The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations

Irene A. Stafford; Jacqueline G. Parchem; Baha M. Sibai

doi:10.1016/j.ajog.2021.01.022

Clinical Opinion| Volume 224, ISSUE 5, P484-495, May 2021

The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations

Irene A. Stafford, MD
Irene A. Stafford
Correspondence
Corresponding author: Irene A. Stafford, MD.
Contact
Affiliations
Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
Search for articles by this author
Jacqueline G. Parchem, MD
Jacqueline G. Parchem
Affiliations
Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
Search for articles by this author
Baha M. Sibai, MD
Baha M. Sibai
Affiliations
Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
Search for articles by this author

Published:January 30, 2021DOI:https://doi.org/10.1016/j.ajog.2021.01.022

The coronavirus disease 2019 has caused over 2 million deaths worldwide, with over 412,000 deaths reported in Unites States. To date, at least 57,786 pregnant women in the United States have been infected, and 71 pregnant women have died. Although pregnant women are at higher risk of severe coronavirus disease 2019–related illness, clinical trials for the available vaccines excluded pregnant and lactating women. The safety and efficacy of the vaccines for pregnant women, the fetus, and the newborn remain unknown. A review of maternal and neonatal coronavirus disease 2019 morbidity and mortality data along with perinatal vaccine safety considerations are presented to assist providers with shared decision-making regarding vaccine administration for this group, including the healthcare worker who is pregnant, lactating, or considering pregnancy. The coronavirus disease 2019 vaccine should be offered to pregnant women after discussing the lack of safety data, with preferential administration for those at highest risk of severe infection, until safety and efficacy of these novel vaccines are validated.

Key words

The Coronavirus Disease 2019 Vaccine During Pregnancy: Risks, Benefits, and Recommendations

The current coronavirus disease 2019 vaccines

As of January 23, 2021, over 98 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported worldwide. In the United States, over 24 million people have been infected and at least 400,000 people have died because of SARS-CoV-2 infection.

¹

Centers for Disease control and Prevention
A weekly surveillance summary of U.S. COVID-19 activity.

Google Scholar

^,

²

Centers for Disease control and Prevention
Demographic Trends of COVID-19 cases and deaths in the US reported to CDC.

Google Scholar

^,

³

World Health Organization
Coronavirus disease (COVID-19) pandemic.

Google Scholar

^,

⁴

Woolf S.H.
Chapman D.A.
Sabo R.T.
Weinberger D.M.
Hill L.
Taylor D.D.H.

Excess deaths from COVID-19 and other causes, March-July 2020.

The pressing need for therapeutics and vaccines to treat and prevent coronavirus disease 2019 (COVID-19)-related illness and its effect on our global economic structure resulted in multiple research studies seeking effective tools to combat this disease.

⁵

Pascarella G.
Strumia A.
Piliego C.
et al.

COVID-19 diagnosis and management: a comprehensive review.

^,

⁶

Williamson E.J.
Walker A.J.
Bhaskaran K.
et al.

Factors associated with COVID-19-related death using OpenSAFELY.

^,

⁷

Cunningham J.W.
Vaduganathan M.
Claggett B.L.
et al.

Clinical outcomes in young US adults hospitalized with COVID-19.

^,

⁸

Faust J.S.
Krumholz H.M.
Du C.
et al.

All-cause excess mortality and COVID-19-related mortality among US adults aged 25-44 years, March-July 2020.

^,

⁹

U.S. Department of Health and Human Services
COVID-19 vaccines.

Google Scholar

^,

¹⁰

McDougle L.

Ensuring safety of operation warp speed vaccines for COVID-19.

^,

¹¹

Slaoui M.
Hepburn M.

Developing safe and effective covid vaccines - operation warp speed’s strategy and approach.

^,

¹²

Ho R.J.Y.

Warp-speed Covid-19 vaccine development: beneficiaries of maturation in biopharmaceutical technologies and public-private partnerships.

With the support of the US Department of Health and Human Services (DHHS), multiple researchers and pharmaceutical companies are actively pursuing the development and manufacture of efficacious and timely vaccines against this virus.

⁵

Pascarella G.
Strumia A.
Piliego C.
et al.

COVID-19 diagnosis and management: a comprehensive review.

^,

⁶

Williamson E.J.
Walker A.J.
Bhaskaran K.
et al.

Factors associated with COVID-19-related death using OpenSAFELY.

^,

⁷

Cunningham J.W.
Vaduganathan M.
Claggett B.L.
et al.

Clinical outcomes in young US adults hospitalized with COVID-19.

^,

⁸

Faust J.S.
Krumholz H.M.
Du C.
et al.

All-cause excess mortality and COVID-19-related mortality among US adults aged 25-44 years, March-July 2020.

^,

⁹

U.S. Department of Health and Human Services
COVID-19 vaccines.

Google Scholar

^,

¹⁰

McDougle L.

Ensuring safety of operation warp speed vaccines for COVID-19.

^,

¹¹

Slaoui M.
Hepburn M.

Developing safe and effective covid vaccines - operation warp speed’s strategy and approach.

^,

¹²

Ho R.J.Y.

Warp-speed Covid-19 vaccine development: beneficiaries of maturation in biopharmaceutical technologies and public-private partnerships.

On December 11, 2020, the Federal Drug Administration (FDA) issued the first Emergency Use Authorization (EUA) for Pfizer-BioNTech’s mRNA COVID-19 vaccine.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

This allowed the vaccine to be nationally distributed to adults aged ≥16 years using the safety and efficacy data from their global trial.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

Vaccine efficacy was demonstrated to be 95% in preventing symptomatic and laboratory-confirmed COVID-19 among persons without evidence of previous infection for 7 days after the second dose was administered.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

Shortly after, on December 18, 2020, Moderna, Inc, was issued an EUA after the safety and immunogenicity of their mRNA SARS-CoV-2 vaccine data were published and efficacy was demonstrated to be 94.1% against symptomatic and laboratory-confirmed infection in participants aged ≥18 years without evidence of previous infection for 14 days after completion of the 2-dose series.

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

Although not yet approved in the United States, the Oxford-AstraZeneca vaccine was approved by the British Department of Health and Social Care in the United Kingdom on December 30, 2020 after the vaccine was shown to have a pooled efficacy of 70.4% in preventing symptomatic and laboratory-confirmed COVID-19 14 days after completion of the 2-dose series among adults without previous infection.

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

Detailed summary data for the approved SARS-CoV-2 vaccines are presented in Table 1. On December 13, 2020, and December, 20, 2020, the Advisory Committee on Immunization Practices (ACIP) branch of the Centers for Disease Control and Prevention (CDC) issued an interim recommendation for use of the Pfizer-BioNTech and Moderna COVID-19 vaccines, respectively, after the designated COVID-19 working group reviewed the evidence for vaccine efficacy and safety and implementation considerations, including offering them to eligible pregnant and lactating women, despite their exclusion from these clinical trials.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

^,

²⁴

LaCourse S.
John-Stewart G.
Adams Waldorf K.M.

Importance of inclusion of pregnant and breastfeeding women in COVID-19 therapeutic trials.

