Covid-19 Maternal Mortality in Abu Dhabi and the Northern Emirates and a
review of all described maternal mortalities
Authors: Ghalia Ashoor-Almahri (Subspecialist in Maternal and Fetal
Medicine)1,2, Juan Acuna (Chair of the Department of
Epidemiology and Public Health)3, Saleema Wani
(Consultant in Obstetrics and Gynaecology)1, Tarek
Ansari (Consultant in Anaesthesia)1, Sally El Deeb
(Consultant in Obstetrics and Gynaecology)4, Jane
Kelly (Head of Quality)1, Paul Bosio(Consultant in
Obstetrics and Gynaecology)1
1 Corniche Hospital, SEHA Health services, Abu Dhabi, UAE
2 Harris Birthright Research Centre, Kings College Hospital, London, UK
3 Khalifa University, Abu Dhabi, UAE
4 Sheikh Khalifa General Hospital, Umm-Al-Quwain, UAE
Running title: A review of Covid-19 related Maternal Mortality
Corresponding author: Dr Ghalia Ashoor, Harris Birthright Research
Centre, Kings College Hospital, London, SE5 9RS, email:
ghalia@doctors.org.uk
Abstract
The case fatality rate of Covid-19 in pregnancies published so far
varies significantly. In our cohort of 515 women we had 3 maternal
deaths due to three varying pathologies related to Covid-19. Our first
case died due severe ARDS and a superimposed Pneumothorax, our second
case the main cause of death was Septic shock and our third case
developed Covid-19 encephalitis that resulted in brain death. There is
currently only 10 maternal mortality cases described in detail in the
literature. All our 3 cases were of South Asian origin, 2 of which had a
BMI above 35.
Introduction
The case fatality rate of Covid-19 in pregnancy varies based on the
current published studies (UKOSS 2020, Lumbreras-Marquez et al 2020).
The UK Obstetric Surveillance System (UKOSS 2020) is the largest cohort
published to date of 427 pregnant women with a positive SARS-CoV 2
RT-PCR test. In that cohort, 40 women (9%) required level 3 critical
care, of those 31 needed delivery due to COVID-19 and 9 were still
pregnant whilst four required extracorporeal membrane oxygenation. In
this study, 5 women died (3 of which were postnatal women) giving a case
fatality rate of 1.2% and a SARS-CoV 2 associated maternal mortality
rate of 5.6: 100,000 maternities (UKOSS). Whilst The percentage of women
needing critical care is slightly higher than what has been reported
from China (Phua et al 2020), the mortality rate is lower, perhaps
reflecting a lower threshold for admitting pregnant women to level 3
critical care. It is important to note that 30 women (10 antenatal and
20 postnatal) were still inpatients at the time of analyses (UKOSS).
Further, whether the maternal deaths recorded were related to Covid-19
is also unclear in this interim report.
The first Covid-19 case maternal mortality reported in the UK (see Table
1: case 1), was of a 29 year old woman of Pakistani origin with multiple
comorbidities including obesity, type 2 diabetes mellitus (T2DM), renal
tubular acidosis, asthma, and vitamin D deficiency (Ahmed et al 2020).
She also had a still born baby in her first pregnancy which may also
reflect her poor background health status. Booking investigations
revealed HbA1c of 9.7% and a high albumin creatinine ratio, correlating
with subsequent poor diabetes control on metformin and insulin and an
ultrasound scan at 26 weeks showing a large for gestational age baby and
polyhydramnios. She had over 20 hospital attendances with reduced fetal
movements and she eventually was administered corticosteroids for fetal
lung maturity. At 29 weeks’ gestation she was admitted with a fever and
had a normal chest x-ray, was treated with antibiotics and prophylactic
low molecular weight heparin (LMWH) and discharged home. She re-attended
a week later with severe breathlessness requiring 100% oxygen and
diabetes ketoacidosis. She had a caesarean section the following day
under GA. The baby was SARS-CoV 2 negative. She improved immediately
post-delivery and was extubated on day 3 of admission(?) and continued
on intermittent CPAP. However, on day 7 of admission her respiratory
function deteriorated and she complained of new onset blurred vision. A
CTPA revealed a right lower lobar pulmonary embolism with extensive
bilateral ground-glass and patchy solid consolidation consistent with
Covid-19 pneumonia and a head CT revealed basilar artery thrombosis.
