By Rebecca H. Allen, MD, MPH
Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI
SYNOPSIS: In this case control study, 537 case infants younger than 6 months of age who were admitted to the hospital with COVID-19 were compared to 512 control infants who were hospitalized for other reasons; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against COVID-19 during the pregnancy. The effectiveness of maternal vaccination against infant hospitalization for COVID-19 was 52% overall, 80% during the Delta variant period, and 38% during the Omicron variant period. Effectiveness increased when the vaccine was received after 20 weeks of pregnancy.
SOURCE: Halasa NB, Olson SM, Staat MA, et al. Maternal vaccination and risk of hospitalization for Covid-19 among infants. N Engl J Med 2022;387:109-119.
Infants younger than 6 months of age are not eligible for the COVID-19 vaccine. COVID-19 vaccination in pregnancy produces maternal antibodies that transfer to the fetus when vaccination occurs late in the second trimester or early in the third trimester.1 This is the reason why the Tdap vaccine is given in the third trimester each pregnancy to protect the neonate from pertussis.
The authors previously published a smaller study that had shown maternal vaccination for COVID-19 during pregnancy reduced the risk of hospitalization for COVID-19 by 61% during the Delta variant among infants younger than 6 months of age.2 These are the results of a larger follow-up study that also included the Omicron variant. In this case control study, the authors compared infants younger than 6 months of age who were admitted to the hospital with COVID-19 infection and compared them to control infants who were hospitalized for other reasons and assessed exposure to maternal vaccination during pregnancy.
Infants were identified between July 1, 2021, and March 8, 2022, through a network of 30 pediatric hospitals across 22 states in the Centers for Disease Control and Prevention (CDC)-funded Overcoming COVID-19 network. Case infants had to have COVID-19 as the primary reason for admission or with a clinical syndrome that was consistent with acute COVID-19 and a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen test within 10 days after the onset of symptoms or within 72 hours after hospital admission. The control infants were hospitalized infants younger than 6 months of age who had a negative SARS-CoV-2 PCR or antigen test, but they could have had COVID-19-associated symptoms. Matching control infants were enrolled with a date of hospital admission that was within four weeks before or after the admission of the case infant.
Maternal vaccination was defined as completion of a two-dose series of messenger ribonucleic acid (mRNA) vaccine during pregnancy. Women who received the first dose before pregnancy and the second dose during pregnancy could be included. Case infants born to mothers who had been vaccinated fewer than 14 days before delivery were excluded because protective immunity is not achieved until approximately two weeks after vaccination.
Booster doses were not included in the study. Parents were asked about vaccination status and state registries, and the electronic medical record was searched to confirm vaccine status. Data on the infants’ hospitalization and outcomes were collected.
Over the course of the study, the authors enrolled a total of 537 case infants and 512 control infants. With a median age of 2 months in both groups, 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against COVID-19 during pregnancy. Ninety-three percent of the vaccine dates were confirmed for the mothers. The disease severity among case infants included 21% receiving intensive care and 12% who received mechanical ventilation or vasoactive infusions. Two case infants died from COVID-19 and two case infants required extracorporeal membrane oxygenation (ECMO); none of these infants’ mothers had been vaccinated during pregnancy.
The calculated effectiveness of maternal vaccination against hospitalization for COVID-19 among infants was as follows: 52% (95% confidence interval [CI], 33% to 65%) overall, 80% (95% CI, 60% to 90%) during the Delta variant period, 38% (95% CI, 8% to 58%) during the Omicron variant period, 70% (95% CI, 42% to 85%) against admission to an intensive care unit (ICU), 47% (95% CI, 25% to 62%) against non-ICU hospitalization, 69% (95% CI, 50% to 80%) when maternal vaccination occurred after 20 weeks of pregnancy, and 38% (95% CI, 3% to 60%) when maternal vaccination occurred during the first 20 weeks of pregnancy.
