Persistence of COVID-19 Human Milk Antibodies After Maternal COVID-19 Vaccination: Systematic Review and Meta-Regression Analysis.

The World Health Organization (WHO) declared COVID-19 a pandemic. The Centers for Disease Control and Prevention (CDC), WHO, and American College of Obstetricians and Gynecologists (ACOG) recommend vaccination of pregnant and lactating women, aiming to protect both mothers and their infants through transplacental and human milk antibody transmission. This study aims to assess the quantity of antibodies in human milk and determine the effect of time, vaccine type, and dose on antibody level. Single-arm prospective observational studies reporting the COVID-19-specific antibody level in human milk after COVID-19 vaccination during pregnancy or lactation were included. PubMed, Scopus, Cochrane, EBSCO, and Web of Science were searched from December 2019 to November 22, 2022. Data were extracted in a uniform Google sheet. A total of 2657 studies were identified. After the removal of duplicates and screening, 24 studies were included in the systematic review and meta-regression. Human milk COVID-19-specific antibody levels increased with subsequent vaccine doses, as reflected by a positive relationship for the second (coefficient=0.91, P-value 0.043 for IgA and coefficient=1.77, P-value 0.009 for IgG) and third (coefficient=1.23, P-value 0.0029 for IgA and coefficient=3.73, P-value 0.0068 for IgG) doses. The antibody level exhibited a weak positive relationship with the follow-up time (coefficient=0.13, P-value 0.0029 for IgA and coefficient=0.18, P-value 0.016 for IgG). Only one of the 38 infants showed detectable COVID-19 IgM and IgA antibody levels in their blood. There was an increase in the neutralizing activity of COVID-19 antibodies in human milk following the COVID-19 vaccination. From the analysis of published data, we found high positive levels of antibodies in human milk that increased with subsequent doses. Additionally, the human milk antibodies exhibit a positive neutralizing effect. Only one infant had detectable COVID-19 IgM+IgA antibodies in the blood. Further research is needed to discuss infant protection through a mother's vaccination.