P-450 Maternal-fetal SARS-CoV-2 antibody transfer in relation to the trimester of infection
Authors: Fich L , Vauvert K , Hviid R , Aabakke A , Kelstrup L , Clausen T , Vinter C , Vestgaard M , Farlie R , Sørensen A , Sundtoft I , Godtfredsen A , Burmester L , Jørgensen F , Freiesleben N , Nielsen H 
Published: July 2024

Abstract

Study question
What does the maternal-fetal SARS-CoV-2 antibody transfer look like depending on the trimester of infection?

Summary answer
There is a statistically significant tendency for newborns of SARS-CoV-2 positive mothers to have a higher IgG antibody level compared to their mother’s at delivery.

What is known already
Passive maternal-fetal transfer of SARS-CoV-2 antibodies has been demonstrated, whilst the degree of transfer depending on the trimester of infection is lacking, and so far, there is no stratification on all three trimesters of SARS-CoV-2 infection in relation to maternal antibody levels in SARS-CoV-2 positive women, and the degree of transfer of SARS-CoV-2 antibodies to the newborn. It is known that for perinatal infections such as Rubella and Toxoplasmosis the timing of infection related to gestational age is crucial for the severity of fetal/obstetric outcomes, hence the trimester of SARS-CoV-2 infection could potentially be crucial.

Study design, size, duration
This is a large prospective cohort study with full medical record of all 3,026 participating women and 3,073 of their newborns, as well as antibody measurements on all women who participated between April 4’th 2020 until April 30’st 2021. Of the 3,026 participating women 459 were SARS-CoV-2 positive.

Participants/materials, setting, methods
The positive cohort consisted of women who had a positive SARS-CoV-2 PCR test, antigen test or antibody test and participated with a maternal blood sample and an umbilicalcord blood sample at delivery. The negative cohort was established at Hvidovre Hospital (CHH), where all women with a first trimester double marker blood test taken at CHH could participate, all woman attending their second trimester ultrasound or giving birth were invited to participate with a blood sample.

Main results and the role of chance
This prospective cohort study found a strong and statistically significant tendency for newborns of SARS-CoV-2 positive mothers to have a higher IgG antibody level compared to their mother’s IgG antibody level at delivery. In total, 87.5%, 95.3% and 60.3% of newborns of women who tested positive in their first, second and third trimester respectively, had higher IgG antibody levels than their mother’s at delivery. The higher level of antibodies in the newborns’ cord blood compared to their mother’s demonstrated in this study, correlates with findings of for instance pertussis toxin antibodies during pregnancy and aligns with general findings on maternofetal transport of immunoglobins. Our findings indicates that the fetus is either able to concentrate antibody levels or maintain the level of IgG antibodies transferred.

Limitations, reasons for caution
With only 40 women being SARS-CoV-2 positive in their first trimester, analysis in this group should be taken with caution. Other limitations are the 56 newborns of positive women who did not have an umbilical cord blood sample taken due to PPH, acute cesarean section or blood sample coagulated.

Wider implications of the findings
This knowledge of the maternal-fetal antibody transmission pattern is valuable for the basic understanding of SARS-CoV-2 in pregnancy and for future investigation on expected degree of early life protection against SARS-CoV-2 but could also be of interest if investigating the paradoxically concept of blunting when considering vaccination of neonates.

Trial registration number
H-20022647