You are on page 1of 3

Case Report

Severe Acute Respiratory Teaching Points

Syndrome Coronavirus 2 1. Pregnant patients have been excluded from SARS-


CoV-2 vaccine trials, leading to uncertainty regarding
(SARS-CoV-2) Antibodies in safety, efficacy, and potential for neonatal passive
immunity.
Neonatal Cord Blood After 2. Vaccination in pregnancy produced a robust immune
response for the patient, with subsequent transpla-
Vaccination in Pregnancy cental transfer of neutralizing antibodies.

Lisa Gill, MD, MS,


Downloaded from http://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 10/29/2021

and Cresta W. Jones, MD mRNA vaccines have shown them to be safe and
effective in nonpregnant adults.1,2 Importantly, preg-
BACKGROUND: Studies evaluating the safety and effi- nant and lactating individuals were excluded from
cacy of currently available vaccines for severe acute initial safety and efficacy trials, despite data demon-
respiratory syndrome coronavirus 2 (SARS-CoV-2) do strating higher risks of severe infection and
not include pregnant participants. No data are available pregnancy-related morbidity and mortality.3 The
to counsel on vaccine safety and potential for neonatal American College of Obstetricians and Gynecologists
passive immunity. and the Society for Maternal-Fetal Medicine released
CASE: A 34-year-old multigravid patient working in a joint statement in January 2021 advocating that
health care received the Pfizer-BioNTech (BNT162b2) pregnant individuals at high risk for contracting the
mRNA vaccine for SARS-CoV-2 in the third trimester of virus should be able to decide whether they will
pregnancy. Uncomplicated spontaneous vaginal delivery receive the vaccination during pregnancy or while
of a female neonate with Apgar scores of 9 and 9 breastfeeding.4
occurred at term. The patient’s blood as well as neonatal In addition to safety, the potential for transplacental
cord blood were evaluated for SARS-CoV-2–specific transfer of neutralizing maternal antibodies is also a
antibodies. Both the patient and the neonate were pos-
consideration. The neonatal period is marked by an
itive for antibodies at a titer of 1:25,600.
immature immune system, making it a vulnerable period
CONCLUSION: In this case, passage of transplacental for infection. Maternal antibodies generated during
antibodies for SARS-CoV-2 was shown after vaccination pregnancy are able to cross the placenta into the fetal
in the third trimester of pregnancy. circulation, providing immune protection for the neo-
(Obstet Gynecol 2021;137:894–6)
nate. This has been demonstrated previously in pregnant
DOI: 10.1097/AOG.0000000000004367
patients receiving several other vaccines in pregnancy.4–7

N
In this case, we report on a pregnant individual
ewly available vaccines for severe acute respira-
who received the Pfizer-BioNTech (BNT162b2)
tory syndrome coronavirus 2 (SARS-CoV-2) are
mRNA vaccine for SARS-CoV-2 at 32 weeks of
of great interest to patients and health care profes-
gestation, with documented antibodies present in
sionals. Initial studies of the two currently available
neonatal cord blood.

From the Department of Obstetrics, Gynecology and Women’s Health, Division CASE
of Maternal-Fetal Medicine, University of Minnesota, Minneapolis, Minnesota.
Each author has confirmed compliance with the journal’s requirements for We present the case of a 34-year-old multigravid patient
authorship. (G4P2012) who works as a nurse in a large health care
Published online ahead-of-print March 8, 2021. system. System guidance allowed for pregnant individuals
Corresponding author: Lisa Gill, MD, MS, Department of Obstetrics, Gynecol-
to opt in to receive a vaccine when it was available based
ogy and Women’s Health, Division of Maternal-Fetal Medicine, University of on the tier system established by the Centers for Disease
Minnesota, Minneapolis, MN; email: lgill@umn.edu. Control and Prevention. The patient’s pregnancy was com-
Financial Disclosure plicated by a history of fetal growth restriction in both prior
The authors did not report any potential conflicts of interest. pregnancies and hemolysis, elevated liver enzymes, low
© 2021 by the American College of Obstetricians and Gynecologists. Published platelet count (HELLP) syndrome in one prior pregnancy.
by Wolters Kluwer Health, Inc. All rights reserved. Fetal growth was monitored by ultrasonography and was
ISSN: 0029-7844/21 normal throughout the pregnancy.

