show pregnant women opt for covid vaccination during pregnancy or not?

1. COVID VACCINATION DURING
PREGNANCY
DR. ANUSHIKA KEDAWAT

2. BACKGROUND
• IN THE LAST 2 DECADES, COV HAS BEEN
RESPONSIBLE FOR 2 LARGE EPIDEMICS: THE
SEVERE ACUTE RESPIRATORY SYNDROME (SARS)
WITH A CASE-FATALITY RATE OF ABOUT 10.5%
AND THE MIDDLE EAST RESPIRATORY SYNDROME
(MERS) WITH CASE FATALITY RATE OF 34.4%.
• TOWARDS THE END OF 2019, A NOVEL
MUTATION OF COV (LABELED AS SARS–
CORONAVIRUS-2) WAS IDENTIFIED AS THE
CAUSE OF A SEVERE RESPIRATORY ILLNESS,
CALLED CORONAVIRUS 2019 (COVID-19), THAT
TYPICALLY PRESENTS WITH FEVER AND COUGH.
INFECTED PEOPLE SHOW ABNORMAL FINDINGS
AT DIAGNOSTIC IMAGING, SUGGESTIVE FOR
PNEUMONIA.

3. INTRODUCTION
• THE SARS-COV-2, A NON-SEGMENTED
ENVELOPED POSITIVE-SENSE RNA VIRUS,
IS A Β-CORONAVIRUS.
• COVID‐19 IS SPREAD BY RESPIRATORY
DROPLETS AND DIRECT CONTACT
(WHEN BODILY FLUIDS TOUCH ANOTHER
PERSON'S EYES, NOSE OR MOUTH, OR
AN OPEN CUT, WOUND OR ABRASION).
THESE PARTICLES RANGE FROM LARGER
RESPIRATORY DROPLETS TO SMALLER
AEROSOLS.
• THE MOST COMMON SYMPTOMS ARE
FEVER (43.8% CASES ON ADMISSION AND
88.7% DURING HOSPITALIZATION) AND
DRY COUGH (67.8%). DIARRHEA IS
UNCOMMON (3.8%). LYMPHOCYTOPENIA
IN 83.2% OF PATIENTS ON ADMISSION.
•

4. • ON ADMISSION,
GROUND‐GLASS
OPACITY IS THE
MOST
COMMON
RADIOLOGIC
FINDING ON
COMPUTED
TOMOGRAPHY
(CT) OF THE
CHEST (56.4%).
•OTHER SYMPTOMS: SHORTNESS OF BREATH OR DIFFICULTY
BREATHING, FATIGUE, MUSCLE OR BODY ACHES, HEADACHES,
NEW LOSS OF TASTE OR SMELL, SORE THROAT, CONGESTION
OR RUNNY NOSE, NAUSEA OR VOMITING.

5. • Several testing methods have been developed to
diagnose the disease. The standard diagnostic
method is by detection of the virus’ nucleic acid by
real-time reverse transcription polymerase chain
(rRT-PCR), transcription-medicated
amplification(TMA), or by reverse transcription
loop-mediated isothermal (RT-LAMP) from
a nasopharyngeal swab.
Preventive measures include physical or
social distancing, quarantining, ventilation
of indoor spaces, covering coughs and
sneezes, hand washing, and keeping
unwashed hands away from the face. The
use of face masks or coverings has been
recommended in public settings to
minimize the risk of transmissions.
Several vaccines have been developed and
many countries have initiated mass
vaccination campaigns.

6. COVID VACCINE
• A COVID-19 vaccine is a vaccine intended to provide acquired
immunity against severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), the
virus causing coronavirus disease 2019 (COVID-19). Prior to the COVID-19
pandemic, there was an established body of knowledge about the structure and
function of coronaviruses causing diseases like severe acute respiratory
syndrome(SARS) and Middle East Respiratory Syndrome(MERS), which enabled
accelerated development of various vaccine technologies during early 2020. On 10
January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID
and by 19 March, the global pharmaceutical industry announced a major
commitment to address COVID-19.
• In Phase III trials, several COVID-19 vaccines have demonstrated efficacy as high as
95% in preventing symptomatic COVID-19 infections. As of April 2021, 14 vaccines
are authorized by at least one national regulatory authority for public use: two RNA
vaccines (Pfizer–BioNTech and Moderna), five conventional inactivated
vaccines (BBIbp-CorV, CoronaVac, Covaxin, WIBP-CorV and CoviVac), five viral vector
vaccines (Sputnik Light, Sputnik V, Oxford–AstraZeneca, Convidecia, and Johnson &

7. • Many countries have implemented
phased distribution plans that
prioritize those at highest risk of
complications, such as the
elderly, and those at high risk of
exposure and transmission, such
as healthcare workers. Single
dose interim use is under
consideration in order to extend
vaccination to as many people as
possible until vaccine availability
improves.
According to British Fertility
Society and Association of
Reproductive and Clinical
Scientists There is absolutely
no evidence, and no
theoretical reason, that any
of the vaccines can affect the
fertility of women or men.

