Editor: Jon Hyett
In the space of a few weeks SARS-CoV-2 has turned life as we know it upside down.
“Social distancing” and “flattening the curve” have become common parlance, PPE and ventilators the new currency of Governments, and “House Party” synonymous with spending Friday night (or any night of the week for that matter) on your computer with a glass of wine.
We are no doubt all feeling anxious and unsettled at the moment, but spare a thought for those that find themselves pregnant in the midst of this pandemic. Becoming a parent can be pretty stressful at the best of times, let alone right now.
Here is a two-part rundown on all aspects of COVID-19 in pregnancy to help you provide women-centred, respectful, and skilled care to pregnant patients.
Part one focuses on the science behind COVID-19 infection in pregnancy, and part two will focuses on the clinical management of pregnant COVID-19 patients.
On 31 December 2019, authorities in Wuhan, China reported an outbreak of “pneumonia of unknown aetiology”. On 7 January 2020, genetic sequencing revealed the perpetrator to be a novel coronavirus, SARS CoV-2. The disease it causes became known as COVID-19. Since then SARS CoV-2 has spread around the globe, with over two million confirmed cases and over 125,000 reported deaths.
SARS CoV-2 has been isolated from respiratory secretions, faeces, and fomites. It is thought to transmit from human to human either directly from close contact through droplet spread, where infected respiratory secretions come into contact with mucous membranes, or indirectly by touching an object contaminated by an infected person. Though airborne spread is not thought to be a major vector for transmission, the virus may be aerosolised by aerosol generating procedures (AGPs) such as intubation and the use of diathermy.
The basic reproduction number (R0) of the SARS CoV-2 is approximately 2.2, meaning for every one infection, that person will infect another 2.2 people, presuming all individuals are susceptible to the disease. Though there are limitations to interpreting this early in a pandemic, the case fatality rate (CFR) is estimated to be around 1%.
In the general population 80% of cases will be mild or asymptomatic, 15% severe enough to require oxygen therapy and 5% will require ventilation.
Pregnant women have been deemed a “vulnerable group” during the pandemic. This is in recognition of the fact that a number of the physiological, mechanical, and immunological changes that occur during pregnancy increase a woman’s susceptibility to severe infection and hypoxaemic respiratory failure, especially in the third trimester. It also reflects concerns raised by the SARS and MERS outbreaks, where pregnant women appeared to be affected more severely than the general population.
Despite well over two million reported cases of COVID-19, a literature review identified only one published case of a maternal death due to COVID-19. A further three maternal deaths in the presence of a positive SARS CoV-2 test have been reported by the media, but whether COVID-19 was the cause of death is uncertain at this time.[9–11] This compares favourably to data for SARS, which based on small data sets, had a CFR of 25% in pregnancy, compared to 10% in the non-obstetric population.
Five of the largest case series on COVID-19 in pregnancy have come from China. Between them they looked at a total of 53 pregnant women who contracted SARS CoV-2 during pregnancy and presented to hospital with infective symptoms, the majority in their third trimester.[13–17]
46 women delivered a total of 47 fetuses during the study period (one set of twins). There was one stillbirth and one neonatal death. Seven women were discharged whilst still pregnant.[13–17]
Pregnant patients appear to present with similar symptoms to non-pregnant patients, with fever and cough the most commonly reported symptoms. In the four publications which reported on maternal respiratory support, only one woman required mechanical ventilation. This suggests that in keeping with the general population, COVID-19 infection will be mild for the majority of pregnant women.[13,14,16,17]
A recent article from Colombia University in New York suggested that a high proportion of obstetric patients may be asymptomatic for COVID-19. Over the course of two weeks, all women admitted for delivery at The New York–Presbyterian Allen Hospital and Columbia University Irving Medical Centre were tested for COVID-19. Four women were symptomatic with a fever at presentation and tested positive for SARS CoV-2. Of the remaining 211 asymptomatic women, 29 (13.7%) tested positive for SARS CoV-2. Three of those developed a fever during admission, but the rest remained asymptomatic during their inpatient stay. Whether those women subsequently developed symptoms after discharge is not reported.
Within a city such as New York, which has been affected by high rates of COVID-19, the degree to which these findings mirror rates of asymptomatic infection in the non-pregnant population is unclear.