Table 1Summary of available SAR-CoV-2 vaccines

Name	Vaccine type	Experimental design	Primary outcome	Secondary	Results
Pfizer-BioNTech	mRNA BNT162b2	Double-blinded RCT 1:1 ratio of vaccine to placebo	Efficacy against COVID-19 >7 d after second dose defined by:	1) Severe COVID-19 ^d Severe COVID-19 as defined by the FDA includes severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction; admission to the intensive care unit; or death	1) Without previous COVID-19: 95.0% efficacy (95% CI, 90.3–97.6)
		2 doses, 21 d apart	a) Symptomatic ^a Pfizer: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting	2) Safety or side effects	2) With or without previous COVID-19: 94.6% efficacy (95% CI, 89.9–97.3)
		≥16 y old	b) NAAT	3) Efficacy after first dose	3) Systemic complaints: first dose, 52%–59%; second dose, 39%–51%
		N=43,448	within 4 days of symptom onset ^b Respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-CoV-2 by nucleic acid amplification-based testing	4) In persons with or without COVID-19
		Multicenter, international	In persons without previous COVID-19 ^c Participants were assessed for the presence of SARS-CoV-2–binding antibodies specific to the SARS-CoV-2 nucleocapsid protein and had a nasopharyngeal swab for SARS-CoV-2 RT-PCR testing using protocol-defined acceptable tests
		Probability of vaccine efficacy >30%
		95.0% credible interval for vaccine efficacy
		Bayesian beta-binomial mode
Moderna	mRNA-1273	Observer-blinded RCT 1:1 ratio of vaccine to placebo	Efficacy against COVID-19 >14 d after second dose defined by:	1) Severe COVID-19 ^d Severe COVID-19 as defined by the FDA includes severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction; admission to the intensive care unit; or death	1) Without previous COVID-19: 94.1% efficacy (95% CI, 89.3–96.8)
		2 doses, 28 d apart	a) Symptomatic ^e Moderna: 2 or more the following symptoms: fever (temperature of ≥38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder or occurring in those who had at least 1 respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia)	2) Safety or side effects	2) In persons with previous COVID-19: 93.6% (95% CI, 88.6–96.5)
		≥18 y old	b) NAAT	3) Efficacy after first dose	3) Systemic complaints: first dose, 54.9%; second dose, 79.4%
		N=30,420	within 4 days of symptom onset ^f One NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR	4) In persons with and without previous COVID-19
		Multicenter, United States	In persons without previous COVID-19 ^c Participants were assessed for the presence of SARS-CoV-2–binding antibodies specific to the SARS-CoV-2 nucleocapsid protein and had a nasopharyngeal swab for SARS-CoV-2 RT-PCR testing using protocol-defined acceptable tests
		Probability of vaccine efficacy >30%
		1-sided O’Brien-Fleming boundary for efficacy. Lan-DeMets alpha-spending for efficacy boundaries
Oxford-AstraZeneca	Adenovirus-vectored vaccine	Single-blind and double-blind (1 site) RCT 1:1 ratio of vaccine to placebo 28 d apart	Efficacy against COVID-19 >14 d after second dose defined by:	1) Efficacy after both doses, full dose	1) Persons without previous COVID-19: vaccine efficacy: 90.0% (67.4–97.0) for 0.5 and full dose
		Subset: 0.5 and full dose second dose	a) Symptomatic ^g AstraZeneca: temperature of >37.8°C, cough, shortness of breath, and anosmia or ageusia. In some sites, the list of qualifying symptoms for swabbing was broader and included myalgia, chills, sore throat, headache, nasal congestion, diarrhea, runny nose, fatigue, nausea, vomiting, and loss of appetite	2) Safety or side effects	2) Vaccine efficacy: 62.1% (95% CI, 41.0–75.7) 2 full doses
		≥18 y old	b) NAAT ^h One NP swab or nasal swab positive for SARS-CoV-2 by RT-PCR by home kits using protocol-defined acceptable tests.	3) Efficacy in patients with previous COVID-19	3) 1.6% severe side effects
		N=23,848	In persons without previous COVID-19 ^c Participants were assessed for the presence of SARS-CoV-2–binding antibodies specific to the SARS-CoV-2 nucleocapsid protein and had a nasopharyngeal swab for SARS-CoV-2 RT-PCR testing using protocol-defined acceptable tests
		Multicenter, international	Primary: efficacy after first dose is 0.5 dose
		Vaccine efficacy Poisson regression model adjusted for age	Excluded if NAAT is positive within 14 d after second dose

CI, confidence interval; COVID-19, coronavirus disease 2019; FDA, Food and Drug Administration; NAAT, Nucleic acid amplification-based test; NP, nasopharyngeal; RCT, randomized controlled trial; RT-PCR, reverse transcription-polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Stafford. The coronavirus disease 2019 vaccine in pregnancy. Am J Obstet Gynecol 2021.

a Pfizer: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting

b Respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-CoV-2 by nucleic acid amplification-based testing

c Participants were assessed for the presence of SARS-CoV-2–binding antibodies specific to the SARS-CoV-2 nucleocapsid protein and had a nasopharyngeal swab for SARS-CoV-2 RT-PCR testing using protocol-defined acceptable tests

d Severe COVID-19 as defined by the FDA includes severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction; admission to the intensive care unit; or death

e Moderna: 2 or more the following symptoms: fever (temperature of ≥38°C), chills, myalgia, headache, sore throat, or new olfactory or taste disorder or occurring in those who had at least 1 respiratory sign or symptom (including cough, shortness of breath, or clinical or radiographic evidence of pneumonia)

f One NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR

g AstraZeneca: temperature of >37.8°C, cough, shortness of breath, and anosmia or ageusia. In some sites, the list of qualifying symptoms for swabbing was broader and included myalgia, chills, sore throat, headache, nasal congestion, diarrhea, runny nose, fatigue, nausea, vomiting, and loss of appetite

h One NP swab or nasal swab positive for SARS-CoV-2 by RT-PCR by home kits using protocol-defined acceptable tests.

Open table in a new tab

Coronavirus disease 2019 in pregnancy

Mechanical and physiological alterations in pregnancy increase susceptibility to certain infections.

²⁵

Alberca R.W.
Pereira N.Z.
Oliveira L.M.D.S.
Gozzi-Silva S.C.
Sato M.N.

Pregnancy, viral infection, and COVID-19.

^,

²⁶

Yuen K.S.
Ye Z.W.
Fung S.Y.
Chan C.P.
Jin D.Y.

SARS-CoV-2 and COVID-19: the most important research questions.

^,

²⁷

Fung S.Y.
Yuen K.S.
Ye Z.W.
Chan C.P.
Jin D.Y.

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses.

The immunologic alterations that occur during pregnancy not only may be protective to the fetal allograft but also may create vulnerability to certain viral infections.

²⁵

Alberca R.W.
Pereira N.Z.
Oliveira L.M.D.S.
Gozzi-Silva S.C.
Sato M.N.

Pregnancy, viral infection, and COVID-19.

^,

²⁶

Yuen K.S.
Ye Z.W.
Fung S.Y.
Chan C.P.
Jin D.Y.

SARS-CoV-2 and COVID-19: the most important research questions.

^,

²⁷

Fung S.Y.
Yuen K.S.
Ye Z.W.
Chan C.P.
Jin D.Y.

A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses.

More than 1600 reports evaluating COVID-19 and pregnancy have been published. Most reports are cohort studies, case series, and meta-analyses describing diagnostic challenges, therapeutic options, intrauterine transmission, and perinatal complications among affected pregnancies. Although several studies, including a recent meta-analysis with data from over 435 pregnant women with infection have suggested that the severity of COVID-19 in pregnant women is similar to nonpregnant adults,

²⁸

Huntley B.J.F.
Huntley E.S.
Di Mascio D.
Chen T.
Berghella V.
Chauhan S.P.

Rates of maternal and perinatal mortality and vertical transmission in pregnancies complicated by severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) infection: a systematic review.

^,

²⁹

Adhikari E.H.
Moreno W.
Zofkie A.C.
et al.

Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection.

^,

³⁰

Handley S.C.
Mullin A.M.
Elovitz M.A.
et al.

Changes in preterm birth phenotypes and stillbirth at 2 Philadelphia hospitals during the SARS-CoV-2 pandemic, March-June 2020.

^,

³¹

Pineles B.L.
Alamo I.C.
Farooq N.
et al.

Racial-ethnic disparities and pregnancy outcomes in SARS-CoV-2 infection in a universally-tested cohort in Houston, Texas.

^,

³²

Ahlberg M.
Neovius M.
Saltvedt S.
et al.

Association of SARS-CoV-2 test status and pregnancy outcomes.

^,

³³

Pettirosso E.
Giles M.
Cole S.
Rees M.

COVID-19 and pregnancy: a review of clinical characteristics, obstetric outcomes and vertical transmission.

^,

³⁴

Di Mascio D.
Khalil A.
Saccone G.
et al.

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.

CDC data and other publications indicate an increased risk of intensive care unit (ICU) admission (10.5 vs 3.9 per 1000 cases; adjusted risk ratio [aRR], 3.0; 95% confidence interval [CI], 2.6–3.4), mechanical ventilation (2.9 vs 1.1 per 1000 cases; aRR, 2.9; 95% CI, 2.2–3.8), and death (1.5 vs 1.2 per 1000 cases; aRR, 1.7; 95% CI, 1.2–2.4) in pregnant patients with symptomatic COVID-19 infection compared with nonpregnant women after adjusting for age, race, ethnicity, and comorbidities, with even higher risk for subgroups of women who are underserved, have comorbidities, or are of advanced maternal age.

