Research Update: Pregnancy and COVID-19 Vaccination

Below is the transcript of the video and audio research update I recorded on 10th Sept 2021 on the topic of pregnancy and vaccination against COVID-19. This information is information only, and does not take the place of individualised advice and consultation with your medical team. I hope you find this useful, and please feel free to share this resource with anyone you think might be interested.

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Hello my name is Anna Cusack, I am an author, a doula, Certified Motherhood Studies Practitioner, and parent mentor. I have uni post-graduate qualifications in Clinical Exercise Physiology specialising in rehabilitation and I also spent many years working as a health professional in community and hospital settings. This is the second research update I have recorded (the first was on breastfeeding and vaccination against COVID-19), but in this video I will be discussing the academic, scientific research published to date in relation to pregnancy and vaccination against COVID-19.

Obviously there are limitations here – I am one person not a team of professional researchers, and I can only give you information from studies that have been published in English. The reading I have done is comprehensive but I am not trying to position myself as an expert in this area. I am relaying the findings of the people who are actually the experts in words that you can hopefully understand.

The date of this recording is the 10th of September 2021, all sources I mention are referenced in the video or audio notes. As time passes, new information will come to light as more studies are released, so I would encourage you to stay up to date with that. Using the Google Scholar search engine is the easiest way for the majority of people to access the abstracts or summaries of research papers, and in many cases the full text of the articles are freely available as well.

As at the time of this research review being recorded, there is much confusion and hesitation regarding vaccination amongst those who are pregnant, both within Australia and abroad. This is absolutely fair enough, no one wants to put themselves or their baby at unnecessary risk, and the advice we’ve been receiving over the last six months or so has been confusing to say the least.

The first thing to know here is that pregnant people were not included in research trials, which is standard across medical research. So early advice was based on theoretical modeling of how the vaccines operate in other adult humans, and also how they worked in studies of animals who were pregnant.

There is more and more human-specific research data becoming available now. The aim of this video is to present that data from formal research studies to you in an understandable way, so you can feel more confident discussing possible vaccination with you healthcare provider. It does not replace that conversation with your pregnancy health team in any way and the choice is ultimately up to you.

As I mentioned in the previous video on breastfeeding and vaccination, the Royal Australian College of Obstetricians and Gynaecologists (also known as RANZCOG) released a statement on the 18th August 2021 with advice for people who were trying to become pregnant, currently pregnant and/or breastfeeding. In this statement they note that

“Pregnant women are a priority group for COVID-19 vaccination, and should be routinely offered Pfizer mRNA vaccine (Cominarty) or Spikevax (Moderna) at any stage of pregnancy.

 

Pregnant women with COVID-19 have a higher risk of severe illness compared to non-pregnant women with COVID-19 of the same age. This includes an increased risk of:
-    hospitalisation
-    admission to an intensive care unit
-     invasive ventilation. 

COVID-19 during pregnancy also increases the risk of complications for the baby including a higher risk of stillbirth and of being born prematurely.”

 

So let’s unpack that statement a bit. Firstly I want to note that the RANZCOG recommendation is only talking about Pfizer and Moderna vaccines. These are the vaccines that have data for pregnancy in human subjects. Stebbings and colleagues have done studies of AstraZeneca on mice that haven’t recorded any concerns in pregnant females or their offspring, but mice are not humans. So all the research they are using and the research we’re discussing today is on Pfizer and Moderna and human mothers, pregnant people and their babies.

In the rest of this video we’re going to review the data on the other points RANZCOG raise in that statement:

  1. That pregnant people have higher risks of severe illness with coronavirus infection and the COVID-19 disease it causes, and greater need for hospital and intensive care.
  2. COVID-19 increases risk of complications for the baby, including higher birth and being born prematurely
  3. The recommendation that pregnant women and people should be offered vaccination at any stage of pregnancy, so research into the safety and effectiveness of vaccination at different points during pregnancy.

So this discussion will be in relation to both the mum or birth parent, what we know about vaccination and the developing baby in utero, and also in relation to any potential benefit of vaccination during pregnancy that may carry over into protection for the new baby direct post-birth.

Ok so, what happens with coronavirus exposure, the COVID-19 disease it causes and people who are pregnant? There are actually a lot of research studies published on this now. Rather than giving you a summary of every single one, I’m going to speak on information from a meta-analysis from the Canadian Medical Association Journal released on the 19th April, 2021. A meta-analysis is where researchers compile the data from lots of other smaller research studies so they can get a better picture of what’s going on.