Both her respiratory and neurological conditions rapidly deteriorated
and care was withdrawn the following day. This case highlights the
thrombotic complications of Covid-19 in pregnancy (Ahmed et al 2020).
In another large cohort of 308 pregnant women with Covid-19 disease
reported from Mexico as of the 17th of May, there were
7 maternal deaths (Lumbreras-Marquez et al 2020). This study reports a
case fatality rate of 2.3% in pregnant women with Covid-19 disease. The
demographics and clinical characteristics of those that survived was
compared to those that died and this illustrated that those that
suffered a maternal mortality were older, were more likely to be
diabetic and obese and have other comorbidities. However, of the 7
maternal deaths only two received intensive care and only one was
intubated, raising questions about the quality of maternal care provided
to these women. The complications of Covid-19 in pregnancy and the exact
causes of the maternal deaths were not described.
In another report from New York on 43 infected pregnant women who
presented to hospital for obstetric and non-obstetric reasons, only 2
women needed ICU admission and both recovered (Breslin et al 2020). This
cohort included women that were screened for the disease (33% were
asymptomatic) and therefore likely reflects less severe disease at
presentation. A much larger case series of 462 pregnant women from New
York confirmed to be Covid-19 positive by RT-PCR between the
1st of March to the 6th of May was
recently published (Blitz et al 2020). The number of women that were
classified as severe or critical was 70 (15%) and 13 (2.8%) women were
admitted to intensive care due to acute hypoxia. Among this group, 2
died (see Table 1: Case 2 and 3) and 11 were discharged from hospital.
Therefore, the case fatality rate in this cohort was 0.4%, still much
lower than the UK and Mexican data (Blitz et al 2020, Lumbreras-Marquez
et al 2020, UKOSS 2020).
The maternal mortality due to Covid-19 in Iran was recently published
from seven level three maternity hospitals over a 30 day period. The
total number of infected pregnant women is not reported and therefore
the case fatality rate is not known in this cohort of women
(Hantoushzadeh et al 2020). They had 9 pregnant women with severe
Covid-19 disease (defined by a positive SARS-CoV 2 RT-PCR nucleic acid
testing with dyspnea, blood oxygen saturation <93% on room
air or partial pressure of arterial oxygen to fraction of inspired
oxygen <300 and an available death certificate) and there were
7 mortalities among these (See Table 1: case 2-8). All Covid-19
pneumonia was treated with osteltamivir, hydroxycholorquine,
lopinavir/ritonavir, and low molecular weight heparin prophylaxis. If
any of the following clinical signs occurred, loss of consciousness,
respiratory rate >24, blood pressure <90/60 mmHg,
multilobar lung infiltration on CT or chest x-ray or hypoxemia
<90%, then ribavirin was added to the treatment protocol.
Steroid treatment was not recommended and all these patients were
admitted before 8th of March except one case. Antibiotic administration
was dependent on the attending physician’s clinical judgement. The cause
of death in all seven cases is described in table 1 with the timeline of
deterioration and intubation. The seven women were all in the second and
third trimesters of pregnancy. Two of the women had no comorbidities,
one was obese, three were over the age of 35 years and one suffered from
gestational diabetes in pregnancy but none of them had significant
hypertension, cardiovascular disease, asthma or renal disease. The women
died between 5 to 32 days from the initiation of symptoms. As for the
two survivors reported with severe disease, one was still on a
ventilator for 35 days at the time of reporting and the other recovered
following extubation after 20 days.
We are reporting our Covid-19 related mortality cases at the largest
maternity hospital in United Arab Emirates (UAE) providing tertiary
referral services. Corniche Hospital has been instrumental in the care
of pregnant women in the Emirate of Abu Dhabi during this pandemic. As
the primary designated referral centre, minimal care was provided for
Covid-19 positive pregnant women outside our facility elsewhere in the
Emirate of Abu Dhabi (Abu Dhabi city, Western region and Al Ain). We
also provide outreach services and consultation to hospitals in the
Northern Emirates of UAE. The Covid-19 related mortalities in pregnancy
occurred in May and June; two of these occurred in the Emirate of Abu
Dhabi and one was a referral case from the Northern Emirates. These
cases should include all the Covid-19 related mortalities in the UAE
outside the emirate of Dubai.