8. TO VACCINATE OR NOT TO VACCINATE ?
• Since the pandemic began, pregnant people have faced a difficult choice: to
vaccinate or not to vaccinate.
• Pregnant women with symptomatic COVID-19 have a higher risk of intensive care
unit admissions, mechanical ventilation and death compared to non-pregnant
reproductive age women. Increases in preterm birth and still birth have also been
observed in pregnancies complicated by the viral infection.
• The risk of severe disease or even death from COVID-19 — while small — is higher
during pregnancy. More than 82,000 coronavirus infections among pregnant
individuals and 90 maternal deaths from the disease have been reported in the U.S.
as of last month.
• But when the coronavirus vaccines were first authorized in December, scientists
knew little about how well they might work in pregnant women, who had
been excluded from the clinical trials.
• There's very little data on whether the COVID-19 vaccines are safe and effective

9. • The JCVI (Joint Committee On Vaccination And Immunization) now advises that if a pregnant
woman meets the definition of being clinically extremely vulnerable, then she should
discuss the options of COVID-19 vaccination with her obstetrician and/or doctor. This is
because their underlying condition may put them at very high risk of experiencing serious
complications of COVID-19. The most likely relevant groups of pregnant women are:
Solid organ transplant recipients
Those with severe respiratory conditions including cystic fibrosis and severe asthma
Those who have homozygous sickle cell disease
Those receiving immunosuppression therapies sufficient to significantly increase risk of
infection
Those receiving dialysis or with chronic kidney disease (stage 5)
Those with significant congenital or acquired heart disease
• Additionally, pregnant women who are frontline health or social care workers, including
carers in a residential home, can also discuss the option of vaccination. This is because the
risk of exposure to COVID-19 may be higher, even if they have a lower risk of experiencing
complications if they are otherwise well.

10. • The benefits and risks of COVID-19 vaccination in pregnancy should be
discussed on an individualized basis. This should include a discussion around
the lack of safety data for these specific vaccinations for pregnant or
breastfeeding women, and an acknowledgement that there is no known risk
associated with giving other non-live vaccines to pregnant women.
The JCVI also now advises that
there is no known risk in giving
these vaccines to breastfeeding
women. Breastfeeding women
should therefore be offered
vaccination if they are
otherwise eligible, for example
if they are a frontline health or
social care worker, including a
carer in a residential home.
Women should be advised that
there is lack of safety data for
these specific vaccinations in
breastfeeding.

11. • According to ROYAL COLLEGE OF OBSTETRICIANS AND GYNAECOLOGISTS,
Women who are pregnant
• There is no known risk associated with giving non-live vaccines during
pregnancy. These vaccines cannot replicate, so they cannot cause infection
in either the woman or the unborn child.
• Although the available data do not indicate any safety concern or harm to
pregnancy, there is insufficient evidence to recommend routine use of
COVID-19 vaccines during pregnancy.
• JCVI advises that, for women who are offered vaccination with the Pfizer-
BioNTech or AstraZeneca COVID-19 vaccines, vaccination in pregnancy
should be considered where the risk of exposure to Severe Acute
Respiratory Syndrome coronavirus 2 (SARS-CoV2) infection is high and
cannot be avoided, or where the woman has underlying conditions that put
them at very high risk of serious complications of COVID-19. In these
circumstances, clinicians should discuss the risks and benefits of

12. • JCVI does not advise routine pregnancy testing before receipt of a COVID-19 vaccine.
Those who are trying to become pregnant do not need to avoid pregnancy after
vaccination.
Women who are breastfeeding
• There is no known risk associated with giving non-live vaccines whilst breastfeeding.
JCVI advises that breastfeeding women may be offered vaccination with the Pfizer-
BioNTech or AstraZeneca COVID-19 vaccines.
• The developmental and health benefits of breastfeeding should be considered along
with the woman’s clinical need for immunisation against COVID-19, and the woman
should be informed about the absence of safety data for the vaccine in breastfeeding
women.

