Is COVID-19 Vaccination in Pregnancy Safe? Is It Protective?

I thought it would be helpful to do a roundup of studies investigating the safety and protective effects of COVID-19 vaccination in pregnant women. These are studies I have been accumulating for the past couple of years either because I get study publication notices from the journals that report on obstetric research or because my Google alerts picked them up.

I’ve been collecting studies that fall into three categories:

1. studies looking at whether vaccination in pregnancy harmed the fetus,
2. studies determining the risks to mothers and babies resulting from COVID-19 maternal infection, and
3. studies evaluating the protective effect of maternal vaccination.

Let’s see what they found.  

#1 Is COVID-19 vaccination safe?

The question here is whether vaccination in pregnancy increases the risk of adverse newborn outcomes above background rates because, of course, a certain percentage of pregnancies end in adverse outcomes unrelated to COVID-19 infection. In answer to that question, studies have found that COVID-19 vaccination in pregnancy doesn’t increase the occurrence of:

• Fetal anomalies^{6, 12, 15, 17}
• Miscarriage^{9, 17, 21}
• Preterm birth (birth before 37 weeks gestation)^{6, 10, 17}
• Small-for-gestational-age (birthweight in the lowest 10% for gestational age)^{6, 10, 17}
• Hospitalization initiated between 1 day and 28 days after birth⁶
• Deaths within 180 days of birth⁶

Conclusion: Research has unequivocally shown that COVID-19 vaccination in pregnancy is safe.

#2 Does COVID-19 infection increase adverse outcomes in pregnant women and babies compared with uninfected pregnant women?

On the one hand, this question is kind of a no-brainer because no one doubts that the COVID-19 virus is capable of causing severe illness. Still, understanding what serious harms maternal infection causes in mothers and babies and whether their occurrence significantly exceeds adverse outcome rates in uninfected pregnant women is important information.

Beginning with mothers, infected women are more likely to experience:

• Admission to intensive care^{1, 12, 19}
• Respiratory intubation and mechanical ventilation¹
• Severe maternal morbidity (at least one complication on a list of severe and life-threatening complications)^{5, 12}
• Venous thromboembolism (deep venous blood clots)⁵
• Death^{1, 12, 19}

Of note, one study found that pregnant women were at higher risk of experiencing severe COVID-19 illness compared with infected women in the same age range who weren’t pregnant.¹¹ In other words, pregnancy was a risk factor for severe COVID-19 illness.

Turning to babies, the babies of infected women are more likely to experience:

• Preterm birth (birth before 37 weeks gestation)^{1, 5, 11, 12, 19}
• Admission to neonatal intensive care¹⁴
• Severe neonatal or perinatal morbidity (at least one complication on a list of severe and life-threatening complications)^{12, 19}
• Respiratory distress syndrome and other respiratory disorders¹⁴
• Death^{3, 12, 18} (A fourth study found a trend toward increased mortality, but the number of participants was too small to be confident that the difference was unlikely to be due to chance.¹⁴)

Severe complications in babies were mostly due not to perinatal infection, but to preterm delivery as a result of their mother’s illness.¹⁴

Conclusion: Research has unequivocally shown that failure to vaccinate poses serious threats to the health of mothers and babies.

#3 Does vaccination in pregnancy protect against COVID-19 infection and against severe adverse outcomes consequent to COVID-19 infection?

This question is a two-parter: Part 1 is whether COVID-19 vaccination prevents COVID-19 infection in mothers and babies, and Part 2 is whether it protects against severe adverse outcomes when breakthrough infections occur in vaccinated women. In answer to Part 1, COVID-19 vaccination in pregnancy:

• Prevents maternal infection^{16, 18}
• Passively immunizes babies by passing vaccine-induced maternal antibodies to the baby via the placenta⁷
• Passively immunizes breastfed babies by passing vaccine-induced maternal antibodies via breastmilk^{4, 7, 13, 20}

In answer to Part 2, vaccination in pregnancy:

Protects women against developing severe illness with breakthrough infections^{16, 18}

Protects babies against hospital admission for severe illness⁸

Conclusion: Research has unequivocally shown that vaccination in pregnancy protects pregnant women against infection and against severe illness when breakthrough infections occur. It also enables women to protect their babies by passing COVID-19 antibodies to them during pregnancy and after birth via breastmilk.

