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

Abstract

Antenatal milk anti-influenza antibodies may provide additional protection to newborns until they are able to produce their own antibodies. To evaluate the relative abundance of milk, we studied the antibodies specific to influenza A in feeds and gastric contents and stools from preterm infants fed mother's own breast milk (MBM) and donor breast milk (DBM). Feed (MBM or DBM) and gastric contents (MBM or DBM at 1 h post-ingestion) and stool samples (MBM/DBM at 24 h post-ingestion) were collected, respectively, from 20 preterm (26-36 weeks gestational age) mother-infant pairs at 8-9 days and 21-22 days of postnatal age. Samples were analyzed via ELISA for anti-H1N1 hemagglutinin (anti-H1N1 HA) and anti-H3N2 neuraminidase (anti-H3N2 NA) specificity across immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) isotypes. The relative abundance of influenza A-specific IgA in feeds and gastric contents were higher in MBM than DBM at 8-9 days of postnatal age but did not differ at 21-22 days. Anti-influenza A-specific IgM was higher in MBM than in DBM at both postnatal times in feed and gastric samples. At both postnatal times, anti-influenza A-specific IgG was higher in MBM than DBM but did not differ in gastric contents. Gastric digestion reduced anti-H3N2 NA IgG from MBM at 21-22 days and from DBM at 8-9 days of lactation, whereas other anti-influenza A antibodies were not digested at either postnatal times. Supplementation of anti-influenza A-specific antibodies in DBM may help reduce the risk of influenza virus infection. However, the effective antibody dose required to induce a significant protective effect remains unknown.

Keywords: flu vaccine; human milk; lactation; maternal immunoglobulins; passive immunization; prematurity.

Figure 1

Schema of study design to determine the difference of antenatal influenza-specific antibodies in mother’s breast milk (MBM) and donor breast milk (DBM) in gastric contents and stool samples from preterm infants.

Figure 2

Milk antibodies specific to anti-H1N1 hemagglutinin (anti-H1N1 HA) in mother’s own breast milk (MBM) and donor breast milk (DBM) feeds, and gastric samples from preterm infants fed MBM and DBM (26–36 wk of GA). Relative abundance of (A) anti-H1N1 HA IgA, (B) anti-H1N1 HA IgM, and (C) anti-H1N1 HA IgG at 8–9 days of postnatal age. Relative abundance (EU/mL) of (D) anti-H1N1 HA IgA, (E) anti-H1N1 HA IgM, and (F) anti-H1N1 HA IgG at 21–22 days of postnatal age. Values are min, max, and median, n = 20 for 8–9 days and n = 16 for 21–22 days of postnatal age. Asterisks show statistically significant differences between variables (*** p < 0.001; ** p < 0.01) using the Wilcoxon matched-pairs signed-rank test.

Figure 3

Milk antibodies specific to anti-H3N2 neuraminidase (anti-H3N2 NA) in mother’s own breast milk (MBM) and donor breast milk (DBM) feeds, and gastric samples from preterm infants fed MBM and DBM (26–36 wk of GA). Relative abundance of (A) anti-H3N2 NA IgA, (B) anti-H3N2 NA IgM, and (C) anti-H3N2 NA IgG at 8–9 d postnatal age. Relative abundance (EU/mL) of (D) anti-H3N2 NA IgA, (E) anti-H3N2 NA IgM, and (F) anti-H3N2 NA IgG at 21–22 days of postnatal age. Values are min, max, and median, n = 20 for 8–9 days and n = 16 for 21–22 days of postnatal age. Asterisks show statistically significant differences between variables (*** p < 0.001; ** p < 0.01; * p < 0.05) using the Wilcoxon matched-pairs signed-rank test.

Figure 4

Comparison of immunoglobulin relative abundance between raw human milk (RHM) and pasteurized whole human milk (PWHM) or pasteurized skimmed human milk (PSHM) (n = 3). Relative abundance of anti-H1N1 HA (A) IgA, (B) IgM, (C) IgG, and of anti-H3N2 NA. (D) IgA, (E) IgM, and (F) IgG in mother’s milk. Milk samples were from one mother who delivered one term infant at 38 wk of GA and collected milk at 12 days of postnatal age. Asterisks show statistically significant differences between variables (*** p < 0.001; ** p < 0.01; * p < 0.05) using one-way ANOVA followed by Dunnett’s multiple comparisons test.