13. • The CHM (Commission on Human Medicines) has also reviewed
further data for the Pfizer/BioNTech vaccine as it has become
available and has recommended the following changes:
•Pregnancy and women who are
breastfeeding - the vaccine should
only be considered for use in
pregnancy when the potential
benefits outweigh any potential
risks for the mother and baby.
Women should discuss the benefits
and risks of having the vaccine with
their healthcare professional and
reach a joint decision based on
individual circumstances. Women
who are breastfeeding can also be
given the vaccine. This advice is in
line with pregnancy and
breastfeeding advice for the Oxford
University/AstraZeneca vaccine.

14. • A study published recently in The American Journal of Obstetrics and
Gynecology shows the vaccines are not only safe and effective for pregnant and
breastfeeding women, they may also offer some protection for their babies.
• Though limited — with a sample size of 131 — the study is the largest to date on
the topic. The 131 participants had been vaccinated with either the Pfizer or
Moderna vaccine; 84 were pregnant, 31 were lactating, and 16 were nonpregnant
18- to 45-year-old women. The study involved patients and researchers at Brigham
and Women's Hospital, Massachusetts General Hospital and the Ragon Institute.
• Blood samples were collected at the time of the first and second dose of vaccine,
and again after six weeks.
• The levels of antibodies was similar between the groups.
• And when researchers compared the antibody levels to those of women who had
been sick with COVID-19 during pregnancy, the antibody levels in response to the
vaccine were higher.
• That finding "suggests that even if you've had COVID infection, getting the vaccine
will lead to a more robust antibody response."
#1:

15. • Side effects from the vaccinations were mild and similar to those of
nonpregnant people, including soreness at the injection site after the
first dose and some muscle aches, headache, fever and chills after
the second dose.
• But perhaps the most exciting discovery: Antibodies were also found
in umbilical cord blood and breast milk.
• The process can be likened to that of the flu vaccine: When given
during pregnancy, it produces antibodies that cross the placenta and
are "protective for the baby for the first several months of life," she
says.
• The hope is the COVID vaccine will be similar, although it's not yet
clear if it will protect the baby from getting sick or how long that
protection would last.
• Future research should focus on determining the timing of
vaccination that optimizes delivery of antibodies through the
placenta and breast milk to newborns.

16. • Collier and colleagues conducted an exploratory, descriptive study of
103 women, ages 18-45, who received an mRNA COVID-19 vaccine
(54 percent received Pfizer; 46 percent received Moderna). The
scientists found similar levels of vaccine-induced antibody function
and T cell responses in all non-pregnant, pregnant and lactating
women after their second vaccine dose. Additionally, both pregnant
and non- pregnant women who received the mRNA vaccines
developed cross-reactive immune responses against the COVID-19
variants of concern B.1.1.7 and B.1.351.
• "The COVID-19 mRNA vaccines raised robust immune responses in
pregnant, lactating, and non-pregnant non-lactating women," said
senior corresponding author Dan. H. Barouch, MD, Ph.D., Director of
the Center for Virology and Vaccine Research at BIDMC. "Additionally,
the vaccine-elicited antibody responses were greater than antibody
responses seen after COVID-19 infections. These findings add to the
emerging data that support the use of these vaccines in pregnant and
lactating women."
#2:

17. • In another study, a research team from Northwestern University and the Ann
and Robert H. Lurie Children’s Hospital of Chicago examined the placentas
from 200 women who gave birth between April 2020 and April 2021.
Eighty-four of the women had received either the Pfizer or Moderna vaccine
during pregnancy; the remainder had not received any coronavirus vaccine.
• The placentas from vaccinated women were not any more likely to show
signs of injury or abnormality than those from unvaccinated women, the
researchers found.
• “These data build upon the emerging data that’s come out about these
vaccines and their safety in pregnant people,” Dr. Miller said. “These are
translational data that suggests the placenta doesn’t see any injurious
impact of the vaccine. And that’s really fantastic.”
• The findings have limitations, she acknowledged. Because the vaccines were
only authorized recently, most of the women in the study were vaccinated in
the third trimester of pregnancy, and many of them were health care
workers, who were among the first people eligible for the shots.
#3:

18. • Pregnant patients who decline vaccination should be supported in
their decision. Regardless of their decision to receive or not receive
the vaccine, these conversations provide an opportunity to remind
patients about the importance of other prevention measures such as
hand washing, physical distancing, and wearing a mask.
• Expected side effects should be explained as part of counseling
patients, including that they are a normal part of the body’s reaction
to the vaccine and developing antibodies to protect against COVID-
19 illness.
• Women under age 50 including pregnant individuals can receive any
FDA-authorized COVID-19 vaccine available to them. However, they
should be aware of the rare risk of TTS (thrombosis with
thrombocytopenia syndrome) after receipt of the Janssen COVID-19
vaccine and that other FDA-authorized COVID-19 vaccines are
available (i.e., mRNA vaccines).

