The team at the CITF Secretariat has scoured numerous journals from around the world looking for answers about COVID, vaccines, and pregnancy. Here is what we’ve found:

People with COVID-19 who are pregnant are:

  • 65 times more likely to require hospitalization and
  • 46 times more likely to be admitted to ICU

than non-pregnant individuals with COVID-19.

Furthermore, COVID-19 infection has been associated with adverse pregnancy outcomes:

  • The rate of preterm birth was 11.1% among those who had COVID-19 while pregnant, compared to only 6.8% of those who did not have the disease while pregnant;
  • People with a laboratory-confirmed SARS-CoV-2 infection at the time they gave birth were more than twice as likely as uninfected people to have their baby be born prematurely or to die at birth.

Extensive research, including by CITF-affiliated researchers, has shown:

  • COVID-19 vaccines are safe for pregnant people and their babies;
  • Maternal vaccination offers benefits to the fetus, given that maternal antibodies are detected in the fetus within 16 days of vaccination;
  • Infants born with maternal antibodies against COVID-19 could be protected in the first several months of their lives, when they are most vulnerable;
  • At 6 months, 57% of infants born to mothers vaccinated with an mRNA vaccine had detectable antibodies compared with only 8% of infants born to unvaccinated mothers infected with COVID-19.

Antibodies can be transferred from mother to baby via the placenta and umbilical cord in utero, and through breast milk following birth. Research indicates that a mother being vaccinated in the late second or early third trimester may be optimal for high levels of anti-SARS-CoV-2 antibodies to be transferred to the baby before birth. Understanding the transfer of maternal antibodies to infants is important because maternal COVID-19 infections may account for a disproportionate burden of pediatric SARS-CoV-2–associated morbidity and vaccines are not currently available for infants younger than 6 months.

Details below.

Pregnant people and their newborns are at increased risk of adverse events due to COVID-19

Pregnant people are at an increased risk of adverse effects from SARS-CoV-2 infection (the infection that causes COVID-19 disease) and are more likely to be admitted to an intensive care unit compared to non-pregnant individuals (1-4). Overall, people with COVID-19 who are pregnant are 2.65 times more likely to require hospitalization and 5.46 times more likely to be admitted to ICU than non-pregnant individuals with COVID-19 (4). COVID-19 has also been associated with increased risks of preeclampsia, preterm birth, and other adverse pregnancy outcomes (5). Thus, vaccination is an important tool for ensuring a healthy pregnancy.

Extensive research, including by CITF-affiliated scientists, has shown COVID-19 vaccines to be safe for pregnant people and their babies (6-11). Maternal vaccination also offers benefits to the fetus and the infant, a subject discussed below.

Increased risk of adverse events when the mother contracts SARS-CoV-2

A study from CANCOVIDPreg in Canada showed that SARS-CoV-2 infection during pregnancy was significantly associated with increased risk of adverse maternal outcomes and preterm births (4). The rate of preterm birth was 11.1% among COVID-19-affected pregnancies, compared to only 6.8% among those that were unaffected. This elevated risk was observed even for mild cases of COVID-19 (4). Similarly, in the UK, researchers found that prior to the widespread availability of vaccines, people with a laboratory-confirmed SARS-CoV-2 infection at the time they gave birth were more than twice as likely as those who were uninfected to have their baby die at birth or be born prematurely (12).

In a CITF-funded study from the Canadian National Vaccine Safety (CANVAS) Network (13), Drs. Julie Bettinger and Manish Sadarangani looked at health events requiring time off work or school or needing medical attention in vaccinated and unvaccinated pregnant people compared to vaccinated non-pregnant people. There was no significant association between vaccination status and health issues in those who were pregnant. They also highlighted that pregnant participants had fewer significant adverse events after vaccination than did similarly aged non-pregnant participants.

In a CITF-funded population-based cohort study in Ontario, researchers explored COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination. Vaccination was not significantly associated with increased risk of adverse peripartum outcomes (14).

Vaccination prior to and during pregnancy provides protective immunity to the fetus

Research has found that mRNA–based vaccines in pregnant people cause maternal antibody production as early as five days after the first dose. Transplacental transfer to the fetus was detected as early as 16 days after the first vaccination dose (15, 16).  The increasing levels of maternal IgG and the transplacental transfer rate indicate that the timing between vaccination and birth may be an important factor to consider in vaccination strategies of pregnant people (15, 16).

