% to 95% in pregnant individuals with severe respiratory infection secondary to COVID-19.
      World Health Organization
      Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) is suspected.

      What is the Evidence Behind Using an O2 Saturation of ≥95%?

      There are no published trials or clinical studies demonstrating that an SpO2 at or above 95% is necessary for pregnant individuals to maintain adequate fetal oxygenation. Expert opinions suggest initiating supplemental O2 for pregnant individuals when their SpO2 falls below 94%, and this is based on known physiological changes that occur during pregnancy such as an increase in the partial pressure of O2 (PaO2) and increased O2 demand.
      • Pacheco L.D.
      • Saad A.F.
      • Saade G.
      Early acute respiratory support for pregnant patients with coronavirus disease 2019 (COVID-19) infection.
      Some of the current guidelines that suggest maintaining an SpO2 of ≥95%
      • Poon L.C.
      • Yang H.
      • Kapur A.
      • et al.
      Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: information for healthcare professionals.
      ,
      • Chen D.
      • Yang H.
      • Cao Y.
      • et al.
      Expert consensus for managing pregnant women and neonates born to mothers with suspected or confirmed novel coronavirus (COVID-19) infection.
      ,
      • Poon L.C.
      • Yang H.
      • Dumont S.
      • et al.
      ISUOG Interim Guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium: information for healthcare professionals - an update.
      cite a paper published by Bhatia et al.
      • Bhatia P.K.
      • Biyani G.
      • Mohammed S.
      • Sethi P.
      • Bihani P.
      Acute respiratory failure and mechanical ventilation in pregnant patient: a narrative review of literature.
      These authors state that a PaO2 of 70 mm Hg is required to maintain adequate fetal oxygenation, which they also associate with a maternal SpO2 of 95%.
      • Bhatia P.K.
      • Biyani G.
      • Mohammed S.
      • Sethi P.
      • Bihani P.
      Acute respiratory failure and mechanical ventilation in pregnant patient: a narrative review of literature.
      Bhatia et al
      • Bhatia P.K.
      • Biyani G.
      • Mohammed S.
      • Sethi P.
      • Bihani P.
      Acute respiratory failure and mechanical ventilation in pregnant patient: a narrative review of literature.
      make this conclusion on the basis of a study by Catanzarite et al
      • Catanzarite V.
      • Willms D.
      • Wong D.
      • Landers C.
      • Cousins L.
      • Schrimmer D.
      Acute respiratory distress syndrome in pregnancy and the puerperium: causes, courses, and outcomes.
      who included 28 women with acute respiratory distress syndrome (ARDS) who required intubation during pregnancy or within 1 week postpartum.
      • Catanzarite V.
      • Willms D.
      • Wong D.
      • Landers C.
      • Cousins L.
      • Schrimmer D.
      Acute respiratory distress syndrome in pregnancy and the puerperium: causes, courses, and outcomes.
      This study is limited because it used the older definition of ARDS, included patients only if they were intubated and within 7 days of delivery, and used the birth outcome of perinatal asphyxia, on the basis of historic data, to indicate a causal mechanism of neonatal hypoxia.
      • Catanzarite V.
      • Willms D.
      • Wong D.
      • Landers C.
      • Cousins L.
      • Schrimmer D.
      Acute respiratory distress syndrome in pregnancy and the puerperium: causes, courses, and outcomes.
      Applying these data to modern guidelines ignores >20 years of progress that has been made in the management of ARDS and confounding conditions such as the high rate of maternal multisystem organ failure. Although evidence from severe acute respiratory syndrome and COVID-19 suggests that there is a higher rate of fetal growth restriction in cases with severe maternal illness,
      • Dashraath P.
      • Wong J.L.J.
      • Lim M.X.K.
      • et al.
      Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.
      • Di Mascio D.
      • Khalil A.
      • Saccone G.
      • et al.
      Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.
      • Wong S.F.
      • Chow K.M.
      • Leung T.N.
      • et al.
      Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome.
      this is likely multifactorial instead of being limited to hypoxemia as the cause. There is no compelling objective evidence that an SpO2 of 95% is required for adequate fetal oxygenation.