19. COVID-19 VACCINATION IN PREGNANT AND LACTATING
WOMEN
EMILY H. ADHIKARI, MD, CATHERINE Y. SPONG, MD
FEBRUARY 8, 2021
• Pregnant women with severe or critical coronavirus disease 2019 (COVID-19) infection are at
increased risk for preterm birth and pregnancy loss. In studies of hospitalized pregnant women
with COVID-19, which have included between 240 and 427 infected women, the risk for
preterm delivery (both iatrogenic and spontaneous) has ranged from 10% to 25%, with rates as
high as 60% among women with critical illness. The primary risk to a pregnancy appears to be
from maternal illness. In addition, pregnant women may be at higher risk for severe illness and
death caused by COVID-19 compared with nonpregnant women. In an analysis of national
surveillance data that included pregnancy status of 409 462 women with symptomatic COVID-
19 illness through October 3, 2020, the adjusted risk ratio in pregnant women (vs those of
similar age and not pregnant) was 3.0 for intensive care unit admission, 2.9 for mechanical
ventilation, and 1.7 for death. Thus, preventing critical COVID-19 infection is important for
both mother and fetus.
• Vaccination during pregnancy is common to prevent maternal and infant morbidity from other
infectious diseases. Vaccination is specifically recommended to prevent both influenza and
pertussis. The clinical data on safety and efficacy of influenza vaccination are abundant. In a
randomized trial of 3693 pregnant women in Nepal, influenza immunization was associated
with a relative reduction in maternal febrile influenza like illness by 19% and relative reductions
of low birth weight by 15% and infant influenza disease by 30%. These benefits were
demonstrated following maternal immunization in either early or late gestation.

20. • Likewise, following early studies that demonstrated rapid decay of maternal pertussis antibody
passively transferred to the neonate, a study that included 74 504 mother-infant pairs demonstrated
an 85% relative reduction in infant pertussis illness following maternal vaccination in the third
trimester compared with postpartum. The Tdap vaccine has been recommended for pregnant
women during each pregnancy by the Centers for Disease Control and Prevention since 2012 in an
effort to reduce the sharp increase in pertussis cases and deaths that occurred from 2011 to 2012.
• While the mRNA platforms of the available COVID-19 vaccines are distinct from both influenza and
Tdap vaccines now used during pregnancy, mRNA platforms have been in development for the last
decade. Similar mRNA vaccines have been used in clinical trials targeting other infections such as
Zika, as well as several types of cancer (such as breast cancer and melanoma). As an immunogenic
but noninfectious, nonintegrating platform, mRNA vaccines have potential benefits over live-
attenuated virus vaccines, inactivated or subunit vaccines, and DNA-based vaccines. There is no risk
of acquiring infection from the vaccine. While no specific studies have evaluated the ability of the
lipid nanoparticle vaccine to reach the fetus following vaccination, it is likely that the local muscle
cells take up the lipid nanoparticles and initiate transcription to stimulate the immune response.
• Even though pregnant and lactating women were not included in the development and clinical
evaluation of COVID-19 vaccines and treatments, the US Food and Drug Administration (FDA) and
the Advisory Committee on Immunization Practices left open the option for pregnant and lactating
women to receive the vaccine. Without data, guidance from professional societies is necessarily

