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

Abstract

IMPORTANCE BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in the third trimester was found to be associated with a strong maternal humoral IgG response that crossed the placenta and approached maternal titers in the newborn.OBJECTIVE To evaluate maternal and neonatal SARS-CoV-2 immunoglobulin G (IgG) antibody levels at birth after mRNA COVID-19 vaccination during the second trimester of pregnancy. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study, conducted at a single medical center in Haifa, Israel, from May to July 2021, included women with a singleton pregnancy over 24 weeks of gestation at least 7 days after receipt of their second COVID-19 vaccine dose who were not known to be previously infected with COVID-19.EXPOSURES BNT162b2 (Pfizer/BioNTech) vaccination. MAIN OUTCOMES AND MEASURESThe primary outcomes were SARS-CoV-2 IgG antibody titers measured in the parturient at admission and in the umbilical cord blood within 30 minutes after delivery. Secondary outcomes were the correlation between antibody titers, feto-maternal characteristics, maternal adverse effects after vaccination, and time interval from vaccination to delivery. RESULTS Antibody levels were measured for 129 women (mean [SD] age, 31.9 [4.9] years) and 114 neonates, with 100% of the tests having positive results. The mean (SD) gestational age at administration of the second vaccine dose was 24.9 (3.3) weeks. Neonatal IgG titers were 2.6 times higher than maternal titers (median [range], 3315.7 [350.1-17 643.5] AU/mL vs 1185.2 [146.6-32 415.1] AU/mL). A positive correlation was demonstrated between maternal and neonatal antibodies (r = 0.92; 95% CI, 0.89-0.94). Multivariable analysis revealed that for each week that passed since receipt of the second vaccine dose, maternal and neonatal antibody levels changed by −10.9% (95% CI, −17.2% to −4.2%; P = .002) and −11.7% (95% CI, −19.0 to −3.8%; P = .005), respectively. For each 1-year increase in the mother's age, maternal and neonatal antibody levels changed by −3.1% (95% CI, −5.3% to −0.9%; P = .007) and −2.7% (95% CI, −5.2% to −0.1%; P = .04), respectively. CONCLUSIONS AND RELEVANCEIn this cohort study, receipt of the BNT162b2 mRNA COVID-19 vaccine during the second trimester of pregnancy was associated with maternal and neonatal humoral responses, as reflected in maternal and neonatal SARS-CoV-2 IgG antibody levels measured after delivery. These findings support COVID-19 vaccination of pregnant individuals during the second trimester to achieve maternal protection and newborn safety during the pandemic.

Effectiveness and Safety of COVID-19 Vaccine among Pregnant Women in Real-World Studies: A Systematic Review and Meta-Analysis

“…In addition, studies have found that Pfizer vaccine can induce effective maternal to neonatal transfer of IgG [29,43,62]. The longer the time interval from vaccination to delivery, the higher the maternal and neonatal antibody levels and the cord-to-maternal ratio [63,64]. After the receipt of the second vaccine dose, the maternal and neonatal antibody levels change by −10.9% and −11.7% per week [63].…”

“…The longer the time interval from vaccination to delivery, the higher the maternal and neonatal antibody levels and the cord-to-maternal ratio [63,64]. After the receipt of the second vaccine dose, the maternal and neonatal antibody levels change by −10.9% and −11.7% per week [63]. This suggests that maternal vaccination protects infants.…”

Third trimester messenger RNA COVID-19 booster vaccination upsurge maternal and neonatal SARS-CoV-2 immunoglobulin G antibody levels at birth

“…The correlation between antibody titers, feto-maternal characteristics, and the time interval from vaccination to delivery were analyzed after the completion of data gathering. Maternal and neonatal IgG antibodies from the current study were compared to antibody levels measured after second trimester 2-dose vaccination in a previous study published by our group [14] . In addition, transplacental SARS-CoV-2 IgG antibody transfer ratios were calculated by dividing neonatal (umbilical cord blood) IgG levels, by the IgG antibody levels in paired maternal blood.…”

Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy

“…Circulating anti-S1 RBD antibody is also only one measure of immune protection and does not account for aspects of immunologic memory. Although we did not specifically measure neutralizing antibody, anti-S IgG correlates closely with neutralizing activity patterns 16,38 .…”

“…Yang et al found that early third trimester vaccination led to highest anti-spike IgG levels 31 . Kugelman et al reported that second trimester mRNA vaccination led to protective IgG levels at delivery 38 , while Rottenstreich et al reported that IgG levels were lowest after first trimester and highest after 3 rd trimester vaccination 32 . Our data, although limited to second and third trimester vaccination, shows clear evidence that vaccination results in superior antibody levels and transfer ratios compared to infection, and that this difference is pronounced with longer latency.…”