Case of the Month #23

Stuart Edwardson
Arlene Wise

A 34 year old primigravida of Asian ethnicity at a gestation of 36+4 and BMI 24 has presented to obstetric triage. She describes a persistent cough for the last 4 days which is getting worse and has been advised by her GP to attend for further investigation. She is otherwise fit and well, and has had a low-risk pregnancy with no concerning features.

On examination, she is found to have SpO2 of 88% on room air, and a respiratory rate of 30. 40% oxygen delivered through a Venturi device improves this to 94%, although she is said to be progressively ‘tiring’. Foetal scanning and CTG show no concerning features. She is afebrile, but has lymphocytes of 1.2 and CRP of 240.

A SARS-CoV-2  PCR test is positive.

ICU have been contacted to discuss the most appropriate next steps for this patient’s care.

What is the risk profile of a pregnant woman with SARS-CoV-2?

The ICNARC report of January 2021 describes 12% of critically ill women aged between 16-49 years with COVID-19 as being pregnant or recently pregnant (1). This is a significant increase since the first wave, as reported in COVID-19 ICNARC April 2020. Whether this is just due to overall increased community prevalence or a factor of the new variant is unknown at present.

While this is a population we usually think of as being physiologically robust, we know that pregnant women were at especially high risk of developing complications during the relatively recent H1N1 pandemic (2). And pregnancy does present a challenge to the critical care community in this regard. An already impaired respiratory capacity, frequent need for expediting delivery and/or operative intervention, the necessity of MDT management of both mother and baby, logistical barriers to appropriate settings of clinical care and inclusion in therapeutic trials are but a few.

Epidemiology

A systematic review and meta-analysis of 77 international cohort studies (3) showed that pregnant women are less likely to report symptoms of SARS-CoV-2compared to non-pregnant women of reproductive age. However, pregnant women were also much more likely to require ICU admission and mechanical ventilation (OR 1.62 and 1.88 respectively). As with H1N1, women with SARS-CoV-2 were at increased risk of preterm birth requiring neonatal intensive care.There is a strong iatrogenic aetiology to this.

Another review found a 7% ICU admission rate for pregnant women compared with 4.2% for their nonpregnant counterparts. 74% of infections were detected in the third trimester of pregnancy (4), although there will be significant underreporting of asymptomatic and mild cases.

Both studies found risk of severe COVID-19 was increased with maternal age above 35, increased BMI >35, chronic hypertension, and pre-existing diabetes. Of particular note, a high proportion of women with severe COVID-19 were from black and minority ethnic groups. All of these characteristics are consistent with previous maternal mortality reports, and indeed within the non-pregnant COVID-19 population.

We have to be particularly cognisant of this evidence when organising maternity services and assessing pregnant patients. These women should be advised that data shows them to be at particular risk and therefore advised to seek help early if they have any concerns at all.

What are the common clinical findings in pregnant women with SARS-CoV-2?

A study of over 23,000 pregnant women in the USA found that the most common symptoms reported were: cough (50.3%), headache (42.7%), and muscle aches (36.7%) (5).

A systematic review (3) found that common laboratory findings in the pregnant population included lymphopenia (35%), leucocytosis (27%), elevated procalcitonin (21%), abnormal liver chemistries (11%), and thrombocytopaenia (8%). Leukocytosis can be normal in pregnancy, and many of these other laboratory findings could be consistent with other disease states (eg pre-eclampsia).

77% of pregnant women with hospitalised SARS-CoV-2 display ground-glass opacification on chest radiograph.

Allotley et al (3) found that in this population: 

  • 49% had pneumonia
  • 30% received oxygen by cannula
  • 13% had severe disease
  • 4% were admitted to an intensive care unit (ICU)
  • 3% received invasive ventilation
  • 0.8% received extracorporeal membrane oxygenation (ECMO)
  • 0.6% died

Most notably, this study was performed prior to the second and third waves, where we have seen higher numbers of pregnant women hospitalised with this virus but reassuringly less mortality (1).

How can we optimise oxygenation in this population?