A vaccine booster during the third trimester of pregnancy is also associated with strong maternal and neonatal humoral responses, as reflected by maternal and neonatal SARS-CoV-2 IgG antibody levels measured at birth (15). Overall, these findings support the administration of COVID-19 boosters to pregnant people to restore maternal and neonatal protective antibodies, given that they wane over time.

Maternal antibodies due to vaccination are transferred to the baby, offering the infant protection after birth

In addition to maternal protection against COVID-19, the mother’s vaccines provide various types of immunity to newborns, transferred via the placenta, umbilical cord, and breast milk. As Trostle emphasized in her 2021 article (16), if babies are born with antibodies against COVID-19, they could be protected in the first several months of their lives when they are most vulnerable.

A Morbidity and Mortality Weekly Report from February 2022 suggested completion of a two-dose mRNA series during pregnancy might help prevent COVID-19 hospitalization among infants aged <6 months (17).

Both spike- and RBD-specific IgG were detectable after maternal vaccination (18). Robust and comparable IgG titers were observed among vaccinated pregnant, lactating, and nonpregnant controls, all of which were significantly higher than those observed in pregnant people with previous SARS-CoV-2 infection. In their 2022 study published in JAMA, Shook and colleagues found that the majority of infants born to COVID-vaccinated mothers had persistent anti-S antibodies at six months compared with infants born to mothers who’d had a SARS-CoV-2 infection (19).

The findings below support the use of SARS-CoV-2 vaccines in pregnant people to protect both the mother and the child.

Immunity via the placenta and umbilical cord

Recent research suggests that maternal immunization provides neonatal protection through the transplacental transfer of antibodies (20). The newborn’s protection from infection is primarily dependent on neonatal innate immune responses and/or antibodies acquired via the mother’s placenta (21, 22). It is well established that IgG antibodies are actively transported to the fetus in the third trimester of pregnancy. A receptor on the placenta called Fcn is upregulated in the third trimester, thereby enabling antibodies present in the mother to be efficiently transferred to the fetus.

Among pregnant people vaccinated with Pfizer (BNT162b2), there was a demonstrated transfer of SARS-CoV-2 IgG across the placenta from the mother to their fetus with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity (22). At six months, 57% of infants born to mothers vaccinated with an mRNA vaccine had detectable antibodies compared with 8% of infants born to mothers with a COVID-19 infection (19).

Two doses of vaccine given to the mother resulted in significantly greater antibody persistence in infants than did a COVID infection in an unvaccinated mother (19). Two maternal SARS-CoV-2 vaccine doses during pregnancy led to significantly higher maternal and cord anti-SARS-CoV-2 IgG levels compared to one dose (18, 19, 23, 24). Antibody concentrations appear to be at least as high in infant cord blood as in the maternal circulation, and at least two vaccine doses during pregnancy are likely needed to reach maximal concentrations (25).

Emerging data demonstrate the presence of anti-SARS-CoV-2 IgG in umbilical cord blood following maternal vaccination with mRNA vaccines, with antibody transfer ratios (i.e. the ratio of maternal antibody to cord blood antibody) showing a strong correlation with both maternal antibody levels, time elapsed since vaccination, and whether one or both doses had been received (18, 24, 26, 27).

A booster shot was associated with augmented IgG levels in the blood, translating to the increased transfer of IgG to the fetus through the placenta (9).

Immunity via breast milk

Data suggest that maternal SARS-CoV-2-specific binding antibodies are efficiently transferred via breast milk following maternal mRNA vaccination, much like through the placenta (15, 17). Unlike in the placenta, however, where the antibody concentrations appear to be at least as high in infant cord blood as in the maternal serum, antibody concentrations are lower in breast milk (18).

Breast milk IgA rises rapidly following maternal vaccination, whereas IgG rises later, but may persist longer. Moreover, these antibodies retain a strong neutralizing capacity. At least two doses of vaccine appear to be required to reach maximal antibody concentrations in breast milk, as is the case for the cord blood (25). A booster shot was also associated with augmented IgG levels in the blood, translating to the increased transfer of IgG to the neonate through breast milk (9).

