Infant Serum Samples Research Articles

Lymphocytic Choriomeningitis Virus Infections in Hungary between 2017-2023-Investigation of the First Congenital Infections.

Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne arenavirus, primarily spread by common house mouse species. Acquired human infections range from asymptomatic to mild flu-like symptoms and self-resolving neurological diseases. In contrast, intrauterine LCMV infection is associated with high mortality and morbidity. Infection of the fetus often leads to fetal death, and surviving fetuses may develop vision impairment and central nervous system developmental disorders. LCMV is mainly diagnosed by serological methods using in-house indirect immunofluorescence assays. LCMV nucleic acid is detected by the nested RT-PCR method and confirmed by Sanger sequencing. In Hungary, 23 acquired lymphocytic choriomeningitis cases were diagnosed between 2017 and 2023. Ten out of 23 confirmed patients proved to be positive by the PCR method. Two cases of intrauterine LCMV infections were detected in 2019 and 2021, respectively. The IgG antibody titers measured in the infant's serum samples were much higher than the IgG titers of the maternal serum samples. Both IgM and IgA antibodies were detectable in the infants' sera. As the microbiological diagnosis of LCMV is rather challenging and the symptoms are very similar to the clinical picture of other common teratogenic pathogens such as cytomegalovirus or Toxoplasma gondii, intrauterine LCMV infections might still be underdiagnosed.

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula.

Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals.

Congenital cytomegalovirus infection in newborns suspected of congenital rubella syndrome in Iran: a cross-sectional study

BackgroundFollowing rubella virus control, the most important cause of congenital infections is human cytomegalovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non-primary maternal infections. The present study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran.MethodsOut of 1629 collected infants' serum samples suspected of CRS but negative for rubella IgM, 524 samples were selected regarding cCMV complications. These samples were divided into two age groups: 1- one month and younger, 2- older than 1 month up to one year. Anti-HCMV IgM detection was performed on these serums. Then HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results in IgM detection.ResultsHerein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM, 12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one month to one year was 14.5%. Identified genotypes in this study were gB-1(63.63%), gB2 (18.18%), and gB3 (18.18%), respectively.ConclusionsThis comprehensive study was performed on serum samples of symptomatic infants clinically suspected of cCMV from all over Iran. There was a good correlation between serology findings and PCR.

The comparison of skin prick test, serological specific IgE test and solid phase immunoassay in the diagnosis of infantile allergic diseases.

This retrospective study was designed in order to compare the usefulness of skin prick tests, serological specific IgE tests and solid phase immunoassays in the diagnosis of infantile allergic diseases. Two hundred infants with allergic diseases (120 infants with eczema and 80 infants with asthma), diagnosed in the Pediatric Clinic of our hospital between June of 2011 and June of 2016, were selected to participate in the study. 100 healthy infants were included in a control group. All infants received a skin prick test, a serological specific IgE test or a solid phase immunoassay. A total of 38 allergens were used for the infants receiving skin prick test. The IgE in the serum samples of infants was detected by immunoblotting. And, allergens were detected by solid phase immunoassay in the infants receiving solid phase immunoassay. The positive predictive value, negative predictive value, specificity and sensitivity for these 3 diagnostic methods were analyzed after generating a ROC curve. In the eczema group, the AUCs (the area under the ROC curve) for skin prick test, serological specific IgE test and solid phase immunoassay were 0.8685±0.0187, 0.8137±0.024 and 0.9682±0.0358, respectively. The sensitivities for skin prick test, serological specific IgE test and solid phase immunoassay were 85.70%, 83.62% and 88.72%, respectively. And, the specificities were 74%, 68% and 83%, respectively. The positive predictive values were 87.27%, 92.37% and 90.00%; and the negative predictive values were 57.04%, 51.11% and 78.15%, respectively. In the asthma group, the AUCs for skin prick test, serological specific IgE test and solid phase immunoassay were 0.8186±0.0161, 0.8037±0.0241 and 0.952±0.0421, respectively. The sensitivities for skin prick test, serological specific IgE test and solid phase immunoassay were 84.70%, 88.62% and 96.72%, respectively. The specificities were 76%, 64% and 81%, respectively; the positive predictive values were 81.34%, 85.59% and 84.54%, respectively. The negative predictive values were 69.29%, 67.14% and 70.08%, respectively. While all three methods were effective in the diagnosis of infantile allergic diseases, the solid phase immunoassay was superior to the other two methods, as evidenced by the obtained values and we recommend it for clinical application as a goal standard.

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.

Association of infant Rib and Alp1 surface protein N-terminal domain immunoglobulin G and invasive Group B Streptococcal disease in young infants.