      Mallampali et al
      • Mallampalli A.
      • Powner D.J.
      • Gardner M.O.
      Cardiopulmonary resuscitation and somatic support of the pregnant patient.
      recommend maintaining the maternal PaO2 above 60 to 70 mm Hg to avoid adverse effects on uteroplacental perfusion. However, other experts suggest that a PaO2 of >60 mm Hg (correlating with an SpO2 of >90%) is a reasonable target for pregnant individuals with acute respiratory failure.
      • Wong S.F.
      • Chow K.M.
      • Leung T.N.
      • et al.
      Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome.
      ,
      • Van Hook J.W.
      Acute respiratory distress syndrome in pregnancy.
      This is because fetal hemoglobin has a higher affinity for O2 than adult hemoglobin, which makes the fetus more resistant to changes in maternal O2 saturation and some degree of hypoxia.
      • Graves C.R.
      Pneumonia in pregnancy.
      ,
      • Levinson G.
      • Shnider S.M.
      • DeLorimier A.A.
      • Steffenson J.L.
      Effects of maternal hyperventilation on uterine blood flow and fetal oxygenation and acid-base status.
      Further support that a PaO2 of 60 mm Hg is adequate for fetal O2 delivery is on the basis of data from pregnant individuals living at high altitudes.
      • Sobrevilla L.A.
      • Cassinelli M.T.
      • Carcelen A.
      • Malaga J.M.
      Human fetal and maternal oxygen tension and acid-base status during delivery at high altitude.
      Although this is a chronic rather than acute exposure to hypoxia (and is accompanied by compensation such as tachypnea and relative polycythemia), most of the pregnant individuals are young and healthy and have a good reserve to tolerate even acute hypoxia.
      • Grocott M.P.
      • Martin D.S.
      • Levett D.Z.
      • et al.
      Arterial blood gases and oxygen content in climbers on Mount Everest.
      In an effort to decrease maternal morbidity and mortality, early warning models have been developed to assist in the timely recognition of acutely ill patients,
      • Singh S.
      • McGlennan A.
      • England A.
      • Simons R.
      A validation study of the CEMACH recommended modified early obstetric warning system (MEOWS).
      • Shields L.E.
      • Wiesner S.
      • Klein C.
      • Pelletreau B.
      • Hedriana H.L.
      Use of Maternal Early Warning Trigger tool reduces maternal morbidity.
      • Carle C.
      • Alexander P.
      • Columb M.
      • Johal J.
      Design and internal validation of an obstetric early warning score: secondary analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.
      with some models including SpO2 as one of the parameters.
      • Singh S.
      • McGlennan A.
      • England A.
      • Simons R.
      A validation study of the CEMACH recommended modified early obstetric warning system (MEOWS).
      ,
      • Shields L.E.
      • Wiesner S.
      • Klein C.
      • Pelletreau B.
      • Hedriana H.L.
      Use of Maternal Early Warning Trigger tool reduces maternal morbidity.
      Unlike other vital sign parameters that could directly be associated with an increased risk for maternal morbidity, the use of SpO2 at <95% was not (relative risk, 1.3; 95% confidence interval, 0.2–7.9).
      • Singh S.
      • McGlennan A.
      • England A.
      • Simons R.
      A validation study of the CEMACH recommended modified early obstetric warning system (MEOWS).
      Shields et al
      • Shields L.E.
      • Wiesner S.
      • Klein C.
      • Pelletreau B.
      • Hedriana H.L.
      Use of Maternal Early Warning Trigger tool reduces maternal morbidity.
      published a maternal early warning tool using different cutoffs for SpO2. They used an SpO2 of <90% as a single severe parameter and an SpO2 of <93% as a nonsevere parameter. However, low SpO2 (whether <90% or <93%) was a rare occurrence and was seen in <0.1% of included patients.
      • Shields L.E.
      • Wiesner S.
      • Klein C.
      • Pelletreau B.
      • Hedriana H.L.
      Use of Maternal Early Warning Trigger tool reduces maternal morbidity.
      In conclusion, the paucity of clinical data and lack of significance seen in early warning models do not provide sufficient evidence to support using an SpO2 of ≥95% as a cutoff for pregnant individuals presenting with acute respiratory distress.