For protecting newborns, antibodies are efficiently transferred through breast milk, suggesting a potential prevention of infection in these newborns with undeveloped immune systems. There is clear evidence of SARS-CoV-2 specific IgA and IgG antibodies in breast milk for six weeks after vaccination. IgA secretion was evident as early as two weeks after vaccination, followed by a spike in IgG after four weeks (one week after the second vaccine). Antibodies found in breast milk showed strong neutralizing effects, suggesting a potential protective effect against infection in the infant (9, 15, 18, 25, 28-30).

Timing of maternal vaccination to give the baby the greatest immunity

Rottenstreich et al showed that vaccination of pregnant people early in the third trimester may enhance neonatal seroprotection (27). Because the transfer of maternal antibodies is most efficient in the third trimester, and it takes about three weeks for antibodies to peak after maternal vaccination, maternal SARS-CoV-2 immunization early in the third-trimester can enhance transplacental antibody transfer and increase neonatal neutralizing antibody levels (27).

Additionally, a study from Kugelman et al showed receipt of the Pfizer vaccine during the second trimester of pregnancy was also associated with maternal and neonatal humoral responses (31). Therefore, vaccination in the late second or early third trimester can lead to high levels of anti-SARS-CoV-2 antibodies being transferred to the baby before birth.

Further research on understanding the transfer of maternal antibodies to infants is important because COVID-19 infections may account for a disproportionate burden of pediatric SARS-CoV-2–associated morbidity and vaccines are not currently available for infants younger than 6 months (19).

