Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in Neonatal Cord Blood After Vaccination in Pregnancy

Abstract

BACKGROUND: 

Studies evaluating the safety and efficacy of currently available vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not include pregnant participants. No data are available to counsel on vaccine safety and potential for neonatal passive immunity.

CASE: 

A 34-year-old multigravid patient working in health care received the Pfizer-BioNTech (BNT162b2) mRNA vaccine for SARS-CoV-2 in the third trimester of pregnancy. Uncomplicated spontaneous vaginal delivery of a female neonate with Apgar scores of 9 and 9 occurred at term. The patient's blood as well as neonatal cord blood were evaluated for SARS-CoV-2–specific antibodies. Both the patient and the neonate were positive for antibodies at a titer of 1:25,600.

CONCLUSION: 

In this case, passage of transplacental antibodies for SARS-CoV-2 was shown after vaccination in the third trimester of pregnancy.

In Brief

Vaccination in the third trimester of pregnancy resulted in positive neonatal cord blood antibodies at a high titer.

Teaching Points

1. Pregnant patients have been excluded from SARS-CoV-2 vaccine trials, leading to uncertainty regarding safety, efficacy, and potential for neonatal passive immunity.
2. Vaccination in pregnancy produced a robust immune response for the patient, with subsequent transplacental transfer of neutralizing antibodies.

Newly available vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of great interest to patients and health care professionals. Initial studies of the two currently available mRNA vaccines have shown them to be safe and effective in nonpregnant adults.^1,2 Importantly, pregnant and lactating individuals were excluded from initial safety and efficacy trials, despite data demonstrating higher risks of severe infection and pregnancy-related morbidity and mortality.³ The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine released a joint statement in January 2021 advocating that pregnant individuals at high risk for contracting the virus should be able to decide whether they will receive the vaccination during pregnancy or while breastfeeding.⁴

In addition to safety, the potential for transplacental transfer of neutralizing maternal antibodies is also a consideration. The neonatal period is marked by an immature immune system, making it a vulnerable period for infection. Maternal antibodies generated during pregnancy are able to cross the placenta into the fetal circulation, providing immune protection for the neonate. This has been demonstrated previously in pregnant patients receiving several other vaccines in pregnancy.^4–7

In this case, we report on a pregnant individual who received the Pfizer-BioNTech (BNT162b2) mRNA vaccine for SARS-CoV-2 at 32 weeks of gestation, with documented antibodies present in neonatal cord blood.

CASE

We present the case of a 34-year-old multigravid patient (G4P2012) who works as a nurse in a large health care system. System guidance allowed for pregnant individuals to opt in to receive a vaccine when it was available based on the tier system established by the Centers for Disease Control and Prevention. The patient’s pregnancy was complicated by a history of fetal growth restriction in both prior pregnancies and hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome in one prior pregnancy. Fetal growth was monitored by ultrasonography and was normal throughout the pregnancy.

Vaccination became available when the patient was at 32 weeks of gestation. She received her first dose of the BNT162b2 mRNA vaccine at 32 6/7 weeks of gestation and her second dose at 35 2/7 weeks. She reported no adverse effects from vaccine administration, with the exception of soreness at the injection site.

The patient presented in spontaneous labor at 38 6/7 weeks of gestation. She underwent an unmedicated vaginal delivery without complication. The newborn course was also uncomplicated—the neonate had Apgar scores of 9 and 9 at 1 and 5 minutes, and weight was appropriate for gestational age. Cord blood and maternal blood were obtained and evaluated for the presence of antibodies to SARS-CoV-2. Maternal blood was positive for immunoglobulin G at a titer of 1:25,600. The cord blood was also positive for SARS-CoV-2–specific immunoglobulin G at a titer of 1:25,600.

In the course of her pregnancy, the patient was tested for SARS-CoV-2 infection multiple times by polymerase chain reaction nasal swab. The patient received testing when experiencing any upper respiratory symptoms, occasional asymptomatic surveillance testing, and testing on admission for delivery. She reported no known SARS-CoV-2 exposures. All test results were negative for the presence of SARS-CoV-2 during her pregnancy. A prior antibody test was performed as part of a system-wide effort to determine the incidence of infections among health care professionals, and the results were negative. Table 1 reviews all test results for the patient and the neonate.

Table 1.: Evaluations for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

DISCUSSION

To our knowledge, this is the first case report documenting transplacental transfer of neutralizing SARS-CoV-2 antibodies in the setting of maternal mRNA vaccine administration (PubMed search conducted on February 12, 2021, with the following search terms: “SARS-CoV-2 vaccine in pregnancy” or “COVID-19” or “SARS-CoV-2 vaccine in cord blood”). No apparent complications were noted in the patient or the neonate.

Antibody transfer after vaccination in pregnancy ideally would confer protection for both the pregnant patient and the neonate. Studies evaluating the neonatal immune response to maternal vaccine administration have demonstrated neonatal protection from transplacental antibody transfer for a number of vaccines, including tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (TDaP); influenza virus; and respiratory syncytial virus.^6–9 Our case supports that this may also be true for the SARS-CoV-2 vaccine. Although it is possible that neonatal antibodies were from undetected maternal infection with SARS-CoV-2, this is unlikely given the frequency and high sensitivity of polymerase chain reaction testing in this case.

Transplacental passage of SARS-CoV-2 antibodies after infection in pregnancy has been reported. A recent study evaluating the vertical transmission of SARS-CoV-2 as well as transplacental passage of antibodies after infection in pregnancy showed low rates of vertical transmission of the virus and also low rates of transplacental antibody transfer. The authors conclude that this low rate of antibody transfer may leave neonates susceptible to infection.⁵ Our case suggests that a more robust immune response may be achieved after maternal vaccination than after natural infection with SARS-CoV-2. A prospective trial is currently planned at our institution to compare neonatal immune responses in populations of vaccinated pregnant people and pregnant people with SARS-CoV-2 infection.

Importantly, data surrounding vaccines are frequently generated with the exclusion of pregnant patients. Although pregnancy imparts many ethical dilemmas, the ability of pregnant patients to consent to participate in a clinical trial is not one of them. Recently, many experts have advocated for the inclusion of pregnant patients in clinical research in which the results may be useful in a pregnant population.^10–12 However, Smith et al¹³ found that fewer than 2% of coronavirus disease 2019 (COVID-19) clinical trials listed on international registries included pregnant patients. Given this lack of data, there is understandable confusion over whether pregnant people should be vaccinated. Additional evidence related to transplacental antibody transfer, as well as other risks and benefits of SARS-CoV-2 vaccination in pregnancy, will allow patients to make informed choices regarding vaccination. Inclusion of pregnant people in future clinical studies is critical.