³⁵

DeBolt C.A.
Bianco A.
Limaye M.A.
et al.

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

^,

³⁶

Hantoushzadeh S.
Shamshirsaz A.A.
Aleyasin A.
et al.

Maternal death due to COVID-19.

^,

³⁷

Pierce-Williams R.A.M.
Burd J.
Felder L.
et al.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

^,

³⁸

Juan J.
Gil M.M.
Rong Z.
Zhang Y.
Yang H.
Poon L.C.

Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.

^,

³⁹

Dashraath P.
Wong J.L.J.
Lim M.X.K.
et al.

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

^,

⁴⁰

Knight M.
Bunch K.
Vousden N.
et al.

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

^,

⁴¹

Moore J.T.
Ricaldi J.N.
Rose C.E.
et al.

Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 states, February-June 2020.

^,

⁴²

Panagiotakopoulos L.
Myers T.R.
Gee J.
et al.

SARS-CoV-2 infection among hospitalized pregnant women: reasons for admission and pregnancy characteristics - eight U.S. health care centers, March 1-May 30, 2020.

^,

⁴³

Delahoy M.J.
Whitaker M.
O’Halloran A.
et al.

Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 - COVID-NET, 13 states, March 1-August 22, 2020.

^,

⁴⁴

Ellington S.
Strid P.
Tong V.T.
et al.

Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020.

^,

⁴⁵

Zambrano L.D.
Ellington S.
Strid P.
et al.

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.

However, these surveillance data have limitations, as over 64.5% of total cases involving women did not have pregnancy status recorded.

⁴⁵

Zambrano L.D.
Ellington S.
Strid P.
et al.

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.

In addition, among those with known pregnancy status, race and ethnicity status was missing for 25% of cases, and information on symptoms and underlying conditions was missing for approximately half of the participants.

⁴⁵

Zambrano L.D.
Ellington S.
Strid P.
et al.

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.

A recent publication of morbidity, mortality, and pregnancy outcome of over 400,000 women admitted for delivery with and without COVID-19 collected from an all-payer database of 20% of US hospitals demonstrated similar outcomes, reporting an increased rate of death in women with infection compared to those without COVID-19 (number of deaths per 100,000 women, 141 [95% CI, 65–268] vs 5.0 [95% CI, 3.1–7.7]).

⁴⁶

Jering K.S.
Claggett B.L.
Cunningham J.W.
et al.

Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19.

Despite limited evidence that the infection increases other adverse pregnancy outcomes, there remains a higher risk of thromboembolic disease, hypertensive disorders, preterm birth, and cesarean delivery for pregnant women with infection, differentially represented across global regions.

²⁸

Huntley B.J.F.
Huntley E.S.
Di Mascio D.
Chen T.
Berghella V.
Chauhan S.P.

Rates of maternal and perinatal mortality and vertical transmission in pregnancies complicated by severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) infection: a systematic review.

^,

²⁹

Adhikari E.H.
Moreno W.
Zofkie A.C.
et al.

Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection.

^,

³⁰

Handley S.C.
Mullin A.M.
Elovitz M.A.
et al.

Changes in preterm birth phenotypes and stillbirth at 2 Philadelphia hospitals during the SARS-CoV-2 pandemic, March-June 2020.

^,

³¹

Pineles B.L.
Alamo I.C.
Farooq N.
et al.

Racial-ethnic disparities and pregnancy outcomes in SARS-CoV-2 infection in a universally-tested cohort in Houston, Texas.

^,

³²

Ahlberg M.
Neovius M.
Saltvedt S.
et al.

Association of SARS-CoV-2 test status and pregnancy outcomes.

^,

³³

Pettirosso E.
Giles M.
Cole S.
Rees M.

COVID-19 and pregnancy: a review of clinical characteristics, obstetric outcomes and vertical transmission.

^,

³⁴

Di Mascio D.
Khalil A.
Saccone G.
et al.

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.

^,

³⁵

DeBolt C.A.
Bianco A.
Limaye M.A.
et al.

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

^,

³⁶

Hantoushzadeh S.
Shamshirsaz A.A.
Aleyasin A.
et al.

Maternal death due to COVID-19.

^,

³⁷

Pierce-Williams R.A.M.
Burd J.
Felder L.
et al.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

^,

³⁸

Juan J.
Gil M.M.
Rong Z.
Zhang Y.
Yang H.
Poon L.C.

Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.

^,

³⁹

Dashraath P.
Wong J.L.J.
Lim M.X.K.
et al.

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

^,

⁴⁰

Knight M.
Bunch K.
Vousden N.
et al.

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

^,

⁴¹

Moore J.T.
Ricaldi J.N.
Rose C.E.
et al.

Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 states, February-June 2020.

^,

⁴²

Panagiotakopoulos L.
Myers T.R.
Gee J.
et al.

SARS-CoV-2 infection among hospitalized pregnant women: reasons for admission and pregnancy characteristics - eight U.S. health care centers, March 1-May 30, 2020.

^,

⁴³

Delahoy M.J.
Whitaker M.
O’Halloran A.
et al.

Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 - COVID-NET, 13 states, March 1-August 22, 2020.

^,

⁴⁴

Ellington S.
Strid P.
Tong V.T.
et al.

Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020.

^,

⁴⁵

Zambrano L.D.
Ellington S.
Strid P.
et al.

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.

^,

⁴⁶

Jering K.S.
Claggett B.L.
Cunningham J.W.
et al.

Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19.

Although the absolute risk for severe infection is low, the CDC has included pregnancy as a risk factor for severe COVID-19, and this has been echoed by the Society for Maternal-Fetal Medicine (SMFM), the American College of Obstetricians and Gynecologists (ACOG), and other women’s health organizations.

⁴⁷

The American College of Obstetricians and Gynecologists
Vaccinating pregnant and lactating patients against COVID-19.

Google Scholar

^,

⁴⁸

Society for Maternal-Fetal Medicine (SMFM) Statement: SARS-Co-V-2 Vaccination in pregnancy. Available at: https://s3.amazonaws.com/cdn.smfm.org/media/2591/SMFM_Vaccine_Statement_12-1-20. Accessed Jan. 19, 2021

Google Scholar

^,

⁴⁹

Academy of Breastfeeding Medicine
Considerations for COVID-19 vaccination in lactation. ABM Statement.

Google Scholar

^,

⁵⁰

Centers for Disease Control and Prevention
COVID-19 (coronavirus disease): people with certain medical conditions.

Google Scholar

^,

⁵¹

Royal College of Obstetricians and Gynaecologists
Updated advice on COVID-19 vaccination in pregnancy and women who are breastfeeding.

Google Scholar

^,

⁵²

Advisory Committee on Immunization Practices (ACIP). ACIP recommendations.

Google Scholar

^,

⁵³

Dooling K.
Marin M.
Wallace M.
et al.

The Advisory Committee on Immunization Practices’ updated interim recommendation for allocation of COVID-19 vaccine - United States, December 2020.

Several reports of neonatal transmission and adverse outcomes for newborns with infection have been reported; however, some of these data are confounded by uncertainty surrounding testing and diagnostics for these neonates and other independent neonatal morbidities.

⁵⁴

Schwartz D.A.

An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes.

^,

⁵⁵

Flaherman V.J.
Afshar Y.
Boscardin J.
et al.

Infant outcomes following maternal infection with SARS-CoV-2: first report from the PRIORITY study.

^,

⁵⁶

Kotlyar A.M.
Grechukhina O.
Chen A.
et al.

Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.

^,

⁵⁷

Leung C.

Clinical characteristics of COVID-19 in children: are they similar to those of SARS?.

^,

⁵⁸

Edlow A.G.
Li J.Z.
Collier A.Y.
et al.

Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer, and placental pathology in pregnancies during the COVID-19 pandemic.

^,

⁵⁹

Dumitriu D.
Emeruwa U.N.
Hanft E.
et al.

Outcomes of neonates born to mothers with severe acute respiratory syndrome coronavirus 2 infection at a large medical center in New York City.