The Take-Away

For the take-away, I can’t do better than to quote the conclusions of some of the researchers:

Evidence of the benefits of COVID-19 vaccination during pregnancy continues to accrue . . . . Together, these findings reinforce the importance of communicating the risks for COVID-19 during pregnancy, the benefits of vaccination, and information on the safety and effectiveness of COVID-10 vaccination during pregnancy.

—Lipkind (2022)¹⁰

These findings underscore the importance of COVID-19 prevention strategies, including vaccination before or during pregnancy.

—DeSisto (2021)³

Our analysis indicates . . . that vaccination appears to be the safest and most effective way for pregnant women both to protect themselves and their babies from the complications of a [COVID-19] infection.

—Aziz Sheikh, co-author Stock (2022)²

References

Note: All of these studies are available for free.

1. Chinn J, Sedighim S, Kirby KA, et al. Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic. JAMA Netw Open 2021;4(8):e2120456.

2. COVID Vaccination in Pregnant Women Protective for Infants. Medpage Today, 2022. (Accessed Jan 25, 2022, 2022, at https://www.medpagetoday.com/obgyn/pregnancy/96661#:~:text=%22Our%20analysis%20indicates%20…,study%2C%20in%20a%20press%20briefing.)

3. DeSisto CL, Wallace B, Simeone RM, et al. Risk for Stillbirth Among Women With and Without COVID-19 at Delivery Hospitalization – United States, March 2020-September 2021. MMWR Morb Mortal Wkly Rep 2021;70(47):1640-5.

4. Esteve-Palau E, Gonzalez-Cuevas A, Guerrero ME, et al. Quantification of Specific Antibodies Against SARS-CoV-2 in Breast Milk of Lactating Women Vaccinated With an mRNA Vaccine. JAMA Netw Open 2021;4(8):e2120575.

5. Ferrara A, Hedderson MM, Zhu Y, et al. Perinatal Complications in Individuals in California With or Without SARS-CoV-2 Infection During Pregnancy. JAMA Intern Med 2022;182(5):503-12.

6. Goldshtein I, Steinberg DM, Kuint J, et al. Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes. JAMA Pediatr 2022;176(5):470-7.

7. Gray KJ, Bordt EA, Atyeo C, et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol 2021;225(3):303 e1- e17.

8. Halasa NB, Olson SM, Staat MA, et al. Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19-Associated Hospitalization in Infants Aged <6 Months – 17 States, July 2021-January 2022. MMWR Morb Mortal Wkly Rep 2022;71(7):264-70.

9. Kharbanda EO, Haapala J, DeSilva M, et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA 2021;326(16):1629-31.

10. Lipkind HS, Vazquez-Benitez G, DeSilva M, et al. Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth – Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021. MMWR Morb Mortal Wkly Rep 2022;71(1):26-30.

11. McClymont E, Albert AY, Alton GD, et al. Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes. JAMA 2022;327(20):1983-91.

12. Metz TD, Clifton RG, Hughes BL, et al. Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications. JAMA 2022;327(8):748-59.

13. Narayanaswamy V, Pentecost BT, Schoen CN, et al. Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination. Obstet Gynecol 2022;139(2):181-91.

14. Norman M, Naver L, Soderling J, et al. Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes. JAMA 2021;325(20):2076-86.

15. Ruderman RS, Mormol J, Trawick E, et al. Association of COVID-19 Vaccination During Early Pregnancy With Risk of Congenital Fetal Anomalies. JAMA Pediatr 2022.

16. Seasely AR, Blanchard CT, Arora N, et al. Maternal and Perinatal Outcomes Associated With the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) Variant. Obstet Gynecol 2021;138(6):842-4.

17. Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med 2021;384(24):2273-82.

18. Stock SJ, Carruthers J, Calvert C, et al. SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland. Nat Med 2022;28(3):504-12.

19. Villar J, Ariff S, Gunier RB, et al. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr 2021;175(8):817-26.

20. Young BE, Seppo AE, Diaz N, et al. Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination. JAMA Pediatr 2022;176(2):159-68.

21. Zauche LH, Wallace B, Smoots AN, et al. Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion. N Engl J Med 2021;385(16):1533-5.