Maternal physiology

Pregnancy has multiple anatomical and physiological changes that have implications for the intensivist. Early hormonal effects result in a hyperdynamic circulation. A decrease in systemic vascular resistance leads to a compensatory increase in stroke volume and heart rate to maintain arterial pressure and uteroplacental oxygenation. Plasma volume increases by 40-50%, with red blood cell mass increasing by only 20%. The resulting dilutional anaemia impairs tissue oxygenation further. At 38-40 weeks there is around a 30% decrease in cardiac output on moving from a lateral to supine position. As the uteroplacental circulation possess no powers of autoregulation, any reduction in blood pressure will result in hypoperfusion and foetal acidaemia.

To impair matters further, global oxygen requirement is increased by 60% during pregnancy. An overall increase in minute volume aims to mitigate this, resulting in a respiratory alkalosis. As the uterus expands, it encroaches onto the diaphragm, reducing functional residual capacity (up to 30% when supine). Parturients therefore become hypoxaemic very quickly during episodes of apnoea.

Ventilatory strategies and prone positioning

Current critical care management of these patients is largely as it would be for any non-pregnant patient with a few added considerations.

Ideally, ventilation for pregnant patients should target a relative hypocapnia while still aiming to maintain lung-protective tidal volumes and plateau pressures. When severe lung pathology prevents this, mild hypercapnia is generally acceptable. However, hypercapnia for prolonged periods has been shown to reduce uterine blood flow and increase foetal ICP in animal models.

Achieving plateau pressures of less than 30 cm H2O may be challenging due to pressure from a gravid uterus. Oesophageal pressure monitoring is an option to help determine accurate transpulmonary pressure by distinguishing from chest wall pressure.

It is common to employ high PEEP strategies when managing ARDS. The known physiologic effects of this include decreased preload and cardiac output. This is of particular importance in a patient with a gravid uterus and significant risk of aortocaval compression. PEEP greater than 10 cm H2O should be used with caution. Left lateral tilt or manual uterine displacement should be used to mitigate the physiological consequences of aortocaval compression at all times if greater than 20 weeks gestation.

Deepened sedation and paralytics to improve oxygenation are not contraindicated in pregnancy, but may need to be given in larger doses owing to the increased volume of distribution in the obstetric patient (6).

Prone positioning in intubated patients with ARDS has proven benefits for oxygenation and mortality. However, pregnant women were excluded from the trials that produced these results. Pregnancy in the second and third trimester has long been thought of as a contraindication to proning, with only a few published case studies showing its safety (7). Tolcher et al (6) have recently published their own local guideline for proning both awake and intubated pregnant patients.

What is the profile of pregnant women who have died in the UK from SARS-CoV-2?

Maternal deaths from SARS-CoV-2 in the UK

The MBRRACE-UK report on maternal deaths normally compiles cases over a 3-year period in the UK. A rapid report on SARS-CoV-2 reviewed the deaths of 10 pregnant patients with coronavirus in the period March to May 2020 (8). 7 of the 10 women who died were from black, Asian, and minority ethnic groups.

MBRRACE describes much quicker recognition of viral symptoms and definitive diagnosis of infection compared to the 2009 H1N1 pandemic. However, it discussed a highly variable level of care provided thereafter. In particular, recognition and management of the deteriorating patient was delayed. Much of the ‘obstetric review was performed by junior staff, and after the women gave birth there was a scarcity of further obstetric and midwifery review’[8].

Service Pressures

Where these sick women were cared for has been highlighted as a particular problem by MBRRACE. They were treated in areas of the hospital unable to manage their multiple problems. MBRRACE reinforces the need for leadership, the need for regular senior review and co-ordinated multi-disciplinary and specialist input which should be continued into the extended postpartum period.

In one case, when deterioration was recognised, an emergency caesarean section was then undertaken but by a junior member of obstetric staff and then the patient returned to the same inappropriate clinical area. Respiratory function improved shortly after delivery but then subsequently deteriorated 24 hours after.