Google Scholar

^,

⁶⁰

Prabhu M.
Cagino K.
Matthews K.C.
et al.

Pregnancy and postpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: a prospective cohort study.

Collectively, the current available data suggest an approximate 2% to 3% risk of vertical transmission with a minimal rate of persistent neonatal infection. Consistent with these observations are data showing that SARS-CoV-2 is not routinely detected in amniotic fluid, cord blood, or neonatal nasopharyngeal samples associated with affected pregnancies.

⁵⁴

Schwartz D.A.

An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes.

^,

⁵⁵

Flaherman V.J.
Afshar Y.
Boscardin J.
et al.

Infant outcomes following maternal infection with SARS-CoV-2: first report from the PRIORITY study.

^,

⁵⁶

Kotlyar A.M.
Grechukhina O.
Chen A.
et al.

Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis.

^,

⁵⁷

Leung C.

Clinical characteristics of COVID-19 in children: are they similar to those of SARS?.

^,

⁵⁸

Edlow A.G.
Li J.Z.
Collier A.Y.
et al.

Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer, and placental pathology in pregnancies during the COVID-19 pandemic.

^,

⁵⁹

Dumitriu D.
Emeruwa U.N.
Hanft E.
et al.

Outcomes of neonates born to mothers with severe acute respiratory syndrome coronavirus 2 infection at a large medical center in New York City.

Google Scholar

^,

⁶⁰

Prabhu M.
Cagino K.
Matthews K.C.
et al.

Pregnancy and postpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: a prospective cohort study.

Several studies have described the detection of viral RNA in breast milk of mothers with infection; however, there is no evidence to suggest that the ingestion of breast milk from mothers with SAR-CoV-2 infection increases the risk of transmission to their newborns.

⁶¹

Groß R.
Conzelmann C.
Müller J.A.
et al.

Detection of SARS-CoV-2 in human breastmilk.

^,

⁶²

Chambers C.
Krogstad P.
Bertrand K.
et al.

Evaluation for SARS-CoV-2 in breast milk from 18 infected women.

^,

⁶³

Centeno-Tablante E.
Medina-Rivera M.
Finkelstein J.L.
et al.

Transmission of SARS-CoV-2 through breast milk and breastfeeding: a living systematic review.

Variable quantities of immunoglobulin A antibodies were detected in 80% of 18 breast milk samples collected from women with infection in 1 study; however, the protective capacity of these antibodies against infection for newborns and infants requires further investigation.

⁶¹

Groß R.
Conzelmann C.
Müller J.A.
et al.

Detection of SARS-CoV-2 in human breastmilk.

^,

⁶²

Chambers C.
Krogstad P.
Bertrand K.
et al.

Evaluation for SARS-CoV-2 in breast milk from 18 infected women.

^,

⁶³

Centeno-Tablante E.
Medina-Rivera M.
Finkelstein J.L.
et al.

Transmission of SARS-CoV-2 through breast milk and breastfeeding: a living systematic review.

Past pandemics and vaccine safety in pregnant women

Disproportionate rates of maternal morbidity, adverse perinatal outcomes, and mortality because of infectious disease have been described in past pandemics. During the 2002 severe acute respiratory syndrome (SARS) pandemic, which infected over 8000 people in 26 countries, maternal case fatality was 25%, and miscarriage occurred in 57% of pregnant women with infection.

⁶⁴

World Health Organization
Influenza (seasonal) factsheet.

Google Scholar

^,

⁶⁵

Centers for Disease Control and Prevention
Disease burden of influenza.

Google Scholar

^,

⁶⁶

Mead P.S.
Slutsker L.
Dietz V.
et al.

Food-related illness and death in the United States.

^,

⁶⁷

Shrestha S.S.
Swerdlow D.L.
Borse R.H.
et al.

Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010).

^,

⁶⁸

Katz M.A.
Gessner B.D.
Johnson J.
et al.

Incidence of influenza virus infection among pregnant women: a systematic review.

^,

⁶⁹

Siston A.M.
Rasmussen S.A.
Honein M.A.
et al.

Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States.

^,

⁷⁰

Creanga A.A.
Johnson T.F.
Graitcer S.B.
et al.

Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.

The Middle East respiratory syndrome, another coronavirus, has demonstrated similar pathogenicity, leading to adverse perinatal events in over 90% of women with infection in 2012.

⁶⁴

World Health Organization
Influenza (seasonal) factsheet.

Google Scholar

^,

⁶⁵

Centers for Disease Control and Prevention
Disease burden of influenza.

Google Scholar

^,

⁶⁶

Mead P.S.
Slutsker L.
Dietz V.
et al.

Food-related illness and death in the United States.

^,

⁶⁷

Shrestha S.S.
Swerdlow D.L.
Borse R.H.
et al.

Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010).

^,

⁶⁸

Katz M.A.
Gessner B.D.
Johnson J.
et al.

Incidence of influenza virus infection among pregnant women: a systematic review.

^,

⁶⁹

Siston A.M.
Rasmussen S.A.
Honein M.A.
et al.

Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States.

^,

⁷⁰

Creanga A.A.
Johnson T.F.
Graitcer S.B.
et al.

Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.

Currently, a safe and efficacious vaccine has not been developed for these pathogens. In 2009, a novel strain of the influenza A virus, termed H1N1, resulted in a pandemic with an estimated 40 million people infected between April 2009 and April 2010, resulting in more than 274,304 hospitalizations and 12,469 deaths.

⁶⁴

World Health Organization
Influenza (seasonal) factsheet.

Google Scholar

^,

⁶⁵

Centers for Disease Control and Prevention
Disease burden of influenza.

Google Scholar

^,

⁶⁶

Mead P.S.
Slutsker L.
Dietz V.
et al.

Food-related illness and death in the United States.

^,

⁶⁷

Shrestha S.S.
Swerdlow D.L.
Borse R.H.
et al.

Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010).

^,

⁶⁸

Katz M.A.
Gessner B.D.
Johnson J.
et al.

Incidence of influenza virus infection among pregnant women: a systematic review.

^,

⁶⁹

Siston A.M.
Rasmussen S.A.
Honein M.A.
et al.

Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States.

^,

⁷⁰

Creanga A.A.
Johnson T.F.
Graitcer S.B.
et al.

Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.

^,

⁷¹

Cox C.M.
Blanton L.
Dhara R.
Brammer L.
Finelli L.

2009 pandemic influenza A (H1N1) deaths among children--United States, 2009-2010.

^,

⁷²

Jain S.
Kamimoto L.
Bramley A.M.
et al.

Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009.

^,

⁷³

Skarbinski J.
Jain S.
Bramley A.
et al.

Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009.

^,

⁷⁴

Dulyachai W.
Makkoch J.
Rianthavorn P.
et al.

Perinatal pandemic (H1N1) 2009 infection, Thailand.

During the first 5 months of the H1N1 pandemic, 788 cases were reported in pregnant women. Of those cases, 30 pregnant women died, comprising 5% of all reported 2009 influenza H1N1 deaths during this period.

⁶⁷

Shrestha S.S.
Swerdlow D.L.
Borse R.H.
et al.

Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010).

^,

⁶⁸

Katz M.A.
Gessner B.D.
Johnson J.
et al.

Incidence of influenza virus infection among pregnant women: a systematic review.

^,

⁶⁹

Siston A.M.
Rasmussen S.A.
Honein M.A.
et al.

Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States.

^,

⁷⁰

Creanga A.A.
Johnson T.F.
Graitcer S.B.
et al.

Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.

^,

⁷¹

Cox C.M.
Blanton L.
Dhara R.
Brammer L.
Finelli L.

2009 pandemic influenza A (H1N1) deaths among children--United States, 2009-2010.

^,

⁷²

Jain S.
Kamimoto L.
Bramley A.M.
et al.

Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009.

^,

⁷³

Skarbinski J.
Jain S.
Bramley A.
et al.

Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009.

^,

⁷⁴

Dulyachai W.
Makkoch J.
Rianthavorn P.
et al.

Perinatal pandemic (H1N1) 2009 infection, Thailand.

Furthermore, 4 case reports of suspected H1N1 vertical transmission in newborns have been published, with 1 reported neonatal death.

