COVID-19 Updates for Pregnancy
/Since our update in March, we now have much more data – so much in fact that it may be really hard for everyone to synthesize it all. Our hope is to help a little with the synthesis and present the information out there in a digestible way – obviously we won’t be totally comprehensive, but we’ll do our best!
Pregnancy and COVID-19 Risk
The CDC released a new morbidity and mortality weekly report (MMWR) in November 2020:
Looked at data from 1/22-10/3/2020 with delay for data updates up to 10/28/2020 in both pregnant and nonpregnant symptomatic women between the ages of 15-44 (reproductive age).
409,462 symptomatic women
23,434 (5.76%) symptomatic pregnant women
Suggestion: pregnant women are MORE likely to have severe COVID-19 associated illness. After adjusting for age, race, other med conditions, pregnancy women were:
More likely to be admitted to the ICU (10.5 vs 3.9/1000 cases, ARR 3.0)
More likely to receive ventilation (2.9 vs 1.1/1000, ARR 2.9)
Receive ECMO (0.7 vs 0.3/1000, ARR 2.4)
And die… (1.5 vs 1.2/1000, ARR 1.7)
Some other interesting findings:
Older pregnant women were more likely to have ICU admission/severe disease, comparing women 35-44 with women 15-24 (19.4 vs 7.6/1000 cases)
Black women had higher risk of death (made up of 14.1% of all women involved, but represented 36.6% of deaths overall, including 26.5% of pregnancy deaths)
Increased risk of ICU admission for Asian women (ARR 6.6) and native Hawaiian/Pacific Island women (ARR 3.7)
In pregnant Hispanic women, pregnancy was associated with 2.4x risk of death
Some limitations:
COVID-19 cases rely on voluntary report by health care providers and public health officials/agencies
Reporting bias – we might report more if there is more severe disease (less likely to report asymptomatic or mild disease)
Severe outcomes might require more time to ascertain (why they had time lag of 10/28 when looking at cases reported through 10/3/2020).
Smaller studies have been performed to assess other pregnancy outcomes. Studies may be too small to be powered for these differences, but are still being actively studied:
Preterm labor/stillbirth
Overall during the pandemic:
Danish report showed decreased preterm birth rates overall;
Another UK study showed increased rates of both;,
JAMA Dec 7, 2020 in Philadelphia did not show increased rate during the pandemic. But conflictingly, a study in the same city in October showed that there was a decreased PTB rate at one hospital
Could hypothesize these varying outcomes may be due to different time periods, different lock-down methods, etc.
PEC/cesarean deliveries/PTB in people with COVID
One study from Texas looked at 3374 women who were tested for COVID, of whom 252 were positive.
In positive women, there was no difference in composite outcome of PEC w/ SF, cesarean delivery, or PTB.
Looking at PTB from the Birth and Neonatal Outcome MMRC from CDC: there was a preterm birth rate of 12.9% in women with COVID-19 infection, which was higher than general population in 2019 (10.2%), so maybe there is an increased risk for preterm delivery.
Birth and Neonatal Outcomes after COVID-19
There has been concern about perinatal infection in women who are COVID-19 positive and laboring. Fortunately we’ve got some reassuring data on this front from the CDC:
5252 women with lab-confirmed COVID-19’s babies 610 (21.3%) of infants had reported COVID results
Perinatal infection – uncommon (16, 2.6%) and occurred primarily among infants whose mother had COVID ID’ed within 1 week of delivery.
8 of the infants were born preterm (26-35 weeks) and admitted to NICU
8 term infants who were positive, one was admitted to NICU for fever and O2, the others were not admitted, and one did not have info.