RCOG have published criteria for recognising a deteriorating pregnant patient with COVID-19 (9); signs of decompensation include:

  • FiO2>0.4 (titrated to keep SpO2>94%)
  • Respiratory rate > 30/minutes
  • Reduction in urine output
  • Drowsiness
  • (Even if oxygen saturations are normal)

Critical Care Availability

Those women that did receive critical care, all did so in temporarily repurposed settings such as operating theatres or recovery areas. They were usually cared for by staff redeployed from different roles, who were both unfamiliar with critical care equipment and looking after a pregnant or post-partum patient. Critical care services must be aware of, and adhere to, the standards of care set out in GPICS version 2 (4.10) on care of the critically ill pregnant (or recently pregnant) woman and Care of the critically ill woman in childbirth: enhanced maternal care (10, 11).

Multiple triage areas were using general adult early warning scores which failed to pick up on a deteriorating obstetric patient. Modified Early Obstetric Warning Scores (MEOWS) are available, however were likely to have been in short supply in these emergency areas (12). There is likely to have been minimal training in the use of these scores in general acute medical and emergency areas.

What drugs are approved for management of pregnant women?

Pregnant women have historically been excluded from trials of therapeutic interventions, and coronavirus is no different. However, they were included in the RECOVERY Trial and most arms have been open to recruitment.

Through RECOVERY we know that pregnant patients hospitalized with COVID-19 should receive steroids. However, Dexamethasone should not be given due to implications for fetal brain development and growth. Instead, the pregnant population should receive prednisolone 40md once a day or hydrocortisone 80mg IV twice daily for 10 days or until hospital discharge, whichever is shorter (13).

If dexamethasone is needed for fetal lung maturation then that should be given as normal, no other steroids are needed for those days.

Pregnant women were also eligible for Tocilizumab in the RECOVERY trial, and indeed 3 received it. Four nation guidance (Interim Clinical Commissioning Policy) would suggest that it is not given ‘unless clearly necessary’ in pregnancy and as part of an MDT discussion due to lack of safety evidence. However, if a pregnant women is requiring respiratory support in a critical care area for COVID-19 then this makes consideration of Tocilizumab ‘clearly necessary’. Tocilizumab, and other biologics, have been and are used in pregnancy for inflammatory conditions when other medications do not suffice, eg: RhA. Most maternity units and maternal medicine networks will have experience of this and can provide reassurance.

What about thromboprophylaxis?

We know that patients with severe COVID-19 have increased incidence of thrombotic disease. Pregnant women are already physiologically at increased risk. One death described in the MBRRACE report resulted from a sagittal sinus clot despite appropriate prophylactic  anticoagulation. The RCOG advise that all pregnant women admitted to hospital with confirmed or suspected COVID-19 should receive prophylactic LMWH unless delivery is expected within the next 12 hours. Enhanced dosing in critical care cases should be part of an MDT discussion. This should extend until at least 10 days following hospital discharge (9).

Women who are asked to self-isolate at home are encouraged to stay active and mobile. A further risk assessment should be performed by maternity services with COVID-19 being an additional risk factor and LMWH provided if indicated.

Can pregnant and breastfeeding women get vaccinated?

Numerous vaccines are being evaluated for prevention of COVID-19, but pregnant/lactating women were excluded from these initial trials. The first vaccines to become clinically available are based on mRNA or protein subunits and do not contain infectious virus (either SARS-CoV-2 or a vector virus).

The Joint Committee on Vaccination and Immunisation (JCVI) published updated advice on the 30 December 2020 and confirmed the available data do not indicate any safety concerns or harm to pregnancy, and vaccination in pregnancy should be considered where the risk of exposure to SARS-CoV-2 infection is high or cannot be avoided (health and social care workers) (14) or the woman has an underlying condition that puts her at very high risk of serious complications of COVID-19. Similar advice was issued for breastfeeding women (9). Trials of the vaccine in pregnant women are being planned in the US and UK.

What other major resources are there to provide up-to-date guidance on this topic?

Current UK Guidance

Early guidance suggested that if infection was confirmed, timing of delivery should be guided by gestation, maternal and foetal conditions and comorbidity. Induction of labour with eventual instrumental delivery to avoid maternal exhaustion was favoured. Prompt caesarean delivery is favoured if there are signs of acute organ failure or foetal distress (15). These women need to be managed by a senior multidisciplinary team, including obstetricians, critical care physicians, and obstetric anaesthetists.