⁷⁵

Valvi C.
Kulkarni R.
Kinikar A.
Khadse S.

2009H1N1 infection in a 1-day-old neonate.

^,

⁷⁶

Cetinkaya M.
Ozkan H.
Celebi S.
Köksal N.
Hacimustafaoğlu M.

Human 2009 influenza A (H1N1) virus infection in a premature infant born to an H1N1-infected mother: placental transmission?.

^,

⁷⁷

Vásquez R.D.
Chávez V.M.
Gamio I.E.
et al.

[Probable vertical transmission of the influenza virus A (H1N1): apropos of a case].

^,

⁷⁸

Yudin M.H.

Risk management of seasonal influenza during pregnancy: current perspectives.

In addition, observational studies have demonstrated higher frequencies of maternal infectious morbidity, showing higher rates of maternal ICU admission and death because of H1N1 influenza infection compared with rates in nonpregnant populations, even more so than the rates of the current COVID-19 pandemic.

⁷⁹

Mertz D.
Geraci J.
Winkup J.
Gessner B.D.
Ortiz J.R.
Loeb M.

Pregnancy as a risk factor for severe outcomes from influenza virus infection: a systematic review and meta-analysis of observational studies.

^,

⁸⁰

Mertz D.
Lo C.K.
Lytvyn L.
Ortiz J.R.
Loeb M.

FLURISK-INVESTIGATORS
Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis.

Vaccines and reproductive toxicology

Although several vaccine efficacy and safety studies were conducted with pregnant and lactating women during the H1N1 pandemic, the COVID-19 vaccine trials have excluded these groups, and therefore, critical perinatal safety information remains largely unknown.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

^,

²⁴

LaCourse S.
John-Stewart G.
Adams Waldorf K.M.

Importance of inclusion of pregnant and breastfeeding women in COVID-19 therapeutic trials.

^,

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

The mRNA (Pfizer-BioNTech and Moderna) and viral vector (AstraZeneca) COVID-19 vaccines are novel in design and, to date, are the first mRNA and viral vector vaccine trials to have been comprehensively evaluated for disease prevention in people.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

^,

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

Of note, the Ebola vaccine (rVSVΔG-ZEBOV-G, Merck) was developed using similar viral vector technology and is currently approved for disease prevention in nonpregnant adults.

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

Several preliminary human studies have demonstrated promising safety and immunogenicity data using the mRNA vaccine model with other pathogens, including the influenza virus, Zika virus, and rabies virus,

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

^,

⁸²

Maruggi G.
Zhang C.
Li J.
Ulmer J.B.
Yu D.

mRNA as a transformative technology for vaccine development to control infectious diseases.

^,

⁸³

Pardi N.
Hogan M.J.
Porter F.W.
Weissman D.

mRNA vaccines - a new era in vaccinology.

^,

⁸⁴

Zhang C.
Maruggi G.
Shan H.
Li J.

Advances in mRNA vaccines for infectious diseases.

^,

⁸⁵

Alberer M.
Gnad-Vogt U.
Hong H.S.
et al.

Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.

^,

⁸⁶

Feldman R.A.
Fuhr R.
Smolenov I.
et al.

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.

^,

⁸⁷

Richner J.M.
Himansu S.
Dowd K.A.
et al.

Modified mRNA vaccines protect against Zika virus infection.

^,

⁸⁸

Richner J.M.
Jagger B.W.
Shan C.
et al.

Vaccine mediated protection against Zika virus-induced congenital disease.

but previous efficacy studies evaluating mRNA vaccines during pregnancy are limited to animal studies involving the Zika virus, where vaccination resulted in a significant reduction of placental and fetal viral burden.

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

^,

⁸²

Maruggi G.
Zhang C.
Li J.
Ulmer J.B.
Yu D.

mRNA as a transformative technology for vaccine development to control infectious diseases.

^,

⁸³

Pardi N.
Hogan M.J.
Porter F.W.
Weissman D.

mRNA vaccines - a new era in vaccinology.

^,

⁸⁴

Zhang C.
Maruggi G.
Shan H.
Li J.

Advances in mRNA vaccines for infectious diseases.

^,

⁸⁵

Alberer M.
Gnad-Vogt U.
Hong H.S.
et al.

Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.

^,

⁸⁶

Feldman R.A.
Fuhr R.
Smolenov I.
et al.

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.

^,

⁸⁷

Richner J.M.
Himansu S.
Dowd K.A.
et al.

Modified mRNA vaccines protect against Zika virus infection.

^,

⁸⁸

Richner J.M.
Jagger B.W.
Shan C.
et al.

Vaccine mediated protection against Zika virus-induced congenital disease.

Details concerning transplacental vaccine transfer have not been described.

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

^,

⁸²

Maruggi G.
Zhang C.
Li J.
Ulmer J.B.
Yu D.

mRNA as a transformative technology for vaccine development to control infectious diseases.

^,

⁸³

Pardi N.
Hogan M.J.
Porter F.W.
Weissman D.

mRNA vaccines - a new era in vaccinology.

^,

⁸⁴

Zhang C.
Maruggi G.
Shan H.
Li J.

Advances in mRNA vaccines for infectious diseases.

^,

⁸⁵

Alberer M.
Gnad-Vogt U.
Hong H.S.
et al.

Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.

^,

⁸⁶

Feldman R.A.
Fuhr R.
Smolenov I.
et al.

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.

^,

⁸⁷

Richner J.M.
Himansu S.
Dowd K.A.
et al.

Modified mRNA vaccines protect against Zika virus infection.

^,

⁸⁸

Richner J.M.
Jagger B.W.
Shan C.
et al.

Vaccine mediated protection against Zika virus-induced congenital disease.

Although disclosed details of the protocols are available for review, the precise formulations of the cationic nanoparticles used for mRNA assembly of the COVID-19 vaccines remain propriety to the manufacturing pharmaceutical companies and preliminary safety data regarding the COVID-19 mRNA vaccines during gestation reference a perinatal or postnatal reproductive toxicology study in rats, which demonstrated no safety alert.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

^,

⁴⁷

The American College of Obstetricians and Gynecologists
Vaccinating pregnant and lactating patients against COVID-19.

Google Scholar

Ultimately, the advantage of past and present influenza vaccine designs in comparison is the background benefit of known published protocols and historic experience utilizing inactivated or attenuated virus since 1940, leading to a more expeditious design for safety and efficacy.

⁸⁹

Sakala I.G.
Honda-Okubo Y.
Fung J.
Petrovsky N.

Influenza immunization during pregnancy: benefits for mother and infant.

^,

⁹⁰

Blanchard-Rohner G.
Meier S.
Bel M.
et al.

Influenza vaccination given at least 2 weeks before delivery to pregnant women facilitates transmission of seroprotective influenza-specific antibodies to the newborn.

^,

⁹¹

Chao A.S.
Chang Y.L.
Chao A.
et al.

Seropositivity of influenza A H1NI in mothers and infants following maternal vaccination with trivalent seasonal influenza vaccine after the 2009 pandemic.

^,

⁹²

Keller-Stanislawski B.
Englund J.A.
Kang G.
et al.

Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

^,

⁹³

Donahue J.G.
Kieke B.A.
King J.P.
et al.

Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012-13, 2013-14, and 2014-15.

^,

⁹⁴

Quach T.H.T.
Mallis N.A.
Cordero J.F.

Influenza vaccine efficacy and effectiveness in pregnant women: systematic review and meta-analysis.

^,

⁹⁵

Takeda S.
Hisano M.
Komano J.
Yamamoto H.
Sago H.
Yamaguchi K.

Influenza vaccination during pregnancy and its usefulness to mothers and their young infants.

These studies were accomplished with fewer challenges compared with the de novo human vaccine development for the novel SARS-CoV-2.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

^,

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

Typically, vaccines intended for pregnant or breastfeeding women rely on critical review by the scientific community of all observational studies, case reports and series, registries and experimental data regarding the type of vaccine, pathogen placental transfer studies, toxicity and immunogenicity studies, and trimester-specific infection risks. These reviews are conducted through collaborative efforts by the Vaccine Safety Datalink, a collaborative project between the CDC and others, including the ACIP Workgroup, National Institutes of Health, Task Force on Research Specific to Pregnant Women and Lactating Women, World Health Organization, and Global Advisory Committee on Vaccine Safety.

