Abstract
Background
The survival of antibody isotypes specific to pertussis toxin (PT) and filamentous hemagglutinin (FHA) from mother’s own milk (MBM) and donor breast milk (DBM) during preterm infant digestion was investigated.
Methods
Feed, gastric, and stool samples were collected from 20 preterm mother–infant pairs at 8–9 days and 21–22 days postpartum. Samples were analyzed via ELISA for anti-FHA or anti-PT immunoglobulin A (IgA), IgM, and IgG.
Results
Anti-PT IgA, anti-FHA IgG, and anti-PT IgG were lower in MBM than DBM at 8–9 days postpartum, whereas anti-FHA IgM was higher in MBM than DBM. Anti-PT IgA, anti-PT IgG, and anti-FHA IgG in DBM decreased in gastric contents at both postpartum times but those antibodies in MBM were stable or increased during gastric digestion. Anti-FHA-specific IgA and IgM were higher in gastric contents from infants fed MBM than from infants fed DBM at 8–9 days. All pertussis antibodies were detected in infant stools at both postpartum times.
Conclusions
Pertussis-specific antibodies from MBM were stable during infant digestion, whereas anti-pertussis IgA and IgG from DBM decreased in gastric contents. The constant region and variable region of antibodies and maternal immunization appear to be the critical factors for their stability to proteolytic digestion and pasteurization.
Impact
-
Pertussis-specific antibodies from mother’s breast milk were stable during infant digestion, whereas anti-pertussis IgA and IgG from donor breast milk decreased in gastric contents.
-
The constant region and variable region of pertussis-specific antibodies and the maternal immunization (previous infections and vaccinations) appear to be the critical factors for their stability to proteolytic digestion and pasteurization.
-
Pertussis-specific antibodies from either mother’s breast milk or donor breast milk survived during preterm infant digestion and both types of milk will compensate for the lower IgG transplacental transfer in preterm infants compared with term infants.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Cohen, M. B. Etiology and mechanisms of acute infectious diarrhea in infants in the United States. J. Pediatr. 118, S34–S39 (1991).
Demers-Mathieu, V. et al. Differences in maternal immunoglobulins within mother’s own breast milk and donor breast milk and across digestion in preterm infants. Nutrients 11, 920 (2019).
Demers-Mathieu, V. et al. Antenatal influenza A-specific IgA, IgM, and IgG antibodies in mother’s own breast milk and donor breast milk, and gastric contents and stools from preterm infants. Nutrients 11, 1567 (2019).
Roos, N. et al. 15N-labeled immunoglobulins from bovine colostrum are partially resistant to digestion in human intestine. J. Nutr. 125, 1238–1244 (1995).
Eibl, M. M., Wolf, H. M., Fürnkranz, H. & Rosenkranz, A. Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA–IgG feeding. N. Engl. J. Med. 319, 1–7 (1988).
Bakker‐Zierikzee, A. M. et al. Faecal SIgA secretion in infants fed on pre‐or probiotic infant formula. Pediatr. Allergy Immunol. 17, 134–140 (2006).
Schanler, R. J., Goldblum, R. M., Garza, C. & Goldman, A. S. Enhanced fecal excretion of selected immune factors in very low birth weight infants fed fortified human milk. Pediatr. Res. 20, 71 (1986).
Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months-Advisory Committee on Immunization Practices (ACIP), 2011. Morb. Mortal. Wkly Rep. 60, 1424–1426 (2011).
Centers for Disease Control and Prevention. Pertussis (whooping cough)—what you need to know. http://www.cdc.gov/Features/Pertussis/ (2012).
Healy, C. M., Rench, M. A. & Baker, C. J. Importance of timing of maternal combined tetanus, diphtheria, and acellular pertussis (Tdap) immunization and protection of young infants. Clin. Infect. Dis. 56, 539–544 (2012).
Halperin, B. et al. Kinetics of the antibody response to tetanus-diphtheria-acellular pertussis vaccine in women of childbearing age and postpartum women. Clin. Infect. Dis. 53, 885–892 (2011).
Sweet, C., Jakeman, K. J. & Smith, H. Role of milk-derived IgG in passive maternal protection of neonatal ferrets against influenza. J. Gen. Virol. 68, 2681–2686 (1987).
