The COVID-19 pandemic of 2019 (COVID-19) increased the risk of severe illness and death in several categories, including very young infants and pregnant women. The introduction of effective vaccines at the end of 2020 should prevent severe illness and death even after acute infection. During this time, vaccination during pregnancy was recommended to protect the mother and child through the transplacental delivery of antibodies.
The differences in protection provided by maternal COVID-19 vaccination to preterm and full-term infants, however, remain unclear. A new study published in JAMA Network Open reports on the concentration of maternal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in prematurely born infants.
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How has COVID-19 protected pregnant mothers?
COVID-19 vaccines have successfully reduced the incidence of severe illness and death related to the disease during pregnancy. Compared to the increased rates observed with COVID-19 during pregnancy, outcomes such as hospitalizations, intensive care unit (ICU) admissions, and deaths have significantly decreased with vaccination.
Previous studies have shown that vaccinated pregnant women have a lower risk of illness, hospitalizations, ICU admissions, stillbirths, and neonatal deaths compared to unvaccinated pregnant women. The vaccine-induced antibodies primarily target the viral spike antigen and pass through the placenta via active transfer.
Fetal blood contains steadily increasing concentrations of maternal immunoglobulin-G antibodies (IgG), which are passed through the placenta, going from 10% of the maternal concentration in mid-pregnancy to 50% in the 28th-32nd week. A maternal COVID-19 vaccination may protect the baby from severe COVID-19 illness; however, there is still a lack of data confirming whether maternal vaccination delivers adequate amounts of protective anti-spike antibodies in preterm infants.
About the Study
The aim of the current study was to measure the anti-spike antibody levels in umbilical cord blood samples from preterm and full-term births and compare them with maternal blood samples. The study included a prospective cohort of pregnant women from whom blood samples and umbilical cord blood samples of their newly delivered infants were obtained between February 2021 and January 2023.
All participants received two or more doses of a messenger ribonucleic acid (mRNA) COVID-19 vaccine before delivery. None of the study participants had a current or prior COVID-19 infection.
What did the Study Find?
Of the 220 participants with an average age of 34 years, there were 36 preterm births and 184 full-term births. Over 80% of the study participants were white, 12% were Asian, and 2% and 6% were Black and Hispanic, respectively.
Women with preterm births had a higher body mass index (BMI) of around 32 compared to 30 for women with full-term births. Women with higher BMIs were also associated with an increased risk of preconception diabetes, preeclampsia, and chronic hypertension.
The mean gestational age for preterm births was 35 weeks compared to 39.5 weeks for full-term births. Approximately 66% of preterm infants were delivered by cesarean section, compared to 33% of full-term infants.
About 120 and 100 women received two and three vaccine doses before delivery, respectively. Of those delivering preterm infants, about 70% received three or more vaccine doses, compared to 40% in full-term births.
The time from the last vaccine dose to delivery was approximately 16 weeks, with the median gestational age at the time of the last dose being 25 weeks for both preterm and full-term pregnancies.
The concentration of anti-spike antibodies in maternal blood was 674 with two doses and over 8,169 with three or more doses. The corresponding concentrations in umbilical cord blood samples were around 1,000 and approximately 10,000.
The levels of antibodies in maternal blood were higher in pregnancies that ended prematurely than in full-term births. However, the antibody levels in umbilical cord blood in preterm infants were lower, leading to a lower ratio of umbilical cord to maternal antibodies in preterm births.
This difference between pregnancies ending in full-term and preterm births was not observed in either maternal antibody levels or umbilical cord blood to maternal blood antibody ratios when considering the timing of vaccination during pregnancy. The peak value was observed around 10 weeks after the last vaccine dose.
After adjusting for the timing of vaccination and the number of vaccine doses, there was no association between preterm birth and antibody levels.
What are the Implications?
The levels of antibodies in umbilical cord blood were ten times higher in infants of women who received at least three doses of a COVID-19 mRNA vaccine compared to those who received two doses. However, this finding did not correlate with gestational age at delivery. Furthermore, there was no significant difference in umbilical cord blood antibody levels between preterm and full-term births.
While previous reports have indicated a correlation between three or more vaccine doses and higher antibody concentrations, this is the first time this has been compared between preterm and full-term infants.
Despite lower rates of antibody transmission in preterm infants, an increased number of vaccine doses before delivery may improve the final concentration of umbilical cord blood antibodies. Therefore, it is recommended to administer the booster dose in women at risk of preterm birth before the third trimester, while others may receive it around 10 weeks before the expected due date.
„Maternal antibody concentrations appeared to be more important for determining umbilical cord antibody concentrations than gestational age at delivery.“