So researchers Wei, Bilodeau-Bertrand, Liu and Auger read through 357 published research articles, and identified 42 studies that met their inclusion criteria. The meta-analysis was able to review data of 438, 548 pregnant people. Of that huge number of people, 7,569 had COVID-19 and 416,775 didn’t. Here’s what they found when they ran the data.

Compared with the non-COVID people studied, Infection with the SARS-CoV-2 virus during pregnancy was associated with higher rates of preeclampsia, preterm birth, stillbirth, ICU admission for the mother or parent, lower birth weight for the baby, and NICU admission after birth. Infection during pregnancy was no associated with gestational diabetes, c-section delivery, postpartum haemorrhage or neonatal death (that is death in the first 28 days after birth).

 

They then went on to prize out what happened to those mothers or parents and their babies if they had an asymptomatic or mild case of COVID compared to a severe case of the disease. They considered severe cases as people who had dyspnea (shortness of breath), were hyperventilating with a breath rate of 30 or more breaths per minute, had oxygen saturation levels that were lower than 93% (so that means their body wasn’t getting enough oxygen to the cells) if they were just breathing normal room air, or if they had symptoms of pneumonia (so fluid on the lungs).

 

Compared with mild COVID-19, severe COVID-19 was strongly associated with preeclampsia, preterm birth, gestational diabetes, ICU admission, mechanical ventilation (as in, being on a ventilator), and cesarean delivery, as well as low birth weight and NICU admission for the baby.

 

The authors conclude that “Our findings suggest that COVID-19 in pregnancy is associated with preeclampsia and preterm birth, and that severe COVID-19 can lead to considerable maternal and neonatal morbidity.” Morbidity means rates of illness, essentially.

 

This study didn’t report on demographics or population charateristics, so I’ll just mention one study by Marion Knight and colleagues called “Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS_Co-2 infection in the UK: national population based cohort study” that does.

This one was, as it says, from the UK following 427 women who were COVID-positive and admitted to hospital for their COVID-19 symptoms between 1st March 2020 and 14th April 2020. Now this study wasn’t looking at Delta, which seems to be more easily spread and may also have higher rates of hospitalization amongst the general population, but you can get a bit of an idea of what the effects of COVID and pregnancy might combine to be.

The researchers report that of the pregnant women who were admitted to hospital 56% were Black or from “other ethnic minority groups”, 69% were obese, 41% were aged 35 or over, and 34% had pre-existing comorbidities, and the ones they mentioned were hypertension (high blood pressure), gestational diabetes and asthma. Of those 427 women, 10% of them had needed respiratory support (so machines to breathe for them) and 1% (5 pregnant people) had died. Three of those deaths were attributed directly to COVID-19. Another seven patients were still in critical care when the study period was completed, and it’s not stated what happened to them. 161 women were still pregnant at the end of the study period.

Most women were in their late second or third trimester when they were admitted to hospital, so this seems to be a peak time for concern. Five of the babies also died, three for reasons unrelated to COVID-19 and in 2 cases it was unclear whether COVID had contributed to the deaths or not. Those are not pleasant statistics to read, but that is the data from the Knight and colleagues’ study.

Before we move on from this study I just want to address the higher rates of Black and “other ethnic” hospitalization in this study, and note that being white isn’t necessarily some magic protection from COVID or from disease in general. It’s more that people who are not white have so many more barriers to living well throughout their lives due to systemic racism in every system of the colonized world, as well as barriers to proper care when they have acute disease that they are more likely to have higher rates of maternal, parental and infant illness and death from just about every cause than white patients. It’s a big issue. It’s also worth not being complacent if you do get COVID-19 while pregnant and see worsening symptoms, regardless of your background.

Alright so now we have that idea of COVID-19 itself and pregnancy, let’s move on to vaccination, specifically in pregnancy. And again, we’ll be talking about mRNA vaccines, so Pfizer and Moderna specifically, not Astrazeneca/Vaxzevria.

We already spoke about what RANZCOG has to say about vaccination and the World Health Organisation says similar. Their statement from June on the Pfizer vaccine states that “WHO recommends the use of BNT162b2 in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks.” So it’s up to you to decide with your doctors and midwives where the benefit/risk line is for you.