COVID-19 Vaccination in Pregnant and Breastfeeding People
When we recorded the episode, we spoke primarily about the Pfizer vaccine. This information should apply in broad strokes the the Moderna vaccine as well, now that it has received approval as the 2nd mRNA vaccine.
mRNA vaccine – What is it, how does it work?
mRNA: messenger RNA. It is single-stranded RNA molecule that is complementary to one of the DNA strands of a gene. Reaching back to med school: mRNA leaves the cell nucleus and moves to the cytoplasm where they code for different protein synthesis. Ribosome will move along the mRNA, read the base sequence, and use the genetic code to translate three-base triplet (codon) into its corresponding amino acid
tRNA: which is attached to an amino acid, will match with mRNA to generate a sequence of amino acids to make up a protein
The COVID-19 mRNA vaccine gives instructions to our cells to create a “spike protein,” which is a harmless piece of protein that is found on the surface of the virus that causes COVID-19
Once the mRNA is used, the cell gets rid of the material… so you can’t get infected with COVID-19. It also doesn’t get encoded into our DNA!
Once your cell makes the protein, it presents it on the surface of the cell. The immune system will recognize that this protein doesn’t belong there and begin to build up an immune response and make antibodies, kind of like what would happen in the natural infection against COVID-19.
At the end of the process, your immune system will recognize these surface proteins from COVID-19 and have the ability to fight them off, so if you come into contact with COVID-19, your immune system will be ready
How was it developed so fast?
Most of the time, vaccine trials take a long time because there are hang-ups in things that have nothing to do with science: funding, IRBs approval, etc.
But because this was coronavirus, there was a lot of funding and momentum from Operation Warp Speed.
OWS is a partnership with the Department of Health and Human Services, CDC, NIH, Biomedical Advanced Research and Developmental Authority (BARDA), and Department of Defense
Since March, the HHS has given a TON of money to vaccine research: https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html#:~:text=August%2011%3A%20HHS%20announced%20up,the%20option%20to%20acquire%20more.
Pfizer received $1.95 billion in July for production of 100 million doses of vaccine, and Congress directed almost $10 billion to the overall effort of vaccine development/distribution. Most of the time, vaccine research does not get this much money all at once!
Is it safe?
For the Pfizer vaccine, the Phase 3 clinical trial began on July 27 and enrolled 43,661 participants, and 41,135 received a second dose
The trial concluded 11/13/2020, so there is at least 3.5 months’ worth of data. We don’t really expect long term outcomes to be different… since mRNA gets destroyed by the body so quickly.
Findings:
Looking at 28 days after first dose of vaccine (remember, we need time for the vaccine to work), there were 170 confirmed cases of COVID-19: 162 in the placebo group vs. 8 in the vaccine group.
Efficacy was consistent across age, gender, race, and ethnicity demographics.
Efficacy was 95% overall, and 94% in adults >65 years of age.
Safety in general: well tolerated across all populations, no serious safety concerns observed. The only Grade 3 adverse event >2% in frequency was fatigue (3.8%) and headache (2.0%). Older adults tended to report fewer and milder solicited adverse effects following vaccination
What about reports of the 6 people that died in the Pfizer Phase III trial?
6 people did die in the trial. 4 were in the placebo arm, and 2 were in the actual vaccine arm.
Of the two that died: 1 was reported to have serious adverse event related to arteriosclerosis and died 3 days after dose 1; the other had a cardiac arrest 60 days after dose 2 and died 3 days later. Both were > 55 years of age.
Of the 4 that died in placebo arm: 1 died 8 days after dose 1 with unknown event, one died of hemorrhagic stroke 15 days after dose 2, one died 34 days after dose 2 (unknown event), one died of MI 16 days after dose 1.
Other serious adverse events
The non-fatal SAE was 0.6% in the vaccine group and 0.% in the placebo group
Vaccine group had higher rates of appendicitis (0.04%), acute MI (0.02%), and CVA (0.02%)
Placebo arm had higher rates of pneumonia (0.03%), afib (0.02%), and syncope (0.02%)
Editorializing here: but the overall small numbers, the variety of things that occurred, and the lack of biologic plausibility in these SAEs suggest these likely happened by chance.
Should pregnant and breastfeeding people get vaccinated?
Unfortunately, pregnant and breastfeeding people were excluded from the study
Currently, the FDA has not excluded pregnant and breastfeeding people from getting the vaccine
SMFM is in agreement – recommend that pregnant and lactating people have access to the vaccine
Can engage in discussion about potential benefits and unknown risks with their providers