COMMENTARY
The current study demonstrates benefits to the young infant when the mother is vaccinated against COVID-19 during pregnancy. The reason for this is the transfer of maternal antibodies to the fetus via the placenta and the sustained level of antibodies in the newborn up to 6 months of age.1 This type of protection also is seen for pertussis and influenza. The authors speculated that the decreased protection seen for the Omicron variant may be solved by booster vaccine doses, as is the strategy among the general population. The study design has many strengths as a national study with excellent data capture. However, limitations include an inability to assess for past maternal COVID-19 infection as well as other confounding factors, such as behavior differences between vaccinated and unvaccinated mothers that might have influenced the risk of infection among infants.
According to the CDC, by the end of 2021, approximately 40% of pregnant patients had been fully vaccinated against COVID-19.3 This is lower than the rates of vaccination in the general population. The World Health Organization, CDC, American College of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal Medicine (SMFM), all strongly encourage COVID-19 vaccination and consider the vaccine safe for those who are considering pregnancy, are pregnant, or are breastfeeding. COVID-19 infection among pregnant individuals has been shown to have an increased risk for severe illness and hospitalization compared to nonpregnant patients. The CDC considers pregnancy an “increased risk” category for severe COVID-19.4 The best way to prevent maternal illness is vaccination. There is no evidence that the COVID-19 vaccines cause miscarriage, congenital anomalies, preterm birth, or stillbirth.
Current recommendations are that pregnant individuals receive the vaccine regardless of trimester if they have not already been vaccinated. Additionally, a booster shot at least five months after the primary series for mRNA-based vaccines (Pfizer or Moderna) and at least two months after vaccination with the Janssen/Johnson & Johnson vaccine is recommended.4 The booster dose can be given during any trimester as well. According to SMFM the benefits of maternal vaccination in preventing maternal hospitalization are high, and vaccination should not be postponed to the third trimester for any potential fetal benefit. Therefore, although the results of this study showing that protection for neonates was higher if the vaccine was given after 20 weeks of pregnancy are intriguing, currently there is no compelling evidence to alter the timing recommendations of the COVID-19 vaccine. Certainly, preventing maternal illness and death is better for the fetus than a theoretical benefit to the neonate of postponing vaccination to the third trimester. It is possible, though, in the future, that COVID-19 vaccination might be recommended with each pregnancy as it is with the pertussis and influenza vaccines. Speaking with pregnant patients about COVID-19 vaccines and boosters is something that we do every day and that can be challenging among the vaccine-hesitant. Both SMFM and ACOG have guides to help providers with these conversations.5,6
REFERENCES
- Shook LL, et al. Durability of anti-spike antibodies in infants after maternal COVID-19 vaccination or natural infection. JAMA 2022;327:1087-1089.
- Halasa NB, 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;71:264-270.
- Hall S. COVID vaccines safely protect pregnant people: The data are in. Nature. Published Jan. 12, 2022. https://www.nature.com/articles/d41586-022-00031-8
- The Society for Maternal-Fetal Medicine COVID Task Force. COVID-19 and pregnancy: What maternal-fetal medicine specialists need to know. Society for Maternal-Fetal Medicine Updated June 6, 2022. https://s3.amazonaws.com/cdn.smfm.org/media/3559/COVID19-What_MFMs_need_to_know_%286-21-22%29_final.pdf
- Society for Maternal-Fetal Medicine. Provider considerations for engaging in COVID-19 vaccine counseling with pregnant and lactating patients. Updated Jan. 11, 2022. https://s3.amazonaws.com/cdn.smfm.org/media/3290/Provider_Considerations_for_Engaging_in_COVID_Vaccination_Considerations_1-11-22_%28final%29_KS.pdf
- American College of Obstetricians and Gynecologists. COVID-19 vaccines and pregnancy: Conversation guide. https://www.acog.org/covid-19/covid-19-vaccines-and-pregnancy-conversation-guide-for-clinicians#:~:text=Key%20Recommendations,-The%20American%20College&text=ACOG%20recommends%20that%20pregnant%20and,vaccine%20dose%20or%20monovalent%20booster