So what can the research tell us so far? There is an article published on 1st July 2021 called “Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine” by Bookstein Peretz and colleagues. It looks at 390 pregnant women of varying gestation weeks who were vaccinated with 2 doses of Pfizer and compares that against 260 age matched non-pregnant women who got vaccinated with Pfizer.

They found that rates of rash, fever, and severe fatigue were similar in both groups, and muscule pain, joint pain, injection site pain or swelling and headache were actually less common amongst the pregnant people than non-pregnant ones. There were no significant differences in rates of those side effects according to trimester of vaccination.

They note that uterine contractions after vaccination were more likely if someone was getting their second dose in the third trimester (so 6.4% of third trimester people getting their second dose reported that compared to 1.3% for their first dose). Same goes for vaginal bleeding (1.5% of third trimester people getting their second dose reported that compared to 0.3% for their first dose), and pre-labour rupture of membranes (0.8% of third trimester people getting their second dose reported that compared to 0% for their first dose). There were a small number of reports of paraesthesia, so tingling or numbness, usually in the hands and feet as well.

Obviously on that rupture of membranes one, the women were in their third trimester and were further along than when they got their first dose, so I don’t know how much you can take from that statistic. So when this study was written up, 57 of the 390 pregnant women who were vaccinated had had their babies, with median age of birth at 39w 5d, no cases of pre-term birth, no cases of fetal or neonatal death. 2 babies went to the NICU.

In terms of whether the vaccination worked to make an immune response against coronavirus, Brookstein Peretz and colleagues found that all the pregnant and non-pregnant women who were vaccinated had virus-specific immunoglobulins in their blood, but the level was lower in pregnant than non-pregnant women.

While we’re on blood levels, I want to mention another article by Zdanowski and Wasniewski from June 2021, that looked specifically at the blood from the umbilical cord amongst healthcare workers in Poland who’d been vaccinated during their pregnancy. So the researchers looked at the blood from 16 umbilical cords on the day the babies were born, all the mothers had two doses of Pfizer. They had the first dose between the 29th and 36th week of gestation, and the second between the 32nd and 40th week of gestation, with an average of 3 weeks between doses. There were no severe pregnancy or neonatal complications noted. All of the umbilical cord blood samples had coronavirus-specific antibodies, and the cord blood actually had slightly higher concentrations of those antibodies than the blood samples they took directly from the mums.

Interestingly in the Polish study they found that the longer time it had been since the mums had their vaccinations, and the ones who had the vaccinations earlier in their third trimester had greater concentrations of antibodies in the cord blood (and assuming therefore in the baby too) than those who’d been vaccinated closer to the baby’s birth.

We know that giving pregnant women and people the whooping cough vaccine helps protect their babies after birth by giving antibodies through the placenta and cord blood, and it’s possible the same would be happening here.

There was another study by Gray and colleagues that looked at another 10 umbilical cord blood samples where mothers had been vaccinated also found that cord blood had coronavirus antibodies in it, actually at higher concentrations than what they found when the mothers had actually had coronavirus infection itself.

So these are small studies, but a potential protective effect from those antibodies may be another reason or thing you can speak with your birth care provider in relation to delayed cord clamping (waiting until the cord has finished pulsing before clipping it) if you do decide to get vaccinated. That way the baby would get as much of that cord blood and the antibodies as possible, well as all the other goodness in it into their little body while they’re too young to be vaccinated against COVID themselves.

Ok, back to safety considerations during pregnancy. There is an article called “Preliminary Findings of the mRNA Covid-19 Vaccine Safety in Pregnant Persons” which was published on April 21, 2021 by Shimabukuro and colleagues. This study looks at 3958 participants in the US who were vaccinated between 14th December 2020 and 28th Feb 2021. They were eligible to participate if they were vaccinated at any time during their pregnancy or in the periconception period, which they define as from 30 days before the last menstrual period to the time of conception. 98.8% of these were aged 25-44, 94.0% were healthcare workers and 79% were white women.

Here is the breakdown of when the women received their first vaccination dose:

2.3% during the periconception period (i.e. the six weeks before conceiving), 28.6% in the first trimester, 43.4% in the second trimester and 25.7% in the third trimester.