¹⁰⁰

Newcomer S.R.
Daley M.F.
Narwaney K.J.
et al.

Order of live and inactivated vaccines and risk of nonvaccine-targeted infections in US children 11-23 months of age.

^,

⁸⁹

Sakala I.G.
Honda-Okubo Y.
Fung J.
Petrovsky N.

Influenza immunization during pregnancy: benefits for mother and infant.

^,

⁹⁰

Blanchard-Rohner G.
Meier S.
Bel M.
et al.

Influenza vaccination given at least 2 weeks before delivery to pregnant women facilitates transmission of seroprotective influenza-specific antibodies to the newborn.

^,

⁹¹

Chao A.S.
Chang Y.L.
Chao A.
et al.

Seropositivity of influenza A H1NI in mothers and infants following maternal vaccination with trivalent seasonal influenza vaccine after the 2009 pandemic.

^,

⁹²

Keller-Stanislawski B.
Englund J.A.
Kang G.
et al.

Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

^,

⁹³

Donahue J.G.
Kieke B.A.
King J.P.
et al.

Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012-13, 2013-14, and 2014-15.

^,

⁹⁴

Quach T.H.T.
Mallis N.A.
Cordero J.F.

Influenza vaccine efficacy and effectiveness in pregnant women: systematic review and meta-analysis.

^,

⁹⁵

Takeda S.
Hisano M.
Komano J.
Yamamoto H.
Sago H.
Yamaguchi K.

Influenza vaccination during pregnancy and its usefulness to mothers and their young infants.

^,

⁹⁶

McNeil M.M.
Gee J.
Weintraub E.S.
et al.

The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

^,

⁹⁷

Naleway A.L.
Gold R.
Kurosky S.
et al.

Identifying pregnancy episodes, outcomes, and mother-infant pairs in the Vaccine Safety Datalink.

^,

⁹⁸

Sejvar J.J.
Kohl K.S.
Gidudu J.
et al.

Brighton Collaboration GBS. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data.

^,

⁹⁹

Wang S.V.
Stefanini K.
Lewis E.
et al.

Determining which of several simultaneously administered vaccines increase risk of an adverse event.

Priority is granted to potential vaccines that meet several key criteria when considered for mass vaccination campaigns.

¹⁰⁰

Newcomer S.R.
Daley M.F.
Narwaney K.J.
et al.

Order of live and inactivated vaccines and risk of nonvaccine-targeted infections in US children 11-23 months of age.

^,

¹⁰¹

Glanz J.M.
Clarke C.L.
Xu S.
et al.

Association between rotavirus vaccination and type 1 diabetes in children.

^,

¹⁰²

Li R.
Stewart B.
Rose C.

A Bayesian approach to sequential analysis in post-licensure vaccine safety surveillance.

^,

¹⁰³

Yu W.
Zheng C.
Xie F.
et al.

The use of natural language processing to identify vaccine-related anaphylaxis at five health care systems in the Vaccine Safety Datalink.

^,

¹⁰⁴

Groom H.C.
Smith N.
Irving S.A.
et al.

Uptake and safety of hepatitis A vaccination during pregnancy: a Vaccine Safety Datalink study.

^,

¹⁰⁵

Myers T.R.
McCarthy N.L.
Panagiotakopoulos L.
Omer S.B.

Estimation of the incidence of Guillain-Barré syndrome during pregnancy in the United States.

^,

¹⁰⁶

Dudley M.Z.
Halsey N.A.
Omer S.B.
et al.

The state of vaccine safety science: systematic reviews of the evidence.

^,

¹⁰⁷

Kochhar S.

Communicating vaccine safety during the development and introduction of vaccines.

^,

¹⁰⁸

Fortner K.B.
Nieuwoudt C.
Reeder C.F.
Swamy G.K.

Infections in pregnancy and the role of vaccines.

^,

⁹⁶

McNeil M.M.
Gee J.
Weintraub E.S.
et al.

The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

^,

⁹⁷

Naleway A.L.
Gold R.
Kurosky S.
et al.

Identifying pregnancy episodes, outcomes, and mother-infant pairs in the Vaccine Safety Datalink.

^,

⁹⁸

Sejvar J.J.
Kohl K.S.
Gidudu J.
et al.

Brighton Collaboration GBS. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data.

^,

⁹⁹

Wang S.V.
Stefanini K.
Lewis E.
et al.

Determining which of several simultaneously administered vaccines increase risk of an adverse event.

The vaccine should demonstrate the potential to reduce morbidity in the pregnant woman and/or her fetus. In addition, there should exist a lack of evidence of adverse pregnancy outcomes or potential harm to the fetus or mother with vaccine exposure.

¹⁰⁰

Newcomer S.R.
Daley M.F.
Narwaney K.J.
et al.

Order of live and inactivated vaccines and risk of nonvaccine-targeted infections in US children 11-23 months of age.

^,

¹⁰¹

Glanz J.M.
Clarke C.L.
Xu S.
et al.

Association between rotavirus vaccination and type 1 diabetes in children.

^,

¹⁰²

Li R.
Stewart B.
Rose C.

A Bayesian approach to sequential analysis in post-licensure vaccine safety surveillance.

^,

¹⁰³

Yu W.
Zheng C.
Xie F.
et al.

The use of natural language processing to identify vaccine-related anaphylaxis at five health care systems in the Vaccine Safety Datalink.

^,

¹⁰⁴

Groom H.C.
Smith N.
Irving S.A.
et al.

Uptake and safety of hepatitis A vaccination during pregnancy: a Vaccine Safety Datalink study.

^,

¹⁰⁵

Myers T.R.
McCarthy N.L.
Panagiotakopoulos L.
Omer S.B.

Estimation of the incidence of Guillain-Barré syndrome during pregnancy in the United States.

^,

¹⁰⁶

Dudley M.Z.
Halsey N.A.
Omer S.B.
et al.

The state of vaccine safety science: systematic reviews of the evidence.

^,

¹⁰⁷

Kochhar S.

Communicating vaccine safety during the development and introduction of vaccines.

^,

¹⁰⁸

Fortner K.B.
Nieuwoudt C.
Reeder C.F.
Swamy G.K.

Infections in pregnancy and the role of vaccines.

^,

⁹⁶

McNeil M.M.
Gee J.
Weintraub E.S.
et al.

The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

^,

⁹⁷

Naleway A.L.
Gold R.
Kurosky S.
et al.

Identifying pregnancy episodes, outcomes, and mother-infant pairs in the Vaccine Safety Datalink.

^,

⁹⁸

Sejvar J.J.
Kohl K.S.
Gidudu J.
et al.

Brighton Collaboration GBS. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data.

^,

⁹⁹

Wang S.V.
Stefanini K.
Lewis E.
et al.

Determining which of several simultaneously administered vaccines increase risk of an adverse event.

Multiple randomized control trials and prospective studies have demonstrated vaccine efficacy against influenza-related morbidity in the pregnant patient and laboratory-confirmed infection in their neonates, with an additional 6 months of efficacy during early infancy.

⁸⁹

Sakala I.G.
Honda-Okubo Y.
Fung J.
Petrovsky N.

Influenza immunization during pregnancy: benefits for mother and infant.

^,

⁹⁰

Blanchard-Rohner G.
Meier S.
Bel M.
et al.

Influenza vaccination given at least 2 weeks before delivery to pregnant women facilitates transmission of seroprotective influenza-specific antibodies to the newborn.

^,

⁹¹

Chao A.S.
Chang Y.L.
Chao A.
et al.

Seropositivity of influenza A H1NI in mothers and infants following maternal vaccination with trivalent seasonal influenza vaccine after the 2009 pandemic.

^,

⁹²

Keller-Stanislawski B.
Englund J.A.
Kang G.
et al.

Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

^,

⁹³

Donahue J.G.
Kieke B.A.
King J.P.
et al.

Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012-13, 2013-14, and 2014-15.

^,

⁹⁴

Quach T.H.T.
Mallis N.A.
Cordero J.F.

Influenza vaccine efficacy and effectiveness in pregnant women: systematic review and meta-analysis.

^,

⁹⁵

Takeda S.
Hisano M.
Komano J.
Yamamoto H.
Sago H.
Yamaguchi K.

