Outcome predictors and patient progress following delivery in pregnant and postpartum patients with severe COVID-19 pneumonitis in intensive care units in Israel (OB-COVICU): a nationwide cohort study

Abstract

Background: A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery.

Methods: In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery).

Findings: From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO₂), SpO₂ to fraction of inspired oxygen (FiO₂) ratio (S/F ratio), partial pressure of arterial oxygen to FiO₂ ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores.

Interpretation: In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation.

Funding: None.

Figure 1

Changes over time in the daily census of number of ICU admissions, use of mechanical ventilation, use of ECMO, and death among pregnant and postpartum patients during the study period Feb 1, 2020, to Jan 31, 2022 ICU admission data for pregnant patients occurred predominantly in waves, corresponding to the national pandemic waves for the general population (marked with predominant viral strains). National census data were obtained from the Israel Ministry of Health COVID-19 dataset. ECMO=extracorporeal membrane oxygenation. ICU=intensive care unit. IPPV=invasive positive pressure ventilation.

Figure 2

Predictors of adverse maternal outcome For statistical analysis, adverse maternal outcome was assessed as a composite of IPPV–ECMO–death. (A–F) All measures of oxygenation at admission (SpO₂, S/F ratio, P/F ratio, and ROX index) and the SOFA and PORCH scores were highly predictive for the IPPV–ECMO–death composite (p<0·0001). (G–I) Unlike other published studies of COVID-19, age and comorbidities (APACHE-II) were not predictive for the IPPV–ECMO–death composite, which likely reflects the fact that all patients in the OB-COVICU study were pregnant females of childbearing age with few comorbidities. APACHE-II=Acute Physiology and Chronic Health Evaluation II. ECMO=extracorporeal membrane oxygenation. IPPV=invasive positive pressure ventilation. P/F ratio=ratio of partial pressure of arterial oxygen to fraction of inspired oxygen. PORCH=PEEP, oxygenation, respiratory support, chest x-ray, haemodynamic support. ROX index=ratio of oxygenation (S/F ratio) to respiratory rate. SOFA=Sequential Organ Failure Assessment. S/F ratio=ratio of SpO₂ to fraction of inspired oxygen. SpO₂=oxygen saturation by pulse oximetry.

Figure 3

Pooled data of maternal outcome by patient group Maternal outcome (worst of no IPPV, IPPV, ECMO, or death) is shown above the occurrence of pulmonary and renal complications for each group. The delivery-critical group and the postpartum group had markedly worse maternal outcomes. ECMO=extracorporeal membrane oxygenation. IPPV=invasive positive pressure ventilation. *Delivery-critical and postpartum groups versus other groups: p<0·0001.

Figure 4

Longitudinal severity scores and duration of ICU stay by patient group Pooled longitudinal SOFA scores (A), pooled longitudinal PORCH scores (B) for the entire ICU stay, and Kaplan-Meier cumulative survival analysis of ICU duration (C). There was a marked difference between groups (p<0·0001), with worse SOFA and PORCH scores on admission and slower trajectory of improvement, and longer ICU stay in both the delivery-critical and postpartum groups when compared with all other groups (p<0·0001). ICU=intensive care unit. PORCH=PEEP, oxygenation, respiratory support, chest x-ray, haemodynamic support. SOFA=Sequential Organ Failure Assessment.

Figure 5

Longitudinal SOFA (A) and PORCH (B) scores for the delivery-critical and delivery-non-critical groups Scores were recorded for 5 days before and 10 days after delivery. The day of delivery was a significant inflection-point covariate for the PORCH score (p<0·001) but not for the SOFA score (p=0·09). PORCH=PEEP, oxygenation, respiratory support, chest x-ray, haemodynamic support. SOFA=Sequential Organ Failure Assessment.