21. • These organizations must balance the risk of COVID-19 infection to the pregnant and lactating
woman with the potential or theoretical risks from the vaccine to the pregnant woman and her
developing fetus or the lactating woman and her newborn.
• Thus, the guidance from professional societies and agencies has been limited, without an explicit
recommendation for COVID-19 vaccination in pregnancy. These societies, including the American
College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, have
continued to advocate for making COVID-19 vaccines available to pregnant and lactating women
even after the recent statement by the World Health Organization (WHO) on January 26, 2021,
explicitly recommending against vaccination of pregnant women using the Moderna vaccine except in
select circumstances. The WHO statement was revised on January 29, 2021, to include more
permissive language, that “pregnant women at high risk of exposure to SARS-CoV-2 (e.g. health
workers) or who have comorbidities which add to their risk of severe disease, may be vaccinated in
consultation with their health care provider.”
• It is now clear that early neonatal COVID-19 infections are rare, but whether maternal immune
response to infection protects the fetus remains unknown. Despite reports of severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) IgG detected in newborns with negative IgM and negative
results on polymerase chain reaction, SARS-CoV-2–specific antibodies appear to be inefficiently
transferred across the placenta following third-trimester maternal infection compared with antibody
transfer following infection with influenza or pertussis. Nevertheless, changes in SARS-CoV-2–

22. • Furthermore, the gestational age of de novo maternal antibody production influences the level
of SARS-CoV-2–specific antibody that is detected in cord blood specimens, implying there
may be an ideal time for maternal vaccination prior to delivery to optimize protection of the
fetus.
• The lack of data for use of mRNA vaccines during lactation is reflected in recommendations
from the Academy of Breastfeeding Medicine, which state: “During lactation, it is unlikely that
the vaccine lipid would enter the blood stream and reach breast tissue. If it does, it is even
less likely that either the intact nanoparticle or mRNA transfer into milk. In the unlikely event
that mRNA is present in milk, it would be expected to be digested by the child and would be
unlikely to have any biological effects.”
• The organization further states that potential unknown risks should be weighed against the
potential benefit of neonatal protection from infection via passive transfer of antibodies from
breast milk.
• Given the continued advocacy by obstetric societies for inclusion of pregnant and lactating
women in the initial large clinical efficacy trials, why is there such limited evidence to guide
vaccination recommendations? A major reason neither pregnant nor lactating women were
included in COVID-19 vaccine trials is the concern of liability over the potential adverse
effects on a fetus of a new product administered in pregnancy. This lack of inclusion of these
populations in new therapeutic studies is well documented. Without strategies to mitigate
litigation it is unlikely that studies of new therapeutics will willingly include these subgroups.
This results in a difficult situation for drug developers and clinicians. Although new therapies

23. • Given the importance of reducing risk of COVID-19 for pregnant and lactating women and their
neonates, it is essential to determine the safety profile of these vaccinations in real time. Capturing data
on adverse effects and safety profile is important both to provide the data for women and to provide
accurate expectations. The known adverse effects, such as fever, chills, and muscle aches, may concern
a pregnant or lactating woman and thus follow-up calls to their clinicians may be essential both for
reassurance and to reduce the burden on emergency departments. Rigorously designed studies with
proactive data collection to record both vaccine-related symptoms as well as obstetric outcomes will
advance current understanding of these events. In addition, women who were pregnant have
inadvertently participated in the ongoing trials. It would be helpful if these data were systematically
analyzed. As systematic and proactive data on COVID-19 vaccination in pregnant and lactating women
are gathered, evidence-based recommendations regarding mRNA vaccination to reduce harms from
COVID-19 will replace expert opinion.
• COVID-19 causes significant morbidity and mortality, with respiratory illness requiring hospitalization
in 5% to 6% of all SARS-CoV-2–infected pregnant women. Given what is known about the COVID-19
vaccines, the limited data regarding COVID-19 vaccines in pregnant and lactating women from those
who have been immunized, and use of other vaccines during pregnancy, physicians can empower
women to make an informed decision. With an understanding of the important practice of vaccination in
pregnancy, the use of other vaccines during pregnancy, the efficacy and safety of COVID-19 mRNA
vaccines in nonpregnant populations, and their mechanism of inducing an immune response, clinicians
can outline the benefit of prevention of COVID-19 illness, as well as the undefined but possibly limited
risk to the fetus, and potential benefit to the neonate. As part of the discussion, clinicians should

24. Preliminary Findings of mRNA Covid-19 Vaccine Safety in
Pregnant Persons
Tom T. Shimabukuro, M.D., Shin Y. Kim, M.P.H., Tanya R. Myers, Ph.D., Pedro L. Moro, M.D., Titilope
Oduyebo, M.D., Lakshmi Panagiotakopoulos, M.D., Paige L. Marquez, M.S.P.H., Christine K. Olson,
M.D., Ruiling Liu, Ph.D., Karen T. Chang, Ph.D., Sascha R. Ellington, Ph.D., Veronica K. Burkel, M.P.H., for
the CDC v-safe COVID-19 Pregnancy Registry Team*
• BACKGROUND
Many pregnant persons in the United States are
receiving messenger RNA (mRNA) coronavirus disease
2019 (Covid-19) vaccines, but data are limited on their
safety in pregnancy.
• METHODS
From December 14, 2020, to February 28, 2021, we
used data from the “v-safe after vaccination health
checker” surveillance system, the v-safe pregnancy
registry, and the Vaccine Adverse Event Reporting System
(VAERS) to characterize the initial safety of mRNA Covid-
19 vaccines in pregnant persons.