Influenza vaccination during pregnancy and its usefulness to mothers and their young infants.

In addition, these safety data included comprehensive studies and monitoring programs for the adjuvant- and nonadjuvant-containing inactivated trivalent seasonal influenza vaccine and the H1N1 monovalent vaccines.

⁸⁹

Sakala I.G.
Honda-Okubo Y.
Fung J.
Petrovsky N.

Influenza immunization during pregnancy: benefits for mother and infant.

^,

⁹⁰

Blanchard-Rohner G.
Meier S.
Bel M.
et al.

Influenza vaccination given at least 2 weeks before delivery to pregnant women facilitates transmission of seroprotective influenza-specific antibodies to the newborn.

^,

⁹¹

Chao A.S.
Chang Y.L.
Chao A.
et al.

Seropositivity of influenza A H1NI in mothers and infants following maternal vaccination with trivalent seasonal influenza vaccine after the 2009 pandemic.

^,

⁹²

Keller-Stanislawski B.
Englund J.A.
Kang G.
et al.

Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

^,

⁹³

Donahue J.G.
Kieke B.A.
King J.P.
et al.

Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012-13, 2013-14, and 2014-15.

^,

⁹⁴

Quach T.H.T.
Mallis N.A.
Cordero J.F.

Influenza vaccine efficacy and effectiveness in pregnant women: systematic review and meta-analysis.

^,

⁹⁵

Takeda S.
Hisano M.
Komano J.
Yamamoto H.
Sago H.
Yamaguchi K.

Influenza vaccination during pregnancy and its usefulness to mothers and their young infants.

With support from the CDC, American Academy of Pediatrics, American Academy of Family Medicine, ACIP, and ACOG, a consensus statement was published, recommending that all women receive both the seasonal and 2009 H1N1 inactivated vaccines during pregnancy with FDA approval within 6 months from the start of the H1N1 pandemic.

¹⁰⁹

U.S. Food and Drug Administration
Use of influenza A (H1N1) 2009 monovalent influenza vaccine in pregnant women.

Google Scholar

^,

¹¹⁰

Fiore A.E.
Uyeki T.M.
Broder K.
et al.

Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010.

^,

¹¹¹

Grohskopf L.A.
Alyanak E.
Broder K.R.
et al.

Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 influenza season.

^,

¹¹²

ACOG Committee Opinion no. 732: influenza vaccination during pregnancy.

These vaccines, along with known toxoids, have been used to prevent infectious morbidity known to negatively impact maternal and neonatal health.

¹⁰⁹

U.S. Food and Drug Administration
Use of influenza A (H1N1) 2009 monovalent influenza vaccine in pregnant women.

Google Scholar

^,

¹¹⁰

Fiore A.E.
Uyeki T.M.
Broder K.
et al.

Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010.

^,

¹¹¹

Grohskopf L.A.
Alyanak E.
Broder K.R.
et al.

Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 influenza season.

^,

¹¹²

ACOG Committee Opinion no. 732: influenza vaccination during pregnancy.

^,

¹¹³

Centers for Disease Control and Prevention (CDC)
Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012.

For example, the administration of the seasonal and H1N1 influenza vaccine and tetanus toxoid vaccine (combined with diphtheria-pertussis, Tdap) has resulted in a 92% reported reduction in global pertussis morbidity and mortality.

¹¹³

Centers for Disease Control and Prevention (CDC)
Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012.

With the disclosure of full intent to perform future research on COVID-19 vaccine safety in this population, the DHHS, companies, and researchers prioritized the emergent delivery of a safe and effective vaccine to the public, responding to an emergent call to action, unfortunately with limited time and lower thresholds for evidence before implementation for the pregnant and lactating patient.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

²²

Voysey M.
Clemens S.A.C.
Madhi S.A.
et al.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

^,

²³

Folegatti P.M.
Ewer K.J.
Aley P.K.
et al.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

^,

²⁴

LaCourse S.
John-Stewart G.
Adams Waldorf K.M.

Importance of inclusion of pregnant and breastfeeding women in COVID-19 therapeutic trials.

^,

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

Coronavirus Disease 2019 Vaccine and Pregnancy

Maternal risks and benefits

On December 19, 2020, the CDC and ACIP released a statement supporting the administration of both EUA-approved vaccines to prevent COVID-19 in persons aged ≥16 and 18 years, respectively, starting with prioritization groups outlined by the ACIP.

⁵⁰

Centers for Disease Control and Prevention
COVID-19 (coronavirus disease): people with certain medical conditions.

Google Scholar

^,

⁵²

Advisory Committee on Immunization Practices (ACIP). ACIP recommendations.

Google Scholar

^,

⁵³

Dooling K.
Marin M.
Wallace M.
et al.

The Advisory Committee on Immunization Practices’ updated interim recommendation for allocation of COVID-19 vaccine - United States, December 2020.

This strategy includes beginning with healthcare personnel and long-term care facility residents (Phase 1a), followed by persons aged ≥75 years and nonhealthcare frontline essential workers (Phase 1b), and in Phase 1c, the vaccines should be offered to persons aged 65 to 74 years, persons aged 16 to 64 years with high-risk medical conditions, and essential workers not included in Phase 1b.

⁵⁰

Centers for Disease Control and Prevention
COVID-19 (coronavirus disease): people with certain medical conditions.

Google Scholar

^,

⁵²

Advisory Committee on Immunization Practices (ACIP). ACIP recommendations.

Google Scholar

^,

⁵³

Dooling K.
Marin M.
Wallace M.
et al.

The Advisory Committee on Immunization Practices’ updated interim recommendation for allocation of COVID-19 vaccine - United States, December 2020.

In addition, the CDC, ACOG, SMFM, and other agencies support offering vaccination to pregnant and lactating women in these prioritized groups.

⁴⁷

The American College of Obstetricians and Gynecologists
Vaccinating pregnant and lactating patients against COVID-19.

Google Scholar

^,

⁴⁸

Society for Maternal-Fetal Medicine (SMFM) Statement: SARS-Co-V-2 Vaccination in pregnancy. Available at: https://s3.amazonaws.com/cdn.smfm.org/media/2591/SMFM_Vaccine_Statement_12-1-20. Accessed Jan. 19, 2021

Google Scholar

^,

⁴⁹

Academy of Breastfeeding Medicine
Considerations for COVID-19 vaccination in lactation. ABM Statement.

Google Scholar

^,

⁵⁰

Centers for Disease Control and Prevention
COVID-19 (coronavirus disease): people with certain medical conditions.

Google Scholar

^,

⁵¹

Royal College of Obstetricians and Gynaecologists
Updated advice on COVID-19 vaccination in pregnancy and women who are breastfeeding.

Google Scholar

^,

⁵²

Advisory Committee on Immunization Practices (ACIP). ACIP recommendations.

Google Scholar

^,

⁵³

Dooling K.
Marin M.
Wallace M.
et al.

The Advisory Committee on Immunization Practices’ updated interim recommendation for allocation of COVID-19 vaccine - United States, December 2020.

Counseling should include discussion of the risks and benefits for those contemplating vaccination before or during pregnancy or while breastfeeding with their trusted provider and support network. Mild side effects have been reported, ranging from a >80% frequency of pain at injection site to a 40% rate of systemic complaints, including febrile morbidity, which on review has been disproven to be teratogenic to the fetus during the first trimester of pregnancy.

¹¹⁴

Sass L.
Urhoj S.K.
Kjærgaard J.
Dreier J.W.
Strandberg-Larsen K.
Nybo Andersen A.M.

Fever in pregnancy and the risk of congenital malformations: a cohort study.

^,

¹¹⁵

Andersen A.M.
Vastrup P.
Wohlfahrt J.
Andersen P.K.
Olsen J.
Melbye M.

Fever in pregnancy and risk of fetal death: a cohort study.

Bell palsy affected few recipients of both Pfizer-BioNTech and Moderna vaccines but was not attributed to the vaccination.

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

Counseling regarding anticipated benefits is clear, as published data reveal between 94% and 95% efficacy in preventing laboratory-confirmed and mildly symptomatic COVID-19 among people 7 to 14 days after completion of the vaccine series, with potential for similar efficacy for the pregnant patient based on similar efficacy observed between pregnant and nonpregnant individuals in other vaccine trials, regardless of pregnancy specifics.