Regarding mode of delivery, it is notable that 94% of infants in the five Chinese case series were delivered via Caesarean Section (CS).[13–17] Whilst this may reflect increased rates of fetal distress, a number of units made the decision to deliver all COVID-19 positive women via CS given the lack of data regarding vertical transmission at the time.13,14 Three women had vaginal births without complication.[15,16]
There is a suggestion of an increased risk of pre-term birth in COVID-19 positive mothers. Four of the five Chinese case series reported on gestational age at delivery, observing that 16/36 (44%) of fetuses were delivered before 37 weeks (gestational age range: 31-36+3 weeks). However, the authors acknowledge that this was mainly iatrogenic in nature (either due to obstetric indications such as pre-eclampsia, or concern about potential maternal deterioration from COVID-19) rather than a manifestation of preterm labour.[13–15,17]
It is hypothesised that maternal hypoxaemia caused by COVID-19 may increase the risk of fetal distress. Three of the five case series reported on fetal status, documenting 13 cases of fetal distress and one stillbirth out of a total of 29 fetuses. The degree of fetal distress was not recorded, however, it is reassuring that all 28 live-born neonates had an Apgar score of 7 or more at one minute.[13,15,17]
For those women that recover from COVID-19 and remain pregnant, there is a theoretical increased risk of intrauterine growth restriction. Protracted maternal respiratory compromise and hypoxia is associated with Endothelin-1 and Hypoxia Inducible Factor (HIF) release, leading to placental damage from hypoperfusion. During the SARS outbreak, examination of placentas from infected mothers showed increased subchorionic and intervillous fibrin deposition, which may be associated with abnormal maternal blood flow, and reflect placental damage.
There is currently minimal information on the effects of COVID-19 infection on placental function. Further research looking at the placental histopathology of affected women is necessary to improve our understanding of how SARS CoV-2 infection can impact the placenta.
EVIDENCE REVIEW: Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study.
Many mothers are rightly concerned about the risk of vertical transmission. It is logical to assume that this can occur, but the proportion of fetuses affected and to what degree is unknown.
There is no data on the effect of SARS CoV-2 infection in the first trimester. The largest data set in pregnancy from the 2003 SARS outbreak identified seven women who were infected with SARS CoV-1 in the first trimester. Of those patients, 4/7 miscarried, 2/7 proceeded to a termination of pregnancy for social indications and 1/7 went on to deliver a healthy baby at term.
This represents a miscarriage rate of at least 57% which is significantly higher than what you would expect in the general obstetric population, where approximately 20% of pregnancies end in miscarriage. However, there was insufficient data to suggest a causal relationship. Close follow-up of women affected by COVID-19 in the first trimester will be essential to ascertain perinatal outcomes and whether there are any teratogenic effects of infection.
Most data on vertical transmission in COVID-19 has come from women infected in the third trimester. In a case series from Chen et al. they tested amniotic fluid, cord blood, neonatal throat swabs and breast milk for the presence of SARS CoV-2 in 6 of the 9 infected mothers in the study. The virus was not detected in any of these samples, suggesting no intrauterine infection occurred in these cases.
In contrast, a case series from Yu et al. found that one of the neonates tested positive for SARS CoV-2 NAAT on a throat swab at 36 hours of age. The infant was isolated from the mother at birth and placental and cord blood testing for SARS CoV-2 were negative, so whether this represents true intrauterine transmission is unclear. The neonate had mild respiratory symptoms and was subsequently discharged in good condition.
Further suggestion of vertical transmission comes from a case report by Dong et al. which reported detection of IgM to SARS CoV-2 in a neonate born at 34 weeks’ gestation to a COVID-19 positive mother. Given IgM does not cross the placenta, its detection is assumed to be a neonatal response to an in-utero infection.
Despite these reports, parents should be reassured that the vast majority of paediatric cases appear to manifest as mild disease.[21,22]
As “lock-down” measures start to take effect and “flatten the curve”, clinicians and researchers on the front line will have a chance to assess the data available to them on the outcomes of SARS CoV-2 in pregnancy and develop important follow-up studies to assess for any long-term effects.
Most journals are offering free access to research material on COVID-19 to assist professionals who are working to address the pandemic. RANZCOG has a section on its website dedicated to the latest research on COVID-19 in pregnancy and is a good place to keep abreast of new information.
An Australian national registry, “Coronavirus Health Outcomes in Pregnancy and Newborns” (CHOPAN) has been set up to study the effects of SARS-CoV-2 infection in pregnancy, and will no doubt guide our future management of patients in an Australian setting.
Though we know very little about the SARS CoV-2 infection in pregnancy, the data appears optimistic for pregnant patients. Women do not appear at increased risk of infection, case fatality rates in pregnancy appear much lower than in SARS and MERS outbreaks, and neonatal outcomes are reassuring. It is, however, inevitable that as global cases rise, more pregnant women will be affected. It is critical that robust data must be shared amongst the global community to inform scientists and clinicians on the effects of COVID-19 in pregnancy and a comprehensive strategy developed to manage these patients.
To read about the management of COVID-19 in pregnancy, jump to part 2 of this series: COVID-19 in Pregnancy Part 2.