25. • RESULTS
A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-
site pain was reported more frequently among pregnant persons than among nonpregnant
women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958
participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which
115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among
participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm
birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported.
Although not directly comparable, calculated proportions of adverse pregnancy and neonatal
outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar
to incidences reported in studies involving pregnant women that were conducted before the
Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the
most frequently reported event was spontaneous abortion (46 cases).
• CONCLUSIONS
Preliminary findings did not show obvious safety signals among pregnant persons who
received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of
large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal,
pregnancy, and infant outcomes.

26. PREGNANCY, POSTPARTUM CARE, AND COVID-19 VACCINATION
IN 2021
SONJA A. RASMUSSEN, MD, MS; DENISE J. JAMIESON, MD, MPH
FEBRUARY 8, 2021
• More than a year has passed since coronavirus disease 2019 (COVID-19), caused by severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognized in China. SARS-CoV-2
has spread rapidly throughout the world and continues to cause major morbidity, mortality,
and societal disruption globally. The recent authorization by the US Food and Drug
Administration (FDA) of 2 vaccines against COVID-19 has raised hopes for an end to the
pandemic, but given the many challenges with vaccine availability, distribution, and hesitancy
as well as the emergence of variants that might result in lower vaccine efficacy or overcome
natural immunity, it is likely that SARS-CoV-2 will continue to circulate.
• Whether pregnancy increases susceptibility to COVID-19 remains unknown. Many hospitals
instituted universal SARS-CoV-2 screening for individuals presenting for labor and delivery,
providing information on the frequency of asymptomatic infection among pregnant individuals,
and seroprevalence studies of pregnant individuals confirmed that, as with the nonpregnant
population, asymptomatic infection is common. However, given the lack of data from universal
screening of an appropriate comparison group (ie, nonpregnant women of reproductive age
with similar levels of exposure), susceptibility to SARS-CoV-2 infection during pregnancy has
not been assessed. Data on SARS-CoV-2 prevalence among pregnant individuals from universal
screening identified risk factors for infection including race/ethnicity, insurance status, and
issues related to where people live (eg, those who lived in high-density neighborhoods were

27. • Although data were initially unclear as to whether pregnant individuals are at increased risk of severe
complications from COVID-19, a large study from the Centers for Disease Control and Prevention
(CDC) provided data suggesting an increased risk. Among more than 450 000 symptomatic women
of reproductive age with COVID-19 for whom pregnancy status was known, admission to an
intensive care unit, invasive ventilation, extracorporeal membrane oxygenation, and death were all
more likely among pregnant individuals than among nonpregnant women of reproductive age. Non-
Hispanic Black individuals accounted for a disproportionate number of deaths. Symptoms in
pregnant individuals (eg, cough, headache, muscle aches, and fever) were similar to those in
nonpregnant women, although most symptoms were reported less often among pregnant individuals
than nonpregnant women.
• Several studies of pregnancy outcomes suggest that preterm birth might occur more often among
infants born to individuals with COVID-19, although findings have been inconsistent. In a systematic
review, preterm birth was 3 times more common in individuals with COVID-19 than among those
uninfected, with rates of 16% vs 6%, respectively. However, whether this difference is due to direct
effects of infection or maternal illness or is iatrogenic is unknown. Some but not all studies have
suggested that stillbirths occur more often among SARS-CoV-2–infected individuals or during the
pandemic. For example, in an analysis from the UK, the rate of stillbirths was 2 to 3 times higher
among pregnant individuals during vs before the pandemic, with rates of 9.3 vs 2.4/1000 births,
respectively, although whether the increase is related to SARS-CoV-2 infection or other pandemic-
related factors is unknown.