      Challenges in Maintaining an O2 Saturation of ≥95%

      In nonpregnant individuals with acute respiratory failure secondary to COVID-19, current guidelines recommend starting supplemental O2 when levels drop below an SpO2 of 90% (strong recommendation, moderate-quality evidence) and suggest supplemental O2 use when SpO2 falls below 92% (weak recommendation, low-quality evidence).
      • Alhazzani W.
      • Møller M.H.
      • Arabi Y.M.
      • et al.
      Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19).
      In acutely ill patients, high-quality evidence showed that liberal O2 therapy (median baseline SpO2 of 96%) is associated with increased mortality.
      • Alhazzani W.
      • Møller M.H.
      • Arabi Y.M.
      • et al.
      Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19).
      Moreover, practice guidelines for acutely ill patients, including COVID-19 patients with acute hypoxemic respiratory failure, do not recommend administration of supplemental O2 above an SpO2 of 96% (strong recommendation, moderate-quality evidence) because it may lead to worse outcomes.
      • Alhazzani W.
      • Møller M.H.
      • Arabi Y.M.
      • et al.
      Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19).
      • Chu D.K.
      • Kim L.H.
      • Young P.J.
      • et al.
      Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.
      • Siemieniuk R.A.C.
      • Chu D.K.
      • Kim L.H.
      • et al.
      Oxygen therapy for acutely ill medical patients: a clinical practice guideline.
      In pregnant individuals, Pacheco et al
      • Pacheco L.D.
      • Saad A.F.
      • Saade G.
      Early acute respiratory support for pregnant patients with coronavirus disease 2019 (COVID-19) infection.
      also recommend that O2 therapy should be titrated to avoid SpO2 levels above 96%. Using a minimum target of 95% for SpO2 in pregnancy would make it more difficult to titrate O2 supplementation to avoid an SpO2 of >96%.
      There is a paucity of data to guide the O2 goals when COVID-19 progresses to ARDS. Generally, the goal is to maintain PaO2 at 55 to 80 mm Hg on the basis of extrapolation from the original ARDSNet trial
      • Brower R.G.
      • Matthay M.A.
      • et al.
      Acute Respiratory Distress Syndrome Network
      Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.
      and more recent use in the ACURASYS
      • Papazian L.
      • Forel J.M.
      • Gacouin A.
      • et al.
      Neuromuscular blockers in early acute respiratory distress syndrome.
      and Reevaluation of Systemic Early Neuromuscular Blockade
      • Moss M.
      • Huang D.T.
      • et al.
      National Heart, Lung, and Blood Institute PETAL Clinical Trials Network
      Early neuromuscular blockade in the acute respiratory distress syndrome.
      trials. Although there may be phenotypes of COVID-19–associated ARDS that respond to high amounts of noninvasive supplemental O2 support, such as heated high-flow nasal cannulas, many of these patients will require invasive mechanical ventilation.
      • Gattinoni L.
      • Chiumello D.
      • Caironi P.
      • et al.
      COVID-19 pneumonia: different respiratory treatments for different phenotypes?.
      ,
      • Marini J.J.
      • Gattinoni L.
      Management of COVID-19 respiratory distress.
      Indeed, some emerging data suggest that noninvasive positive-pressure ventilation (continuous positive airway pressure or bi-level positive airway pressure) may increase mortality and fail to decrease the rates of intubation in critically ill COVID-19 patients.
      • Wendel Garcia P.D.
      • Aguirre-Bermeo H.
      • Buehler P.K.
      • et al.
      Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.
      Other modern therapies for ARDS, such as prone positioning, have been used as alternative interventions to avoid invasive mechanical ventilation and improve oxygenation in COVID-19 patients,
      • Sarma A.
      • Calfee C.S.
      Prone positioning in awake, nonintubated patients with COVID-19: necessity is the mother of invention.
      ,
      • Thompson A.E.
      • Ranard B.L.
      • Wei Y.
      • Jelic S.
      Prone positioning in awake, nonintubated patients with COVID-19 hypoxemic respiratory failure.
      however, these therapies present unique challenges for pregnant individuals.
      The criteria to mechanically ventilate pregnant and nonpregnant individuals are similar. These include airway protection, hypoxia, hypercarbia, and hemodynamic instability.
      • Graves C.R.
      Pneumonia in pregnancy.
      Pregnant individuals infected with the SARS-CoV-2 delta variant are more frequently critically ill, requiring O2 support more often compared with infection with previous variants.
      • Del Rio C.
      • Malani P.N.
      • Omer S.B.
      Confronting the delta variant of SARS-CoV-2, summer 2021.
      ,
      • Wang A.M.
      • Berry M.
      • Moutos C.P.
      • et al.
      Association of the Delta (B.1.617.2) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with pregnancy outcomes.
      In pregnant individuals with acute respiratory failure secondary to COVID-19, guidelines suggest to maintain a target maternal SpO2 of ≥95% as per professional societies recommendations, whereas for nonpregnant patients, often a target PaO2 of 55 to 80 mm Hg or an SpO2 of >90% is recommend. To meet this higher goal, pregnant individuals may need increased O2 delivery by noninvasive O2 delivery methods, earlier intubation and mechanical ventilation, increasing fraction of inspired O2, mean airway pressure, or positive end-expiratory pressure. In addition, pregnant individuals will have cephalad displacement of the diaphragm, increased intraabdominal pressure, which provides mechanical evidence of a disadvantage of oxygenation, and an increased O2 consumption by the developing fetus. This increased oxygenation target is difficult to achieve, especially in patients with COVID-19 affected by the latest wave of infections attributed to the delta variant of SARS-CoV-2.
      • Del Rio C.
      • Malani P.N.
      • Omer S.B.
      Confronting the delta variant of SARS-CoV-2, summer 2021.
      ,
      World Health Organization
      Weekly epidemiological update on COVID-19.
      Thus, pregnant patients may be more likely to be exposed to increased invasive interventions when maternal oxygenation goals of 95% are unable to be maintained using noninvasive methods of O2 supplementation, with potential risks and without clear maternal or fetal benefit.
      In its guidance for managing COVID-19 patients, the SMFM suggests delivery at or after 32 weeks’ gestation in settings of refractory maternal hypoxemia.
      Society for Maternal-Fetal Medicine
      Management considerations for pregnant patients with COVID-19.
      Although an SpO2 cutoff of ≥95% seems reasonable and safe as a target, in most clinical situations, challenges in treating pregnant individuals affected by the most recent COVID-19 wave have raised questions regarding the validity of this recommendation, especially for patients at extreme preterm gestational ages. Designing a randomized controlled trial comparing the clinical outcomes for patients who were maintained at O2 saturation levels of 92% and 95 %, respectively, would be ideal and might be warranted. However, designing and completing such a trial in a timely fashion with the current COVID-19 wave is unrealistic. Individualized patient care based on maternal clinical status and gestational age is of utmost importance.