894 VOL. 137, NO. 5, MAY 2021 OBSTETRICS & GYNECOLOGY

© 2021 by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Vaccination became available when the patient was at blood”). No apparent complications were noted in
32 weeks of gestation. She received her first dose of the the patient or the neonate.
BNT162b2 mRNA vaccine at 32 6/7 weeks of gestation and Antibody transfer after vaccination in pregnancy
her second dose at 35 2/7 weeks. She reported no adverse ideally would confer protection for both the pregnant
effects from vaccine administration, with the exception of
patient and the neonate. Studies evaluating the neo-
soreness at the injection site.
natal immune response to maternal vaccine adminis-
The patient presented in spontaneous labor at 38 6/7
weeks of gestation. She underwent an unmedicated vaginal tration have demonstrated neonatal protection from
delivery without complication. The newborn course was transplacental antibody transfer for a number of
also uncomplicated—the neonate had Apgar scores of 9 vaccines, including tetanus toxoid, reduced diphtheria
and 9 at 1 and 5 minutes, and weight was appropriate for toxoid, and acellular pertussis (TDaP); influenza virus;
gestational age. Cord blood and maternal blood were ob- and respiratory syncytial virus.6–9 Our case supports
tained and evaluated for the presence of antibodies to that this may also be true for the SARS-CoV-2 vac-
SARS-CoV-2. Maternal blood was positive for immunoglob- cine. Although it is possible that neonatal antibodies
ulin G at a titer of 1:25,600. The cord blood was also were from undetected maternal infection with SARS-
positive for SARS-CoV-2–specific immunoglobulin G at a CoV-2, this is unlikely given the frequency and high
titer of 1:25,600.
sensitivity of polymerase chain reaction testing in this
In the course of her pregnancy, the patient was tested for
case.
SARS-CoV-2 infection multiple times by polymerase chain
reaction nasal swab. The patient received testing when Transplacental passage of SARS-CoV-2 anti-
experiencing any upper respiratory symptoms, occasional bodies after infection in pregnancy has been reported.
asymptomatic surveillance testing, and testing on admis- A recent study evaluating the vertical transmission of
sion for delivery. She reported no known SARS-CoV-2 SARS-CoV-2 as well as transplacental passage of
exposures. All test results were negative for the presence antibodies after infection in pregnancy showed low
of SARS-CoV-2 during her pregnancy. A prior antibody test rates of vertical transmission of the virus and also low
was performed as part of a system-wide effort to determine rates of transplacental antibody transfer. The authors
the incidence of infections among health care profes- conclude that this low rate of antibody transfer may
sionals, and the results were negative. Table 1 reviews all leave neonates susceptible to infection.5 Our case sug-
test results for the patient and the neonate.
gests that a more robust immune response may be
achieved after maternal vaccination than after natural
DISCUSSION infection with SARS-CoV-2. A prospective trial is cur-
To our knowledge, this is the first case report rently planned at our institution to compare neonatal
documenting transplacental transfer of neutralizing immune responses in populations of vaccinated preg-
SARS-CoV-2 antibodies in the setting of maternal nant people and pregnant people with SARS-CoV-2
mRNA vaccine administration (PubMed search con- infection.
ducted on February 12, 2021, with the following Importantly, data surrounding vaccines are fre-
search terms: “SARS-CoV-2 vaccine in pregnancy” quently generated with the exclusion of pregnant
or “COVID-19” or “SARS-CoV-2 vaccine in cord patients. Although pregnancy imparts many ethical

Table 1. Evaluations for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Sample Source Timing of Test (wk of Gestation) Test Result

Maternal Prepregnancy SARS-CoV-2 IgG Negative


Maternal 4 3/7 SARS-CoV-2 RNA RT-PCR Negative
Maternal 11 4/7 SARS-CoV-2 RNA RT-PCR Negative
Maternal 17 2/7 SARS-CoV-2 RNA RT-PCR Negative
Maternal 26 4/7 SARS-CoV-2 RNA RT-PCR Negative
Maternal 27 2/7 SARS-CoV-2 RNA RT-PCR Negative
Maternal 28 2/7 SARS-CoV-2 RNA RT-PCR Negative
Maternal 38 6/7 SARS-CoV-2 RNA RT-PCR Negative
SARS-CoV-2 IgG Positive
Titer 1:25,600*
Neonatal umbilical venous blood At birth SARS-CoV-2 IgG Positive
Titer 1:25,600
IgG, immunoglobulin G; PCR, polymerase chain reaction.
* Maternal vaccination occurred at 32 6/7 weeks of gestation (first dose) and 35 2/7 weeks of gestation (second dose).