UAE Case A:
A Filipino (see Table 1: case 11) primigravida in her late twenties at
27 weeks’ gestation was referred to our Hospital from a private facility
with a 1 week history of fever and a dry cough. She was otherwise fit
and well with no relevant past medical history or recognized
co-morbidities and a body mass index of 22. She had been tested with her
partner 3 days previously and the RT-PCR results were negative. On
arrival she had a borderline temperature of 37.7 degrees after taking
paracetamol at home. Her oxygen saturations were 97% in room air and
her cardiovascular parameters were all stable. She was admitted to an
isolation room but 3 hours later her oxygen saturations dropped to 92%
in room air, with a respiratory rate (RR) of 25/min, blood pressure (BP)
91/56 mmHg and a heart rate (HR) of 95 beats per minute. She was
initially started on 5l/min oxygen through a nasal cannula and commenced
on piperacillin-tazobactam antibiotics, anti-viral
(lopinavir-ritonavir), hydroxychhloroquine and prophylactic low
molecular weight heparin (LMWH). Three hours later, her BP dropped to
82/47mmHg with a stable pulse rate of 99 beats per minute and oxygen
saturations at 99% on the 5 L/min nasal oxygen and RR of 20
breaths/min. She was given a fluid challenge and started on a higher
treatment dose of LMWH twice a day. The chest x-ray illustrated mid and
lower zone pulmonary consolidation and ground glass patchy opacification
consistent with COVID-19 pneumonia. A few hours later her saturations
continued to drop on oxygen to 90% and therefore she was started on 15
L/min oxygen using a non-rebreathing mask whilst her BP remained stable
at 99/59mmHg. She was moved to HDU for continuous monitoring where she
initially remained stable until she attempted to mobilise when she
desaturated again to 84%. Arterial blood gas (ABG) showed partial
pressure of oxygen (PaO2) of 66, prompting her team to switch her to 20
L/min high flow nasal cannula (HFNC). Her BP was recording borderline
low and therefore she was given another fluid challenge which stabilised
her readings. The oxygen delivery was increased to 30 L/min HFNC and a
repeat ABG showed a PaO2 of 67.5 and evidence of hyperventilation.
Proning was discussed with her but she was unable to tolerate it as she
was getting exhausted with increasing shortness of breath. She was
therefore started on non-invasive ventilation (NIV) using BIPAP with a
PEEP of 8 which improved her gasses significantly to a PaO2 of 172.
Since her ABG were normal, the Fio2 was gradually decreased from 0.95 to
0.7 over the subsequent 24 hours. Although her oxygen saturations were
normal, repeat ABG showed a PaO2 of 83 and therefore the
FiO2 (fraction of inspired oxygen) was again increased
accordingly. She was stable and repeat arterial blood gasses (ABG) were
normal until the morning of day 8 of admission (and day 7 of critical
care) with a PaO2 of 65 on BiPAP (bilevel positive airway pressure) and
FiO2 of 0.7%. Throughout the day the
FiO2 was gradually but repeatedly increased to increase
her saturations but her PaO2 was still 66 and she was getting
increasingly physically exhausted. She was therefore intubated that same
evening and a central line inserted under ultrasound guidance. The
patient remained unstable with little improvement in her PaO2 and was
showing signs of haemodynamic instability when the decision to proceed
with an emergency Caesarean section was made. This was performed bedside
in the ICU and was surgically uneventful. Her oxygen saturation
continued to drop and a bedside chest ultrasound showed a loss of the
sliding sign and therefore a pneumothorax was suspected. Repeat chest
x-ray confirmed a massive right-sided tension pneumothorax with right
lung compression and mediastinal shift to the left in addition to severe
progressive bilateral pulmonary consolidation. A chest drain was
successfully inserted, and the central line was changed to a quad lumen
catheter, but she continued to deteriorate despite full ventilation and
inotropic support and arrested 2 times before resuscitation was stopped
after 5 cycles of unsuccessful CPR (cardiopulmonary resuscitation) on
the occasion of her third cardiac arrest in the early hours of the next
morning.