The study was published 2 months after the cut-off end date for vaccinations, so they can only report on 827 completed pregnancies, the rest were ongoing and we have to wait until time passes until all women birth their babies. The breakdown is that in the time between being vaccinated and the study reporting period ending 712 women birthed live babies (including 12 multiple births), and 700 of these had had their first dose in the third trimester. Rates of preterm birth, low weight for age babies, and congenital abnormalities were all within the general population ranges they provide. Unfortunately they just give whole population ranges to compare to not a population of unvaccinated women matched for age, race or ethnicity etc. to compare to.

So the authors reported no neonatal deaths (no deaths in the first 28 days of life) but there was 1 stillbirth (1 loss beyond 20 weeks gestation).

So that accounts for 713 pregnancies, leaving 114 other completed pregnancies for us to discuss. 10 of these were induced abortions for either medical reasons like ectopic pregnancy or personal ones, and 104 women miscarried, 96 of whom were under 13 weeks gestation, so within the first trimester, when that loss occurred. This sounds alarming on its own, but the authors note that they can’t provide an analysis of exact miscarriage rate until they follow up at what should be 20 weeks gestation of all of the women who were vaccinated in their periconception period and first trimester. They estimate the risk of miscarriage is around 10% for women who were vaccinated in the first trimester, which is within the ranges that are expected for first trimester losses in general populations as well, but they are waiting on data from hundreds and hundreds of women who are still pregnant before they can give exact comparative data. They don’t say it directly but we also aren’t going to have information on rates of any congenital abnormalities or risk of other health complications for the babies of women who are vaccinated in those early days (when so much development is happening quickly) until after those babies are born, so we’ve got a while to wait for that info too.

In theory, vaccination using mRNA vaccines like Pfizer and Moderna pose little risk of crossing over the placenta and into the baby, but it can’t be absolutely excluded until human babies are born to large numbers mothers who have been vaccinated at all different stages of pregnancy. If you would like to know how the vaccines work and break down in the body, I have included a link to an article in the references or notes for this research update. It’s from the HealthLine website and it gives a quick step-by-step run down on how the mRNA and also the AstraZeneca vaccines operate in the body.

In terms of when to get vaccinated, the RANZCOG statement I mentioned earlier says the best time is “as soon as you are offered one. Pfizer or Moderna vaccines can be given at any stage of pregnancy. Two doses of Pfizer or Moderna vaccine provides good protection against COVID-19, including against the Delta strain. It is recommended to have 2 doses of the vaccine, 3-6 weeks apart.”

I note that WHO’s statement on Pfizer titled “Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under Emergency Use Listing” was last updated on 15th June 2021, and it states that “WHO recommends the use of BNT162b2 [so Pfizer] in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks. To help pregnant women make this assessment, they should be provided with information about the risks of COVID-19 in pregnancy, the likely benefits of vaccination, and the current limitations of safety data.”

Herein lies the personal risk/benefit situation again, and where you feel you sit. In a recent interview on the “Feed Play Love” podcast, Professor of Midwifery from Western Sydney University Hannah Dahlen noted that as there is so much going on in terms of physical development of the baby in the first trimester and notes as I have here that much more data has been released on outcomes for babies after vaccination during the late second trimester and also third trimester. She noted that with the existing gap in the data in mind, some mothers may feel more comfortable waiting until the second trimester to be vaccinated for the wellbeing of the baby. The flipside of that is that being vaccinated earlier may give you more protection during the third trimester when you’re likely to get sicker if you become infected with coronavirus which could also impact the baby. We also don’t know yet what the ideal timing is for vaccination to allow for greater transfer of antibodies to the baby through the placenta.

It really is personal choice based on your personal risk profile and I encourage you to talk these through with your midwife, obstetrician or GP. Obviously if you’re 39 weeks pregnant and not seeing anyone and everyone else in your household is also staying home, the benefits and risks to you personally going to get vaccinated right now are very different to someone who is 10 weeks pregnant in Western Sydney who is a nurse, their partner is an ambulance officer, their older child is going to daycare and their mum who lives with you works at the supermarket, so ultimately only you can weigh it up according to your own situation and make that choice.

RANZCOG also say in their statement that if you’ve had one dose of the vaccination prior to pregnancy you can have another during pregnancy as soon as enough time has elapsed from the first vaccination, you don’t need to delay it. Some pregnant people who may have had their first dose during the week they had their last period before getting pregnant, just as an example, may feel nervous about getting their second dose during the first trimester. It’s worth noting that you do get greater protection from serious illness and hospitalisation from COVID-19 as an adult if you’ve had both vaccine doses instead of one, but if you’re able to lay really low (like you and anyone who lives with you working from home, pretty much not seeing anyone or going to risky environments during that early period) you may be able to, in consultation with your health care team, have your second dose around that 12 to 13-weeks mark instead.