VOL. 137, NO. 5, MAY 2021 Gill and Jones Neonatal SARS-CoV-2 Antibodies 895

© 2021 by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
dilemmas, the ability of pregnant patients to consent transplacental antibody transfer, and placental pathology in preg-
to participate in a clinical trial is not one of them. nancies during the COVID-19 pandemic. JAMA Netw Open
2020;3:e2030455. doi: 10.1001/jamanetworkopen.2020.30455
Recently, many experts have advocated for the
6. Quach THT, Mallis NA, Cordero JF. Influenza vaccine efficacy
inclusion of pregnant patients in clinical research in
and effectiveness in pregnant women: systematic review and
which the results may be useful in a pregnant meta-analysis. Matern Child Health J 2019;24:229–40. doi:
population.10–12 However, Smith et al13 found that 10.1007/s10995-019-02844-y
fewer than 2% of coronavirus disease 2019 (COV- 7. Cunningham W, Geard N, Felding JE, Braat S, Madhi SA,
ID-19) clinical trials listed on international registries Nunes MC, et al. Optimal timing of influenza vaccine during
included pregnant patients. Given this lack of data, pregnancy: a systematic review and meta-analysis. Influenza
Other Respir Viruses 2019;13:439–52. doi: 10.1111/irv.12649
there is understandable confusion over whether preg-
nant people should be vaccinated. Additional evi- 8. Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA,
Swamy GK, et al. Safety and immunogenicity of tetanus diph-
dence related to transplacental antibody transfer, as theria and acellular pertussis (Tdap) immunization during preg-
well as other risks and benefits of SARS-CoV-2 vac- nancy in mothers and infants. JAMA 2014;311:1760–9. doi: 10.
cination in pregnancy, will allow patients to make 1001/jama.2014.3633
informed choices regarding vaccination. Inclusion of 9. Mahdi S, Polack FP, Piedra PA, Munoz FM, Trenholme AA,
pregnant people in future clinical studies is critical. Simoes EAF, et al. Respiratory syncytial virus vaccination dur-
ing pregnancy and effects in infants. N Engl J Med 2020;383:
426–39. doi: 10.1056/NEJMoa1908380
REFERENCES
10. Spong CY, Bianchi DW. Improving public health requires
1. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R,
et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. inclusion of underrepresented populations in research. JAMA
N Engl J Med 2021;384:403–16. doi: 10.1056/NEJMoa2035389 2018;319:337–8. doi: 10.1001/jama.2017.19138
2. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lock- 11. Goldkind SF, Sahin L, Gallauresi B. Enrolling pregnant women
hart S, et al. Safety and efficacy of the BNT162b2 mRNA in research—lessons from the H1N1 influenza pandemic. N Engl
Covid-19 vaccine. N Engl J Med 2020;338:2603–15. doi: 10. J Med 2010;362:2241–3. doi: 10.1056/NEJMp1003462
1056/NEJMoa2034577 12. Macklin R. Enrolling pregnant women in biomedical research.
3. Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Lancet 2010;375:632–3. doi: 10.1016/s0140-6736(10)60257-7
Zambrano LD, et al. Characteristics of women of reproductive 13. Smith DD, Pippen JL, Adesomo AA, Rood KM, Landon MB,
age with laboratory-confirmed SARS-CoV-2 infection by preg-
Costantine MM. Exclusion of pregnant women from clinical
nancy status - United States, January 22–June 7, 2020. MMWR
Morb Mortal Wkly Rep 2020;69:769–75. doi: 10. trials during the coronavirus disease 2019 pandemic: a review
15585/mmwr.mm6925a1 of international registries. Am J Perinatol 2020;37:792–9. doi:
10.1055/s-0040-1712103
4. American College of Obstetricians and Gynecologists, Society
for Maternal-Fetal Medicine. ACOG and SMFM joint statement
on WHO recommendations regarding COVID-19 vaccines and
pregnant individuals. Accessed February 14, 2021. https://s3.am- PEER REVIEW HISTORY
azonaws.com/cdn.smfm.org/media/2726/WHO_Response.pdf Received February 14, 2021. Received in revised form February 23,
5. Edlow AG, Li JZ, Collier AY, Atyeo C, James KE, Boatin AA, 2021. Accepted February 24, 2021. Peer reviews and author corre-
et al. Assessment of maternal and neonatal SARS-CoV-2 viral load, spondence are available at http://links.lww.com/AOG/C254.

896 Gill and Jones Neonatal SARS-CoV-2 Antibodies OBSTETRICS & GYNECOLOGY

© 2021 by the American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.

You might also like