ROP 2020 April 3rd Breaking News: Updates on COVID in Pregnancy

ROP Breaking News: COVID in Pregnancy - April 3, 2020 Updates

Penny Wilson, MD and Heidi James, MD

Where did we leave off?

• As of  March 19th we had 4 case series out of China looking at around 35 pregnancies.
• No evidence of vertical transmission (Lancet paper which tested amniotic fluid, cord blood and breastmilk of 6 patients all negative)
• Presentation and outcomes of COVID-19 infection in pregnancy similar to non-pregnant women.

What new information do we have?

• Multiple additional case reports / case series out of China.
• A case series of 7 patients out of New York which is still in pre-publication (https://www.sciencedirect.com/science/article/pii/S2589933320300410).
• Total cases of COVID-19 in pregnancy in the published literature now at around 112 women / 113 babies (1 set of twins).
• Challenges with the literature:
• Some cases appear to be duplicated across publications
• Some are case series of babies, some are mothers
• Papers are being released in pre-proof stage
• Some have the complete paper published in English where as some have only the abstracts translated
• See Professor Jim Thornton’s blog: https://ripe-tomato.org/2020/03/22/covid-19-in-pregnancy/
• Dr. Thorton is a professor of obstetrics and gynecology in Nottingham, and is collating and summarizing these primary evidence papers on his blog as they are released.

• There’s also a systematic review in pre-proof stage of the AJOG MFM “pink journal” pooling the data from 79 cases of coronavirus epidemics in pregnancy (including SARS, MERS, COVID19 – of which 41 were COVID) (https://www.sciencedirect.com/science/article/pii/S2589933320300379
• Their conclusions – in coronavirus patients with pneumonia, pre-term birth is the most common adverse event, with higher rates of miscarriage, pre-eclampsia caesarean and perinatal death than in non-infected population.
• It’s worth bearing in mind that SARS and MERS had much higher case fatalities than we’ve seen so far in COVID, so their quoted perinatal death rate is likely an overestimate. And as we are rapidly expanding our numbers of COVID cases in the literature, the pooled coronavirus data is becoming less useful.
• In recent days we have seen news reports of maternal and fetal deaths involving COVID, but until we can see the details from case reports in the medical literature it would be unwise to make any further comment about these.

Focusing on the COVID cases that we now have in the primary literature, are the outcomes different to what we previously thought?

•  At our last review we had discussed the 1 reported neonatal death in a preterm infant with sepsis and DIC, and the stillbirth of the mother who was severely unwell on ECMO.
• We now have 3 times as many patients reported in the literature and no additional neonatal deaths, and still have zero maternal deaths.
• We can still say that most mothers have mild disease and most babies are having good outcomes.
• However, there are important new findings.
•  A case series published in JAMA (https://jamanetwork.com/journals/jamapediatrics/fullarticle/2763787) of 33 babies of COVID positive mothers at the Wuhan Childrens’ Hospital.
• 3 babies were COVID positive with positive throat swabs at days 2 and 4 but negative by day 6 or 7.
• All three babies had pneumonia and required NICU admission.
• One of the babies was more severely unwell with low apgars, respiratory distress syndrome and sepsis but his condition was thought to be mostly due to obstetric complications and prematurity (31+2) rather than directly due to COVID infection.
• “Strict infection control and prevention procedures” were implemented at delivery so the authors postulate that the source of the infection was likely to be maternal-fetal, and therefore conclude that “maternal-fetal transmission can’t be ruled out”
•  A case report (https://jamanetwork.com/journals/jama/fullarticle/2763853) and a case series (https://jamanetwork.com/journals/jama/fullarticle/2763854) – both also published in JAMA of total of 7 babies of COVID positive mothers who had serology testing after delivery.
• 6 babies were positive for SARS-CoV-2 IgG (we know IgG can cross the placenta)
• 3 babies were positive for IgM which is not thought to cross the placenta, raising the suspicion that these babies had been exposed to the virus in utero.
• However – ALL of the babies had negative PCRs on blood and throat / NP swabs, which is hard to reconcile. None of the other body fluids were tested for the virus.

There has been discussion all over twitter about vertical transmission…

• But there are still a lot of unknowns. For example, we don’t know if there was significant placental pathology that could explain these findings.
• Furthermore, a subsequent JAMA editorial (https://jamanetwork.com/journals/jama/fullarticle/2763851) has urged caution in over-interpreting these results. IgM is not usually used for diagnosis of congenital infections because it is less reliable a method compared to PCR. The pattern of degradation was also not typical of congenital infection (ie, the IgM levels dropped much faster than would be expected). So, while it’s still possible that COVID-19 is transmissible in utero, it’s also possible that this is just artefact rather than true vertical transmission.
• “More definitive evidence is needed”

What have we learned from the New York cases?