UAE Case B:
A Nepalese woman (see Table 1: case 12) in her mid-thirties was admitted
from the Emergency Department(ED) with severe ARDS on presentation. She
was cyanotic on admission, with saturations of 30% and was very
agitated. She was clearly pregnant and was booked for antenatal care at
a private facility but no documentation on gestational age was available
on presentation. Collateral history suggested she was approximately 26
weeks into her first pregnancy and had been symptomatic at home for 5
days prior to arriving in hospital. Although she had an elevated BMI of
36, she had no other reported co-morbidities. She was immediately
intubated in the ED and started on antibiotics and prophylactic LMWH and
transferred to the ICU. In the ICU she was also commenced on antivirals
as well as hydroxycholorquine and needed norepinephrine to maintain a
MAP above >65. A chest x-ray demonstrated extensive patchy
airspace opacity bilaterally in keeping with Covid-19 pneumonia. A
bedside ultrasound indicated a likely gestational age of 26 weeks and a
decision was made for delivery following multidisciplinary discussions
in order to improve maternal resuscitation measures; intramuscular
betamethasone was given for fetal lung maturity. On Day 2 following
admission, an uncomplicated caesarean section was done bedside in ICU
and a 800g baby boy was delivered in reasonable condition, intubated and
transferred to NICU. During the Caesarean section, intra-operative
oxygen saturations dropped to 78% and there was a mild drop in blood
pressure for which she received 500mls of albumin. She was started on
hydrocortisone and meropenem postoperatively and proning administered
for 16 hours per day. Repeat nasopharyngeal RT-PCR taken after the
antivirals were started was negative for Covid-19 but the patient
continued to demonstrate clinical and radiological signs consistent with
active progressive Covid-19 infection. On Day 3 post-Caesarean Section
the dose of LMWH was increased to a therapeutic dose and the following
day a repeat chest x-ray showed a mild improvement of the previously
noted bilateral pulmonary ground glass opacification with no evidence of
pleural effusion or pneumothorax. On Day 5 she was clinically stable,
afebrile and inflammatory markers had all improved; all the culture
results were negative and therefore the 7 day course of antibiotics and
steroids were stopped. However the next day she suddenly deteriorated
rapidly over the space of one hour with a temperature of 40 degrees,
tachycardia and a gradual but sustained drop in blood pressure that was
unresponsive to norepinephrine. She developed deep ST depression in
association with worsening hypotension which was then followed by a
ventricular escape rhythm with progressive bradycardia and then
asystole. The cause of death was likely overwhelming septic shock.
UAE Case C
A Filipino lady in her late thirties (see Table 1: case 13) who
presented at 22 weeks and has been symptomatic for 5 days with a fever,
cough, runny nose sore throat and shortness of breath. She is para 3 and
had three previous caesarean sections and her risk factors are a BMI of
39 and not receiving any antenatal care during this index pregnancy. On
admission her RR was 28/min, oxygen saturation was 93%, BP 130/85 and a
HR of 105 beats/min and an oxygen mask with 2 L/min was needed to
maintain her oxygen saturations at 97%. She was swabbed for COVID-19
the day prior to admission and the result was positive on admission. Her
chest x-ray demonstrated patchy opacification involving both lung
fields. She was started on antibiotics and LMWH on the same day. She
deteriorated a few hours later and required increase in oxygen flow to 7
L/min to maintain the saturations of 95% and her respiratory rate was
stable at 28. The next day she developed metabolic acidosis likely
secondary to diabetes with a serum bicarbonate of 11 and ketonuria, her
previous history of gestational diabetes puts her at high risk of
pre-existing undiagnosed diabetes mellitus for which she was treated. In
addition, she also required increasing oxygen demand, and was started on
HFNC and was treated with another broad spectrum antibiotic, an IL-6
inhibitor, low dose methylprednisolone and the dose of LMWH was
increased to therapeutic dose. The same day further hypoxia resulted in
the patient being intubated and mechanically ventilated. A bedside scan
showed a singleton pregnancy with an EFW corresponding to 24 weeks of
gestation and normal amniotic fluid volume. She remained stable on FiO2
of 40% but continued to spike fevers so Tazobactam-piperacillin was
changed to Merpenum. Her respiratory condition continued to improve and
sedation was tapered down on day 10 of admission, however she was
unresponsive and sluggish pupillary reflexes were noted. An MRI brain
was performed which showed diffuse brain oedema with inferior brain
herniation likely secondary to COVID-19 related encephalitis. Therefore
dehydration measures were started and a CT brain a few days later was
suggestive of global hypoxic injury with impending conisation. A
neurological review demonstrated absent pupillary response, absent
corneal reflex, no response to deep painful stimuli, spontaneous
triggered responsiveness likely due to sparing of lower brain stem. A
multidisciplinary team concluded that maternal outcome is poor due to
irreversible neurological insult, and since the mothers cardiovascular
condition is stable delivery will be delayed until a fetal ultrasound
reassessment is performed at 28 weeks gestation and steroids for fetal
lung maturity administrated. However in the case of maternal
cardiorespiratory deterioration then delivery would be expedited. She
started to spike temperatures again nearly 3 weeks after admission and
blood, urine and sputum cultures all grew Candida Auris and she was
started on antifungal treatment. A repeat fetal ultrasound scan showed a
normally growing fetus with an EFW of 1.15kg and since the temperature
spikes continued with increasing frequency and severity a decision was
made to expedite delivery to avoid fetal compromise and she had an upper
segment caesarean section and cord gasses were normal. The placental
histology was examined and there was no evidence of an inflammatory
process and a swab from the placenta showed no growth on culture. A
repeat CT brain 5 weeks after admission showed more progressive ischemic
changes of the cerebellar hemispheres. Using the brain death policy
issued by the UAE government, brain death determined by neurological
criteria is equivalent to the death of the individual even though the
heart continues to beat and spinal cord function may persist.