28. • Intrauterine transmission of SARS-CoV-2 has been documented but appears to be rare. The
reasons for this are unknown, but could be related to lower expression of the ACE2 receptor and
the serine protease TMPRSS2 that are necessary for SARS-CoV-2 cell entry. Transmission via
breast milk appears to be unlikely; among 64 samples from 18 mothers, one sample tested
positive for SARS-CoV-2 RNA, but no replication-competent virus was detected.
• Data regarding mother-to-infant transmission in the postnatal period have been reassuring when
appropriate precautions are taken. In a study of 116 SARS-CoV-2–positive mothers who breastfed
their 120 newborns, all newborns tested negative for SARS-CoV-2 and were asymptomatic. In this
study, the infants roomed in with their mothers in a closed Isolette and mothers used a surgical
mask and careful hand and breast hygiene before breastfeeding and other interactions with the
infant.
• Two COVID-19 vaccines recently received FDA authorization through the Emergency Use
Authorization process, and additional vaccines are expected to become available soon. As often
occurs with new medications and vaccines, pregnant individuals were excluded from the clinical
trials for these vaccines. Results of animal studies on the first 2 vaccines authorized (Pfizer-
BioNTech and Moderna) are reassuring. Data on pregnancy outcomes of the small number of
pregnant individuals inadvertently exposed during the clinical trials are not yet available because
pregnancies are ongoing. Nearly all vaccines are allowed during pregnancy if the benefits are
expected to outweigh potential risks, with the exception of live-attenuated vaccines (such as the
measles-mumps-rubella [MMR] vaccine), which are contraindicated because of theoretical risks of

29. • The first 2 authorized COVID-19 vaccines use messenger RNA (mRNA) technology; mRNA
codes for the spike protein on the virus’s surface, which is then recognized by the host
immune system. The mRNA is rapidly degraded in the cell cytoplasm. These mRNA vaccines
(and other COVID-19 vaccine candidates) do not contain live virus. Thus, CDC, American
College of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal
Medicine (SMFM) state that pregnant individuals who meet criteria for receiving COVID-19
vaccine may choose to be vaccinated (Table).
• Pregnant individuals considering COVID-19 vaccination may benefit from a discussion with
their physician or other health care professional to weigh the benefits and potential risks of
vaccination. However, this discussion should be optional so that it does not impose a barrier
to vaccine receipt. Issues to consider in that discussion include data from animal studies and
on pregnant individuals who were inadvertently exposed during vaccine clinical trials (once
these data become available), risks of vaccine reactogenicity (eg, fever), timing of vaccination
by trimester, evidence for safety of other vaccines, potential for mitigation of SARS-CoV-2
exposure risk (eg, working from home), risk of COVID-19 to the fetus or newborn, and the
individual’s risk of complications due to pregnancy, her age, and underlying
conditions. Studies to examine the effects of COVID-19 vaccines during pregnancy are in
progress. For persons planning pregnancy, there is no evidence nor theoretical concerns
regarding effects of COVID-19 vaccines on fertility. It is not necessary to delay pregnancy

31. • Data on the effects of COVID-19 vaccines on the breastfed
infant are also unavailable. However, CDC, ACOG, and SMFM
are all reassuring about initiating or continuing breastfeeding
in a recently vaccinated individual, given the benefits of
breastfeeding to the infant and what is known about the safety
of other vaccines given during lactation.
• In the last year much has been learned about the effects of
COVID-19 on persons who are pregnant or postpartum;
however, many questions remain. Clinicians will need to follow
updates from CDC, ACOG, and SMFM for the latest information
related to COVID-19 during pregnancy and approaches for
prevention and treatment.

32. ARE COVID-19 VACCINES SAFE IN PREGNANCY?
VICTORIA MALE
NATURE REVIEWS IMMUNOLOGY VOLUME 21, PAGES200–201 (2021)
PUBLISHED: 03 MARCH 2021
• As the COVID-19 vaccination programme starts to be rolled
out, many young women are hesitant to accept the vaccine,
citing concerns about fertility. Meanwhile, those offered the
vaccine during pregnancy must decide whether they will accept,
even though pregnant people were excluded from the clinical
trials. Data on accidental pregnancies that occurred during the
trials and, increasingly, outcomes in pregnant people who
receive the vaccine can help these groups to make informed
decisions.