¹³

U.S. Food and Drug Administration
FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.

Google Scholar

^,

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

^,

⁸¹

Craig A.M.
AM
Hughes B.L.
Swamy G.K.

COVID-19 vaccines in pregnancy.

^,

⁹⁶

McNeil M.M.
Gee J.
Weintraub E.S.
et al.

The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

^,

¹⁰⁹

U.S. Food and Drug Administration
Use of influenza A (H1N1) 2009 monovalent influenza vaccine in pregnant women.

Google Scholar

Major secondary endpoints of the BioNTech and Moderna COVID-19 vaccine studies include the efficacy of the vaccine against severe infection-related morbidity, defined by the FDA as confirmed COVID-19 with clinical signs that are indicative of severe systemic illness, including respiratory failure, evidence of shock, significant acute organ dysfunction, admission to an ICU, or death.

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

Although preliminary data report lower hospitalizations among vaccine recipients, these valuable data are not yet available and therefore cannot be fully addressed when counseling the pregnant patient concerned about these more serious outcomes or the potential reduction in the long-term sequelae of COVID-19 or risk of continued transmissibility.

¹⁴

U.S. Food and Drug Administration
Pfizer COVID-19 vaccine emergency use authorization.

Google Scholar

^,

¹⁵

Polack F.P.
Thomas S.J.
Kitchin N.
et al.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.

^,

¹⁶

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine - United States, December 2020.

^,

¹⁷

U.S. Food and Drug Administration
Moderna COVID-19 vaccine.

Google Scholar

^,

¹⁸

Oliver S.E.
Gargano J.W.
Marin M.
et al.

The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine - United States, December 2020.

^,

¹⁹

Jackson L.A.
Anderson E.J.
Rouphael N.G.
et al.

An mRNA vaccine against SARS-CoV-2 - preliminary report.

^,

²⁰

Baden L.R.
El Sahly H.M.
Essink B.
et al.

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.

^,

²¹

Advisory Committee on Immunization Practices
ACIP recommendations.

Google Scholar

If validated, a reduction in severe COVID-19 would benefit the fetus, given the negative effects maternal illness has on fetal status, which has driven medically indicated and spontaneous preterm birth and associated neonatal sequelae.

²⁸

Huntley B.J.F.
Huntley E.S.
Di Mascio D.
Chen T.
Berghella V.
Chauhan S.P.

Rates of maternal and perinatal mortality and vertical transmission in pregnancies complicated by severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) infection: a systematic review.

^,

²⁹

Adhikari E.H.
Moreno W.
Zofkie A.C.
et al.

Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection.

^,

³⁰

Handley S.C.
Mullin A.M.
Elovitz M.A.
et al.

Changes in preterm birth phenotypes and stillbirth at 2 Philadelphia hospitals during the SARS-CoV-2 pandemic, March-June 2020.

^,

³¹

Pineles B.L.
Alamo I.C.
Farooq N.
et al.

Racial-ethnic disparities and pregnancy outcomes in SARS-CoV-2 infection in a universally-tested cohort in Houston, Texas.

^,

³²

Ahlberg M.
Neovius M.
Saltvedt S.
et al.

Association of SARS-CoV-2 test status and pregnancy outcomes.

^,

³³

Pettirosso E.
Giles M.
Cole S.
Rees M.

COVID-19 and pregnancy: a review of clinical characteristics, obstetric outcomes and vertical transmission.

^,

³⁴

Di Mascio D.
Khalil A.
Saccone G.
et al.

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.

^,

³⁵

DeBolt C.A.
Bianco A.
Limaye M.A.
et al.

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

^,

³⁶

Hantoushzadeh S.
Shamshirsaz A.A.
Aleyasin A.
et al.

Maternal death due to COVID-19.

^,

³⁷

Pierce-Williams R.A.M.
Burd J.
Felder L.
et al.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

^,

³⁸

Juan J.
Gil M.M.
Rong Z.
Zhang Y.
Yang H.
Poon L.C.

Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.

^,

³⁹

Dashraath P.
Wong J.L.J.
Lim M.X.K.
et al.

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

^,

⁴⁰

Knight M.
Bunch K.
Vousden N.
et al.

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

^,

⁴¹

Moore J.T.
Ricaldi J.N.
Rose C.E.
et al.

Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 states, February-June 2020.

^,

⁴²

Panagiotakopoulos L.
Myers T.R.
Gee J.
et al.

SARS-CoV-2 infection among hospitalized pregnant women: reasons for admission and pregnancy characteristics - eight U.S. health care centers, March 1-May 30, 2020.

^,

⁴³

Delahoy M.J.
Whitaker M.
O’Halloran A.
et al.

Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 - COVID-NET, 13 states, March 1-August 22, 2020.

^,

⁴⁴

Ellington S.
Strid P.
Tong V.T.
et al.

Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020.

^,

⁴⁵

Zambrano L.D.
Ellington S.
Strid P.
et al.

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.

^,

⁴⁶

Jering K.S.
Claggett B.L.
Cunningham J.W.
et al.

Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19.

Counseling to this point can include a discussion of the continued pursuit and accumulation of pregnancy-specific COVID-19 data worldwide, with current data suggesting that rates of severe morbidity (assisted ventilation, ICU admission, and death) are significantly higher among pregnant women with symptomatic COVID-19 compared with symptomatic nonpregnant cohorts, respectively, which equally affect 5% of persons with infection.

³⁵

DeBolt C.A.
Bianco A.
Limaye M.A.
et al.

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

^,

³⁶

Hantoushzadeh S.
Shamshirsaz A.A.
Aleyasin A.
et al.

Maternal death due to COVID-19.

^,

³⁷

Pierce-Williams R.A.M.
Burd J.
Felder L.
et al.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

^,

³⁸

Juan J.
Gil M.M.
Rong Z.
Zhang Y.
Yang H.
Poon L.C.

Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.

^,

³⁹

Dashraath P.
Wong J.L.J.
Lim M.X.K.
et al.

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

^,

⁴⁰

Knight M.
Bunch K.
Vousden N.
et al.

Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study.

^,

⁴¹

Moore J.T.
Ricaldi J.N.
Rose C.E.
et al.

Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 states, February-June 2020.

^,

⁴²

Panagiotakopoulos L.
Myers T.R.
Gee J.
et al.

SARS-CoV-2 infection among hospitalized pregnant women: reasons for admission and pregnancy characteristics - eight U.S. health care centers, March 1-May 30, 2020.

^,

⁴³

Delahoy M.J.
Whitaker M.
O’Halloran A.
et al.

Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 - COVID-NET, 13 states, March 1-August 22, 2020.

^,

⁴⁴

Ellington S.
Strid P.
Tong V.T.
et al.

Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020.

^,

⁴⁵

Zambrano L.D.
Ellington S.
Strid P.
et al.

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.

^,

⁴⁶

Jering K.S.
Claggett B.L.
Cunningham J.W.
et al.

Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19.

However, when examining critical care details and demographic variables of pregnant women with infection in large national epidemiologic data, it remains critical to acknowledge that in the largest studies to date, the rates of ICU admission, invasive ventilation, and mortality from COVID-19 are 2- to 3-fold higher among symptomatic pregnant women over 35 years of age, with comorbidities (obesity, diabetes, cardiovascular disease, chronic lung disease), Black or Asian race or Hispanic ethnicity (Table 2).

³⁵

DeBolt C.A.
Bianco A.
Limaye M.A.
et al.

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

^,

³⁶

Hantoushzadeh S.
Shamshirsaz A.A.
Aleyasin A.
et al.

Maternal death due to COVID-19.

^,

³⁷

Pierce-Williams R.A.M.
Burd J.
Felder L.
et al.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

^,

³⁸

Juan J.
Gil M.M.
Rong Z.
Zhang Y.
Yang H.
Poon L.C.

Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.

^,

³⁹

Dashraath P.
Wong J.L.J.
Lim M.X.K.
et al.

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

Ab

Property	Value
Status
Version
Ad File
Disable Ads Flag
Environment
Moat Init
Moat Ready
Contextual Ready
Contextual URL
Contextual Initial Segments
Contextual Used Segments
AdUnit
SubAdUnit
Custom Targeting
Ad Events
Invalid Ad Sizes