      External Fetal Monitoring as a Noninvasive Tool

      Fetal oxygenation depends on maternal oxygenation and placental perfusion. Significant disturbances in maternal oxygenation may lead to fetal hypoxia, which is often reflected as a nonreassuring fetal status during fetal heart rate monitoring.
      • Martin Jr., C.B.
      Normal fetal physiology and behavior, and adaptive responses with hypoxemia.
      External fetal monitoring can be used as an indicator of fetal well-being, and having a reassuring fetal heart rate is associated with adequate oxygenation and perfusion of the fetus.
      • Phelan J.P.
      Labor admission test.
      ,
      • Skupski D.W.
      • Rosenberg C.R.
      • Eglinton G.S.
      Intrapartum fetal stimulation tests: a meta-analysis.
      Fetal heart rate monitoring can be used as an additional vital sign that may help in the management of the maternal condition and guide the decision to move toward additional invasive interventions if needed. As long as the fetal status is reassuring, tolerating a maternal SpO2 between 92% and 96% is prudent and might prevent detrimental outcomes associated with invasive interventions that could negatively affect both mother and baby.
      Furthermore, tolerating a lower maternal SpO2 may prevent unnecessary fetal interventions that could happen at time of intubation or extracorporeal membrane oxygenation (ECMO) cannulation, which could be challenging depending on the maternal characteristics. In many instances with difficult intubations, maternal O2 saturation can transiently drop as low as 60% to 70% and is often associated with changes in variability and decelerations on thr fetal monitor.
      • Sahin F.K.
      • Koken G.
      • Cosar E.
      • et al.
      Obstructive sleep apnea in pregnancy and fetal outcome.
      Sustained nonreassuring fetal status often warrants acute interventions such as emergent cesarean delivery, which carries significant additional morbidity
      • Liu S.
      • Liston R.M.
      • Joseph K.S.
      • et al.
      Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term.
      ,
      • Ghazi A.
      • Karim F.
      • Hussain A.M.
      • Ali T.
      • Jabbar S.
      Maternal morbidity in emergency versus elective caesarean section at a tertiary care hospital.
      to the mother on top of her acute respiratory failure secondary to COVID-19. More so, in cases of very preterm pregnancies, a classical cesarean delivery may be indicated, which carries an increased risk of bleeding
      • Patterson L.S.
      • O’Connell C.M.
      • Baskett T.F.
      Maternal and perinatal morbidity associated with classic and inverted T cesarean incisions.
      ,
      • Kan A.
      Classical cesarean section.
      and long-term implications for future pregnancies.
      • Halperin M.E.
      • Moore D.C.
      • Hannah W.J.
      Classical versus low-segment transverse incision for preterm caesarean section: maternal complications and outcome of subsequent pregnancies.
      ,
      • Chauhan S.P.
      • Magann E.F.
      • Wiggs C.D.
      • Barrilleaux P.S.
      • Martin Jr., J.N.
      Pregnancy after classic cesarean delivery.

      Conclusion

      An SpO2 below 95% in a pregnant individual with COVID-19 should prompt evaluation by a healthcare provider and may require inpatient admission. For pregnant individuals on supplemental O2 for acute respiratory failure secondary to COVID-19 infection, there is a lack of convincing evidence supporting the current recommended SpO2 of ≥95%. We suggest maintaining SpO2 in a range of 92% to 96% in critically ill individuals admitted to the hospital on O2 supplementation.
      In the setting of reassuring fetal heart rate monitoring, this could possibly prevent unnecessary invasive interventions including endotracheal intubation with mechanical ventilation and ECMO. This is especially significant when the decision to escalate to these measures is based on the concern for maintaining fetal oxygenation rather than supporting the mother’s respiratory status. In these situations, external fetal monitoring can be used as an additional noninvasive tool to monitor the fetal well-being and reserve invasive interventions for maternal respiratory status indications as long as the fetus is not showing signs of distress.

      Supplementary Data

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