References

  1. Lokken EM, Taylor GG, Huebner EM, Vanderhoeven J, Hendrickson S, Coler B, et al. Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients. American Journal of Obstetrics & Gynecology. 2021;225(1):75.e1-.e16.
  2. Cassaniti I, Percivalle E, Zelini P, Ngaradoumbe Nanhorngue K, Parolo A, Bernardi V, et al. Both SARS-CoV-2 infection and vaccination in pregnancy elicited neutralizing antibodies in pregnant women and newborns. Clinical Microbiology and Infection. 2021;27(11):1708-9.
  3. Pirjani R, Hosseini R, Soori T, Rabiei M, Hosseini L, Abiri A, et al. Maternal and neonatal outcomes in COVID-19 infected pregnancies: a prospective cohort study. Journal of Travel Medicine. 2020;27(7).
  4. McClymont E, Albert AY, Alton GD, Boucoiran I, Castillo E, Fell DB, et al. Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes. Jama. 2022;327(20):1983-91.
  5. Wei SQ, Bilodeau-Bertrand M, Liu S, Auger N. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. Cmaj. 2021;193(16):E540-e8.
  6. De Rose DU, Salvatori G, Dotta A, Auriti C. SARS-CoV-2 Vaccines during Pregnancy and Breastfeeding: A Systematic Review of Maternal and Neonatal Outcomes. Viruses. 2022;14(3).
  7. Olson CK. COVID-19 vaccine safety in pregnancy: updates from the v-safe COVID-19 Vaccine Pregnancy Registry. 2021.
  8. Magnus MC, Gjessing HK, Eide HN, Wilcox AJ, Fell DB, Håberg SE. Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage. N Engl J Med. 2021;385(21):2008-10.
  9. Principi N, Esposito S. Is the Immunization of Pregnant Women against COVID-19 Justified? Vaccines. 2021;9(9):970.
  10. Zauche LH, Wallace B, Smoots AN, Olson CK, Oduyebo T, Kim SY, et al. Receipt of mRNA COVID-19 vaccines preconception and during pregnancy and risk of self-reported spontaneous abortions, CDC v-safe COVID-19 Vaccine Pregnancy Registry 2020-21. Res Sq. 2021.
  11. Fu W, Sivajohan B, McClymont E, Albert A, Elwood C, Ogilvie G, et al. Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants. Int J Gynaecol Obstet. 2022;156(3):406-17.
  12. Gurol-Urganci I, Jardine JE, Carroll F, Draycott T, Dunn G, Fremeaux A, et al. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection at the time of birth in England: national cohort study. American Journal of Obstetrics & Gynecology. 2021;225(5):522.e1-.e11.
  13. Sadarangani M, Soe P, Shulha H, Valiquette L, Vanderkooi OG, Kellner JD, et al. Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) Network study. medRxiv. 2022:2022.02.22.22271358 (Lancet Infectious Diseases, in press)
  14. Fell DB, Dhinsa T, Alton GD, Török E, Dimanlig-Cruz S, Regan AK, et al. Association of COVID-19 Vaccination in Pregnancy With Adverse Peripartum Outcomes. Jama. 2022;327(15):1478-87.
  15. Collier AY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. Jama. 2021;325(23):2370-80.
  16. Trostle ME, Aguero-Rosenfeld ME, Roman AS, Lighter JL. High antibody levels in cord blood from pregnant women vaccinated against COVID-19. American Journal of Obstetrics & Gynecology MFM. 2021;3(6).
  17. Halasa NB, Olson SM, Staat MA, Newhams MM, Price AM, Boom JA, 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.
  18. Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. American Journal of Obstetrics and Gynecology. 2021;225(3):303.e1-.e17.
  19. Shook LL, Atyeo CG, Yonker LM, Fasano A, Gray KJ, Alter G, et al. Durability of Anti-Spike Antibodies in Infants After Maternal COVID-19 Vaccination or Natural Infection. JAMA. 2022;327(11):1087-9.
  20. Zdanowski W, Waśniewski T. Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results. Vaccines. 2021;9(6):675.
  21. Flannery DD, Gouma S, Dhudasia MB, Mukhopadhyay S, Pfeifer MR, Woodford EC, et al. Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios. JAMA Pediatrics. 2021;175(6):594-600.
  22. Nir O, Schwartz A, Toussia-Cohen S, Leibovitch L, Strauss T, Asraf K, et al. Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy. Am J Obstet Gynecol MFM. 2022;4(1):100492.
  23. Beharier O, Mayo RP, Raz T, Sacks KN, Schreiber L, Suissa-Cohen Y, et al. Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. The Journal of clinical investigation. 2021;131(13).
  24. Mithal LB, Otero S, Shanes ED, Goldstein JA, Miller ES. Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy. Am J Obstet Gynecol. 2021;225(2):192-4.
  25. Jorgensen SCJ, Burry L, Tabbara N. Role of maternal COVID-19 vaccination in providing immunological protection to the newborn. Pharmacotherapy. 2022;42(1):58-70.
  26. Prabhu M, Murphy EA, Sukhu AC, Yee J, Singh S, Eng D, et al. Antibody Response to Coronavirus Disease 2019 (COVID-19) Messenger RNA Vaccination in Pregnant Women and Transplacental Passage Into Cord Blood. Obstetrics & Gynecology. 2021;138(2).
  27. Rottenstreich A, Zarbiv G, Oiknine-Djian E, Vorontsov O, Zigron R, Kleinstern G, et al. Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study. Clin Microbiol Infect. 2022;28(3):419-25.
  28. Perl SH, Uzan-Yulzari A, Klainer H, Asiskovich L, Youngster M, Rinott E, et al. SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. JAMA. 2021;325(19):2013-4.
  29. Pace RM, Williams JE, Järvinen KM, Belfort MB, Pace CDW, Lackey KA, et al. Characterization of SARS-CoV-2 RNA, Antibodies, and Neutralizing Capacity in Milk Produced by Women with COVID-19. mBio. 2021;12(1).
  30. Romero Ramírez DS, Lara Pérez MM, Carretero Pérez M, Suárez Hernández MI, Martín Pulido S, Pera Villacampa L, et al. SARS-CoV-2 Antibodies in Breast Milk After Vaccination. Pediatrics. 2021;148(5).
  31. Kugelman N, Nahshon C, Shaked-Mishan P, Cohen N, Sher ML, Gruber M, et al. Maternal and Neonatal SARS-CoV-2 Immunoglobulin G Antibody Levels at Delivery After Receipt of the BNT162b2 Messenger RNA COVID-19 Vaccine During the Second Trimester of Pregnancy. JAMA Pediatr. 2022;176(3):290-5.