Ogra, S. S., Weintraub, D. & Ogra, P. L. Immunologic aspects of human colostrum and milk: III. Fate and absorption of cellular and soluble components in the gastrointestinal tract of the newborn. J. Immunol. 119, 245–248 (1977).
Raya, B. A. et al. The induction of breast milk pertussis specific antibodies following gestational tetanus–diphtheria–acellular pertussis vaccination. Vaccine 32, 5632–5637 (2014).
De Schutter, S. et al. Quantification of vaccine-induced antipertussis toxin secretory IgA antibodies in breast milk: comparison of different vaccination strategies in women. Pediatr. Infect. Dis. J. 34, e149–e152 (2015).
van den Berg, J. P. et al. Transplacental transport of IgG antibodies specific for pertussis, diphtheria, tetanus, Haemophilus influenzae type b, and Neisseria meningitidis serogroup C is lower in preterm compared with term infants. Pediatr. Infect. Dis. J. 29, 801–805 (2010).
Langkamp, D. L., Hoshaw-Woodard, S., Boye, M. E. & Lemeshow, S. Delays in receipt of immunizations in low-birth-weight children: a nationally representative sample. Arch. Pediatr. Adolesc. Med. 155, 167–172 (2001).
Decarlo, J., Tramer, A. & Startzman, H. Iodized oil aspiration in the newborn. Am. J. Dis. Child. 84, 442–445 (1952).
Sagrera, X. et al. Outbreaks of influenza A virus infection in neonatal intensive care units. Pediatr. Infect. Dis. J. 21, 196–200 (2002).
Carroll, K. & Herrmann, K. R. The cost of using donor human milk in the NICU to achieve exclusively human milk feeding through 32 weeks postmenstrual age. Breastfeed. Med. 8, 286–290 (2013).
Evans, T. J., Ryley, H. C., Neale, L. M., Dodge, J. A. & Lewarne, V. M. Effect of storage and heat on antimicrobial proteins in human milk. Arch. Dis. Child. 53, 239–241 (1978).
Ford, J. E., Law, B. A., Marshall, V. M. & Reiter, B. Influence of the heat treatment of human milk on some of its protective constituents. J. Pediatr. 90, 29–35 (1977).
Demers-Mathieu, V., Underwood, M., Beverly, R., Nielsen, S. & Dallas, D. Comparison of human milk immunoglobulin survival during gastric digestion between preterm and term infants. Nutrients 10, 631 (2018).
Demers-Mathieu, V., Nielsen, S. D., Underwood, M. A., Borghese, R. & Dallas, D. C. Changes in proteases, antiproteases and bioactive proteins from mother’s breast milk to the premature infant stomach. J. Pediatr. Gastroenterol. Nutr. 66, 318–324 (2018).
Boes, M. Role of natural and immune IgM antibodies in immune responses. Mol. Immunol. 37, 1141–1149 (2000).
Zimmermann, P. & Curtis, N. Factors that influence the immune response to vaccination. Clin. Microbiol. Rev. 32, e00084 (2019).
Kollmann, T. R., Kampmann, B., Mazmanian, S. K., Marchant, A. & Levy, O. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity 46, 350–363 (2017).
Acknowledgements
We thank the Northwest Mother’s Milk Bank for their support. This study was funded by the K99/R00 Pathway to Independence Career Award, Eunice Kennedy Shriver Institute of Child Health & Development of the National Institutes of Health (R00HD079561), and The Gerber Foundation.
Author information
Authors and Affiliations
Contributions
V.D.-M., D.C.D., and R.K.H. designed the clinical study. V.D.-M. conducted the experiments and the statistical analyses and wrote the paper. R.K.H., A.M.M., E.A.M., and R.L.M. provided milk and gastric samples and revised the paper. All authors revised the paper.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Demers-Mathieu, V., Huston, R.K., Markell, A.M. et al. Impact of pertussis-specific IgA, IgM, and IgG antibodies in mother’s own breast milk and donor breast milk during preterm infant digestion. Pediatr Res 89, 1136–1143 (2021). https://doi.org/10.1038/s41390-020-1031-2
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41390-020-1031-2