• 7 cases of COVID positive cases in pregnancy or perinatal period.
• 5 patients presented with symptoms, were swabbed and came back positive.
• 2 admitted to hospital for a couple of days for supportive care including hydration and then discharged
• 3 managed at home
• 2 patients asymptomatic, were admitted to hospital for labor induction due to obstetric reasons
• 1 had complicated labor, then caesarean with conversion to GA for obstetric reasons, and her COVID was only discovered after difficulty with ventilation and bronchospasm
• 8 hours in ICU before extubation and discharge on day 4.
• The second patient developed fever and respiratory symptoms 25 hours after delivery and then had a positive COVID swab.
• ICU admission due to severe hypertension requiring nicardine drip, complicated by kidney injury and as of day 5 was having ongoing supplemental oxygen.
• Things that stand out to me:
• Both the mothers who had more severe COVID disease had co-morbidities that we know increase the risk of COVID in the general population (elevated BMI and type 2 DM, one had chronic hypertension and one had asthma)  à so we need to particularly alert to those COVID risk factors in our pregnant patients
• Both were asymptomatic, but probably infected at the time of their admission to hospital, and both had been in contact with 15-20 staff members before diagnosis, none of whom were wearing COVID appropriate PPE.

There’s a lot of chat online and in medical circles about PPE. Where are we at with that?

• https://www.sciencedirect.com/science/article/pii/S2589933320300410
• The CDC PPE guidelines remain unchanged:
• Droplet precautions for COVID positive or PUI (Persons under investigation).
• N95 for potential aerosolization including intubation and therefore including caesarean sections due to the risk of conversion to GA.
• However, the New York paper encourages a more aggressive approach – surgical masks for every patient and every health care worker for every encounter, plus N95 masks for all COVID positive or COVID unknown cases. Whether or not this is practical given the incredible demands for PPE across the system, I’m not sure, but this is an area where there are a lot of strong opinions and advice may change with time.

Is anyone else weighing in on this debate?

• There are a couple of “expert reviews” in pre-proof also in the AJOG MFM “Pink Journal” also pushing for enhanced PPE including N95s for all contact with COVID positive patients. (https://www.sciencedirect.com/science/article/pii/S2589933320300409). They’re also advocating for surgical masks for every patient and every health care worker for every interaction, symptomatic or not.
• However, the CDC and other international colleges have not changed their PPE advice – still advising droplet precautions for COVID positive patients and n95 for aerosolization procedures eg intubation.
• There is still disagreement as to whether inhaled nitrous oxide is an AGP, and whether second stage of labor is an AGP. The US groups tending to say yes, and international groups tending to say no. We don’t have really any good data on this so it’s all based on assumption anyway.

Did anything else come out of those expert reviews?

• The paper titled Labor and Delivery Guidance for COVID-19 is a very detailed document looking at processes for screening, labor and postpartum management. Some recommendations
• Diligent screening and testing of patients due to come into the maternity unit.
• Pregnant women advised to isolate at home for 2 weeks before delivery or around 37 week to reduce risk of infection around the time of delivery
• Stuff about the design of physical space and work-flows within the maternity units to minimise cross-contamination.
• Encouraging units to engage in simulations of COVID positive patients to work out what works and what doesn’t, including donning and doffing of PPE.
• Be a bit more cautious with steroids for fetal lung maturation particularly in more severe maternal disease or later gestations where the benefit:risk ratio is less.
• While there is still a question mark over the risk of NSAIDs in COVID, consider using nifedipine instead of indomethacin for tocolysis for preterm labor.
• Avoid use of intrapartum 02 for fetal resuscitation – it doesn’t work anyway and it increases risk of exposure to maternal oral / nasal secretions.
• Conserve blood products by maximising maternal Hb prenatally and actively manage 3rd stage with oxytocics.
• Consider use of LARCs in the immediate postpartum period to reduce need for face-to-face visit down the track (eg post-placental IUD, or subdermal etonogestrel or IM depo prior to hospital discharge)
• Aim for short hospital stays with telehealth follow-up

What about pregnant health care workers?

• So, most official advice is that because pregnant women aren’t at higher risk of severe COVID, pregnant health care workers can continue to work in clinical areas with appropriate PPE.
• But, given the increased risk of preterm delivery, the risk of disruption of early mother-baby bonding and the emerging evidence of possible vertical transmission, AND the fact that these workers will soon become patients in the L&D units I think it’s wise to be cautious.
• We are in a position to advocate for our pregnant HCW patients and colleagues and I think this is a place for individual risk assessment and transition away from highest risk clinical areas if possible.

Summary

• Some indication that vertical transmission may be possible, but more evidence is needed
• We’re still seeing good outcomes for most mums and babies, but being mindful of the increased risk of severe disease in pregnant patients with comorbidities, and still needing to monitor newborns closely for signs of pneumonia and complications of prematurity.  
• Lots of differing recommendations over appropriate PPE but very little evidence – follow local guidance.
• It’s important for health services to consider the ways of reducing face-to-face visits, screening and swabbing patients appropriately and designing their physical spaces to reduce cross contamination. 

Keep doing that great obstetric care, and stay safe out there!