The WHO currently advise that it is still unknown as to whether vertical transmission exists (16). To date, no active virus has been detected in amniotic fluid or breastmilk. Many possible cases have been reported in the setting of third-trimester maternal infection within 14 days of delivery, with likely multifactorial cause. Mothers with symptoms or diagnosed COVID-19 are advised that they can still breastfeed and maintain normal contact with their baby while maintaining good hand hygiene and wearing a surgical mask during periods of contact.

Take Home Messages

  • Pregnant and postpartum women with COVID-19 in hospital are less likely to show signs and symptoms of infection compared to non-pregnant women
  • This patient population are at an increased risk of admission to ICU
  • Increasing maternal age, high BMI, and pre-existing comorbidities are risk factors for severe disease
  • The majority of women that died with SARS-CoV-2 in the initial MBRRACE Report were of black, Asian and minority ethnic groups
  • Pregnant women were not included in the original studies relating to proning for ARDS management. There are currently some case reports showing its safety in both awake and intubated pregnant women
  • These patients require regular senior decision making and continual MDT collaboration
  • Timing and mode of delivery is entirely dependent on maternal condition and comorbidities, foetal condition and comorbidities, and gestational age.
  • Consideration of LMWH thromboprophylaxis, its dose, and its timing are of key importance
  • Note that many of the deaths in the MBRRACE report happened after an initial period of clinical improvement after delivery, followed by sudden deterioration

References

  1. ICNARC report on COVID-19 in critical care. 15 January 2021
  2. Carlson A, Thung SF, Norwitz ER. H1N1 Influenza in Pregnancy: What All Obstetric Care Providers Ought to Know. Rev Obstet Gynaecol 2009;2(3): 139-145.
  3. Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 2020;370: m3320.
  4. Khalil A, Kalafat E, Benlioglu C, O’Brien P, Morris E, Draycott T, et al. SARS-CoV-2 infection in pregnancy: A systematic review and meta- analysis of clinical features and pregnancy outcomes. E-Clinical Medicine 2020; 25: 100446.
  5. CDC. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status – United States 2020.
  6. Tolcher MC, McKinney JR, Eppes CS, Muigai D, Shamshirsaz A, Guntupalli KK, et al. Prone Positioning for Pregnant Women with Hypoxaemia Due to Coronavirus Disease 2019 (COVID-19). Obstet Gynecol 2020;136(2): 259–61.
  7. Samanta S, Samanta S, Wig J, Baronia AK. How safe is the prone position in acute respiratory distress syndrome at late pregnancy? Am J Emerg Med 2014;32(6): 687.e1–3.
  8. Knight M, Bunch K, Cairns A, Cantwell R, Cox P, Kenyon S, et al. Saving Lives, Improving Mothers’ Care Rapid Report: Learning from SARS-CoV-2-related and associated maternal deaths in the UK March – May 2020. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2020.
  9. Royal College of Obstetricians and Gynaecologists. Coronarvirus (COVID-19) Infection In Pregnancy. Published 19th Feb 2021.
  10. Faculty of Intensive Care Medicine. Guideliens for the Provision of Intensive Care Services. June 2019.
  11. Royal College of Anaesthetists. Care of the Critically Ill Woman in Childbirth. August 2018.
  12. Healthcare Safety Investigation Branch. National Learning Report Maternal death: learning from maternal death investigations during the first wave of the COVID-19 pandemic. February 2021.
  13. Saad AF, Chappell L, Saade GR, Pacheco LD. Corticosteroids in the Management of Pregnant Patients With Coronavirus Disease (COVID-19). Obstet Gynecol 2020;136(4): 823-826.
  14. Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination. 30 December 2020.
  15. Favre G, Pomar L, Qi W, Nielsen-Saines K, Musso D, Baud D. Guidelines for pregnant women with suspected SARS-CoV-2 infection. Lancet Infect Dis 2020;20(6): 652-653.
  16. World Health Organisation. Coronavirus disease (COVID-19): Pregnancy and childbirth. https://www.who.int/news-room/q-a-detail/coronavirus-disease-covid-19-pregnancy-and-childbirth. Accessed 20 Nov 2020.