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COVID-19 mRNA Vaccination of Pregnant and Lactating Women Generates Robust Maternal Immunity, May Provide Protection for Newborns

Key findings

  • This study evaluated antibody levels in blood/breastmilk/cord blood samples from 84 pregnant women, 31 lactating women and 16 nonpregnant women of reproductive age who received the Pfizer/BioNTech or Moderna COVID-19 vaccine
  • Antibody levels achieved after vaccination were significantly higher than those seen in pregnant women after natural infection with SARS-CoV-2
  • In both pregnant and lactating women, levels of IgG, IgA and IgM against SARS-CoV-2 rose after the first vaccine dose, and IgG levels rose further after the second dose. The final titers achieved by pregnant and lactating women were similar to those achieved by non-pregnant women of reproductive age
  • Vaccine-induced IgG was transferred across the placenta to the fetus in all 10 births that occurred during the study period, and vaccine-induced IgA and IgG were also present in breastmilk
  • Side effect scores did not differ between the three groups. Higher side effect scores after the second vaccine dose correlated with higher spike and RBD IgG antibody levels in serum and IgA and IgG antibody levels in breastmilk

Pregnant and lactating women were not included in the initial trials of the COVID-19 vaccines now authorized in the U.S. This is a particular concern because the first two vaccines that were authorized represent a completely novel vaccine platform: they make use of mRNA to deliver the SARS-CoV-2 spike antigen to educate the immune system.

Fortunately, Andrea G. Edlow, MD, MSc, an investigator in the Vincent Center for Reproductive Biology within the Department of Obstetrics and Gynecology at Massachusetts General Hospital, Galit Alter, PhD, principal investigator at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Kathryn Gray, MD, PhD, of Brigham and Women's Hospital, and colleagues have determined in a large cohort that immunogenicity and reactogenicity to the COVID-19 mRNA vaccines are similar to that observed in non-pregnant women, and antibodies are transferred to neonates via the placenta and breastmilk. Their report appears in the American Journal of Obstetrics and Gynecology.

Study Methods

Between December 17, 2020, and February 23, 2021, the researchers obtained blood/breastmilk samples from 84 pregnant women, 31 lactating women and 16 nonpregnant women of reproductive age who received either the Pfizer/BioNTech or Moderna vaccine.

Samples were collected at the time of the first vaccine dose, the time of the second dose, two to six weeks after the second dose and at delivery, if applicable. 13 women delivered during the study, and cord blood was collected at delivery from 10 of them. The researchers also analyzed banked sera from 37 pregnant women who developed COVID-19 between March 24 and December 11, 2020, and were not vaccinated.

Side Effects

Participants completed a questionnaire about their side effects, and a cumulative score was generated by assigning one point to each side effect. After the second dose, there was no significant difference between groups in the cumulative score, and scores were low (median 2–3). Up to 32% of pregnant women and 50% of nonpregnant women reported fevers/chills after the second dose.

Maternal Vaccine Response

The researchers measured IgG, IgA and IgM antibody responses to the spike protein (S), receptor-binding domain (RBD), and S1 and S2 segments. In both pregnant and lactating women, levels of antibodies to all antigens rose after the first vaccine dose, and IgG levels rose further after the second dose. In contrast, IgM and IgA were poorly induced after the second dose in all three groups.

Antibody levels were strikingly higher in vaccinated women (P<0.001) than in the 37 pregnant women who developed COVID-19. This highlights the strength of the immune responses induced by mRNA vaccination compared with "natural immunity."

Antibody Transfer via Breastmilk

  • Robust levels of IgG, IgA and IgM were present in breastmilk after the first vaccine dose
  • As in serum, IgA and IgM levels did not increase substantially after the second dose but IgG did
  • The higher the side effect score after the second dose, the higher the antibody levels in both serum and breastmilk

Antibody Transfer via the Placenta

  • S- and RBD-specific IgG were detectable in all 10 samples of cord blood
  • The longer the time between vaccination and delivery, the greater the transfer of S-specific IgG into the cord
  • Neutralizing antibodies were present in all but two cords

Counseling Patients

When engaging in shared decision-making about vaccination in pregnancy, patients and clinicians must consider maternal and fetal benefit, maternal and fetal harm, and effects on pregnancy outcomes. Maternal, neonatal and obstetric risks of COVID-19 during pregnancy are well documented and should be weighed carefully.

This study provides compelling evidence that the humoral immunity stimulated by COVID-19 mRNA vaccines is the same in pregnant and lactating women as in the non-pregnant population. However, there was no attempt to study potential risks to the fetus.

The Centers for Disease Control and Prevention is tracking the safety of COVID-19 vaccines using the V-Safe smartphone application. To date, as in this study, the results indicate no significant differences in side effects in pregnant versus non-pregnant women.

Learn more about the Vincent Center for Reproductive Biology

Refer a patient to the Department of Obstetrics & Gynecology

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Based on data from a prospective cohort study, Andrea G. Edlow, MD, MSc, and colleagues caution that transplacental transfer of anti–SARS-CoV-2 antibodies is inefficient, which may leave neonates at risk of infection.