33. • In December 2020, a blog post appeared online claiming, falsely, that a
senior employee at Pfizer was concerned that antibodies elicited by COVID-
19 vaccines could attack the placenta. The post was quickly removed but the
rumours that it started continue to spread and a survey carried out by ‘Find
Out Now’ found that more than a quarter of young women in the United
Kingdom would decline the vaccine, citing concerns about its effect on
fertility. This is not the first time that unfounded rumours about vaccines
causing infertility have circulated. In 2003, such concerns resulted in a
boycott of polio vaccination in northern Nigeria; more recently, they have
contributed to hesitance in accepting the human papillomavirus vaccine. It is
understandable that people are apprehensive, especially about a new
vaccine: the vast majority of adverse events can be ruled out in clinical
trials, but the short time frame during which these take place, especially for
COVID-19, means that events that could potentially occur decades into the
future are harder to discount. Indeed, many people are hesitant specifically
about receiving an mRNA vaccine, as this is a relatively new platform. With
respect to these concerns, it is worth noting that the first human trials of
mRNA vaccines began in 2006, so there have been 15 years during which
any long-term problems arising from the platform itself could have come to
light.

34. • Although many of the rumours that COVID-19 vaccines might
damage fertility centre specifically on the mRNA platform, probably
because they first emerged in the context of the Pfizer/BioNTech
vaccine, the specific claim is that antibodies recognizing the SARS-
CoV-2 spike protein can cross-react with the human placental
protein syncytin 1 and thereby damage the placenta. If such cross-
reactivity did occur, vaccines on all platforms, as well as natural
infections, would be expected to be associated with placental
pathology. A natural experiment assures us that this is unlikely to be
the case as people who are infected with SARS-CoV-2 shortly before
conceiving or early in pregnancy are no more likely to miscarry than
their uninfected peers. Nonetheless, immunologists have also taken
formal approaches to address the claim that antibodies to spike
protein could cross-react with syncytin 1: there is no significant
similarity between the amino acid sequences of SARS-CoV-2 spike
protein and syncytin 1 and convalescent serum from patients with
COVID-19 does not react with syncytin 1.

35. • But the data that speak most clearly to the question of whether the COVID-19
vaccines harm fertility come from the clinical trials themselves. Developmental and
reproductive toxicity studies show that the vaccines do not prevent female rodents
becoming pregnant or harm the pups if given during pregnancy. We also have an idea
of how the vaccines affect pregnancy in humans from the volunteers who became
pregnant during the clinical trials. Pregnant people were excluded from the trials and
participants were asked to avoid becoming pregnant, but, nonetheless, 57
pregnancies occurred across the trials of the three vaccines that have so far been
approved in the UK.. There was no significant difference in the rate of accidental
pregnancies in the vaccinated groups compared with the control groups, which
indicates that the vaccines do not prevent pregnancy in humans. Similarly, the
miscarriage rates are comparable between the groups, indicating no detrimental
effect of vaccination on early pregnancy.
• Although the data are sparse, they are so far reassuring. For this reason, regulatory
bodies in the United Kingdom, European Union and United States have recommended
that pregnant people should be offered the vaccine where the benefits outweigh the
potential risks: pregnant workers on the frontline and those with pre-existing
conditions are now receiving the vaccine. In the United States, by 10 February 2021,

36. • In addition to widespread monitoring of vaccine recipients, formal studies
following the outcomes for cohorts of pregnant people who receive the vaccine
are underway. These are designed primarily to ensure safety and efficacy but will
also address the possibility that vaccination against COVID-19 is particularly
beneficial in pregnancy. Pregnant patients with COVID-19 are more likely to
need intensive care, it is more likely that doctors will elect to deliver their babies
early and their babies are also more likely to be admitted to the neonatal unit. It
is plausible that vaccination will reduce these risks and, should this be the case,
we should consider prioritizing pregnant people for vaccination.
• Further work will also address questions around whether vaccination during
pregnancy has any effect on the baby. These studies will, of course, aim to rule
out any detrimental effects, but many of the expected effects are beneficial. One
case study found anti-spike IgG in a newborn whose mother had received the
vaccine during pregnancy: does this occur widely and, if so, does antibody
transferred across the placenta endow the infant with any protection against
SARS-CoV-2 infection or COVID-19? Similarly, work is underway to determine
the extent to which vaccine-elicited antibodies to spike protein enter breast milk
and whether this has any protective effect for breast-fed infants.

37. • So, is COVID-19 vaccination safe during
pregnancy? The data so far suggest that it
is and, given the increased risks
associated with COVID-19 in pregnancy,
many pregnant people have decided to
accept the vaccine. By monitoring the
outcomes for these people and their
babies, we will soon be able to make
evidence-based recommendations on
whether the vaccines should be rolled out
to pregnant people more widely. In the
meantime, those who are planning
pregnancies can rest assured that multiple
strands of evidence show that vaccination