Discussion
The total number of pregnant women with COVID-19 disease identified in
Abu Dhabi so far is 515 (unpublished data) and therefore our case
fatality rate in Abu Dhabi is 0.5% lower than what has previously been
published (UKOSS 2020, Lumbreras-Marquez et al 2020). All 10 mortalities
described due to COVID-19 disease that have been published so far have
occurred during the 2nd or 3rdtrimester of pregnancy and our three cases also occurred in the second
half of pregnancy (see Table 1). This is consistent with the 2009 H1N1
influenza pandemic (Siston et al 2010), where only 7% of the maternal
deaths occurred in the first trimester and 27% occurred in the second
and the vast majority (64%) occurred in the third trimester. The most
common comorbidity in these women is the raised BMI (5 of the 13 women
had a BMI > 35), being of South Asian origin (4 of
the 13 cases), advanced maternal age in 3 women and T2DM in 2 women.
The cause of death in our case series varied significantly indicating
the wide range of COVID-19 related pathology, the first case was due to
ARDS and a superimposed pneumothorax, the second case was overwhelming
sepsis and the third case was secondary to encephalitis. The maternal
death occurred between 5 to 32 days from symptom onset and between 2 to
22 days from admission date (see Table 1). Overall, cause of death was
secondary to ARDS in 10 of 13 cases (77%) and a pneumothorax
complicated this in 3 of the 13 cases (23%) which is therefore a likely
adverse outcome of the lung disease due to COVID-19 and patients should
be closely monitored for such complications. One patient suffered from
both a pulmonary embolus as well as an ischemic stroke and was on LMWH
from day 1 of symptoms however this patient has multiple comorbidities
(see Table 1: case 1) which also highlights the thrombotic complications
of COVID-19 disease in addition to the background increased risk of
pregnancy and emphasises the need to start high treatment dose as soon
as patient is admitted. Of course in cases where the delivery of the
baby may be indicated then unfractionated heparin can be used for easier
drug reversal. It is important to note that the 3rdcase is still on respiratory support and patient remains hospitalised at
the time of this publication. Sepsis and septic shock contributed to the
cause of death in 3 cases and in our second case (see Table 1: case 12)
was the main cause as she deteriorated very quickly after the cessation
of antibiotics after 9 days of administration even though clinically she
was stable with improving inflammatory markers.
The rate of deterioration was rapid in all three cases in UAE from the
point of admission to NIV or intubation indicating that patients were
likely to have delayed hospital attendance until symptoms worsened which
may also indicate that overall adverse outcome of other non-COVID-19
related pregnancy complications is likely to have increased during this
pandemic and this needs further investigations. The majority have
started antibiotics and antivirals as well as a LMWH on date of
admission. However the treatment protocol differs in different units due
to evolving knowledge and experience of the disease and there is a need
for a more standardised evidence based approach as more evidence becomes
available. The data published from the RECOVERY trial on the significant
reduction in mortality in patients that need oxygen therapy is
encouraging and should be taken into account when treating COVID-19
pregnant patients however data on pregnancy specific outcomes is still
awaiting (Horby et al. 2020).
Disclosure of Interest: Nil
Contribution of authorship: GAA was in charge of the concept
and did the initial writing of the manuscript. The manuscript was edited
by PB, JA, TA, SW. JK and SD was in charge of data collection.
Ethical approval: Ethical approval was granted for this study
by the Abu Dhabi Covid-19 Research IRB Committee. Consent was obtained
from the next of Kin of the 3 cases of Maternal mortality for the
publication of this manuscript.
Funding: No funding was received or requested.