There is some evidence from the UK released by Parry and colleagues in recent months that shows much higher levels of antibodies against COVID-19 with a 12-week gap between Pfizer doses rather than a shorter one. Admittedly that study is in elderly people, and it’s not undergone peer review yet by other experts in the field before being officially published, so don’t take that as gospel. My understanding is that in Australia at the moment with Delta circulating we’re being encouraged to get them closer together to get as much protection as possible rapidly. That said, your medical team would probably rather you have a second dose sometime rather than not at all, so if you feel you can keep your exposure risk very low in that early period, and you’re nervous about getting your second dose during those early weeks of pregnancy, you could at least have the conversation with your providers to determine some kind of direction and dosage gap that feels safest for you and your baby.

Ok, that’s all the information I have for you at this stage. If you have questions or want to request clarification on something please contact me on my social media, I’m @annacusackpostpartum on Instagram and Facebook, or send me an email using the contact form on my website www.annacusack.com.au.


I hope this research update has given you some information to consider and was useful to you. The references to all the articles are in the video or episode description and the same as in for the breastfeeding-related research update I did, you are welcome to go and read those articles and many other sources for yourself.


Thanks for listening or watching, remember to follow along to get the next updates and send on to anyone who you feel may be interested for personal or professional reasons in hearing this information.


 

 

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Articles cited:

Brookstein Peretz, S., Regev, N., Novick, L., Nachsol, N., Goffer, E., Ben-David, A. et. al. (2021). Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA Covid-19 vaccine. Ultrasound in Obstetrics & Gynecology, 58(3), 450-456. https://doi.org/10.1002/uog.23729

Gray, K. J., Bordt, E. A., Atyeo, C. A., Deriso, E., Akinwunmi, B., Young, N. et. al. (2021). Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. American Journal of Obstetrics and Gynecology, 225(3), 303.e1-303.e17. https://doi.org/10.1016/j.ajog.2021.03.023

Knight M, Bunch K, Vousden N, Morris E, Simpson N, Gale C et al. (2020). Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study BMJ 369 :m2107 doi:10.1136/bmj.m2107

Parry, H., Bruton, R., Stephens, C., Brown, K., Amirthalingam, G., Hallis, B., et. al. (2021). Extended interval BNT162b2 vaccination enhances peak antibody generation in older people. Advanced online publication. Doi:10.1101/2021.05.15.21257017

Shimabukuro, T. T., Kim, S. Y., Myers, T. R., Moro, P. L., Oduvebo, T., Panagiotakopoulos, L. et. al. (2021). Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. New England Journal of Medicine, 384, 2273-2282. DOI: 10.1056/NEJMoa2104983

Stebbings, R., Maguire, S., Armour, G., Jones, C., Goodman, J., Maguire, A. K. et al. (2021). Developmental and reproductive safety of AZD1222 (ChAdOx1 nCoV-19) in mice. Reproductive Toxicology, 104, pp.134-142; https://doi.org/10.1016/j.reprotox.2021.07.010

Wei, S. Q., Bilodeau-Bertrand, M., Liu, S. & Auger, N. (2021). The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. CMAJ, 193(16), E540-E548; DOI: https://doi.org/10.1503/cmaj.202604

Zdanowski, W., & Wasniewski, T. (2021). Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results. Vaccines 9(6), 675; https://doi.org/10.3390/vaccines9060675


I also referred to:

-HealthLine. AstraZeneca vs. Pfizer. Published 22nd August, 2021. https://www.healthline.com/health/astrazeneca-vs-pfizer-vaccine

-RANZCOG statement, updated 18th August: https://ranzcog.edu.au/statements-guidelines/covid-19-statement/covid-19-vaccination-information

-WHO statement on Pfizer, last updated 15th June 2021: “Interim recommendations for use of the Pfizer–BioNTech COVID-19 vaccine, BNT162b2, under Emergency Use Listing”. https://apps.who.int/iris/bitstream/handle/10665/341786/WHO-2019-nCoV-vaccines-SAGE-recommendation-BNT162b2-2021.2-eng.pdf?sequence=1