Vaccine development for Group B Streptococcus (GBS), a common cause of invasive disease in early-infancy and adverse pregnancy outcomes, include exploring widely-expressed GBS surface proteins as vaccine epitopes. We investigated the association between natural infant serum IgG against the RibN and Alp1N domains and risk of invasive GBS disease caused by isolates expressing these proteins. We analyzed maternal and infant serum samples from GBS disease cases and infants born to GBS-colonized women controls. Bayesian modelling was used to calculate the GBS homotypic IgG concentration associated with risk reduction of invasive disease in the infant. PCR-based typing of 85 GBS invasive isolates showed 46 and 24 possessing the gene for Rib and Alp1, respectively. These were matched to 46 and 36 infant controls whose mothers were colonized with GBS expressing Rib and Alp1, respectively. RibN IgG geometric mean concentrations (GMC) were lower in cases than controls among infants (0.01; 95%CI: 0.01-0.02 vs 0.04; 95%CI: 0.03-0.06; p<0.001), no significant difference was found between maternal RibN IgG GMC in cases compared to controls. Alp1N IgG GMC was also lower in infant cases (0.02; 95%CI: 0.01-0.03) than controls (0.05; 95%CI: 0.04-0.07; p<0.001); albeit not so in mothers. An infant IgG threshold≥0.428 and≥0.112µg/mL was associated with 90% risk reduction of invasive GBS disease due to Rib and Alp1 expressing strains, respectively. Lower serum RibN and Alp1N IgG GMC were evident in infants with invasive GBS disease compared with controls born to women colonized with GBS expressing the homotypic protein. These data support the evaluation of Alp family proteins as potential vaccine candidates against invasive GBS disease.

The value of plasma insulin-like growth factor 1 and interleukin-18 in the diagnosis of bronchopulmonary dysplasia in premature infants.

ObjectiveTo explore the diagnostic value of IGF-1 and IL-18 in premature infants with BPD.MethodsThrough a prospective observational study, the serum samples of infants in the BPD group and the non-BPD group were collected at different targeted time points, and the serum IGF-1 and IL-18 concentrations were dynamically monitored by ELISA. The Student t-test and one-way analysis of variance were adopted to analyze data, and the receiver operating characteristic (ROC) curve was used to test the diagnostic value.ResultA total of 90 VLBW premature infants admitted to NICU between January 2020 and 2021 were finally included. Compared with the non-BPD group, infants diagnosed with BPD had a significantly lower serum concentration of IGF-1 (P < 0.05) but a higher level of IL-18 (P < 0.05) on days 1, 7, 14, and 28 after birth. With the ROC curve analysis, the serum concentration IGF-1 on day 14 and IL-18 on day 28 reported high sensitivity and specificity to predict the risk of BPD (IGF-1: sensitivity: 89.29%, specificity: 77.78%, AUC: 0.8710; IL-18: sensitivity: 53.57%, specificity: 83.33%, AUC: 0.7887). And more substantial predictive power was found in combined analysis of IGF-1 and serum IL-18 on day 14: the sensitivity was 91.07% and the specificity was 83.33%, with the AUC of 0.9142.ConclusionIGF-1 and IL-18 might be closely involved in the occurrence and development of BPD. The serum concentration of IGF-1 combined with IL-18 could be potentially sensitive markers for the early diagnosis and severity of BPD.

P07-53 Identification of residues of organophosphorus and carbamate pesticides in serum samples of infants living in agricultural and fishing settings in Magangue, northern Colombia

P07-53 Identification of residues of organophosphorus and carbamate pesticides in serum samples of infants living in agricultural and fishing settings in Magangue, northern Colombia

Predicting Exposure to Perfluorinated Alkyl Substances (PFAS) among US Infants.

PFASs have been detected in nearly every serum sample collected over the last two decades from US adults as part of the National Health and Nutrition Examination Survey (NHANES) and are commonly found in other data sets from around the world. However, less is known about infant PFAS exposures, primarily because the collection of infant serum samples is less common and frequently avoided. Cord blood samples are often preferred for chemical exposure assessments because this is thought to provide a good representation of infant serum concentrations, at least at the time of birth. In this paper, we will provide a statistical and probabilistic analysis of what can be expected for infants living in the US using NHANES from 2007 to 2008, which contains a rare subset of infant data. Regulatory efforts that require estimation of exposures among the very youth can be challenging, both because of a lack of data in general and because variability among this most vulnerable population can be uncertain. We report that US infant exposures are extremely common and that serum concentrations remain fairly constant, despite infant growth rates and relatively high caloric and fluid intake, with the possible exception of PFOS. Infant serum PFOS concentrations between months 1 and 3 are consistently higher than at less than one month, even though healthy infants at 1 and 2 months weigh more than they did at birth. This suggests that the babies are exposed to greater concentrations of PFOS after birth or that excretion kinetics differ for this PFAS.

Assessing Environmental Enteric Dysfunction via Multiplex Assay and its Relation to Infant Growth Among HIV-Exposed Infants in Dar es Salaam, Tanzania

ObjectivesEnvironmental enteric dysfunction (EED), a subclinical state of intestinal inflammation, may contribute to poor growth in children in low-resource settings, but validated biomarkers are lacking. Multiplex assays, such as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), hold promise due to their ability to capture multiple domains of EED; however, MEEDAT’s ability to predict poor growth has not been well established. We sought to examine the relationship between markers of EED and growth among HIV-exposed infants in Dar es Salaam, Tanzania. MethodsWe performed a sub-study of 467 infants of HIV-infected mothers who participated in a randomized, double-blind, placebo-controlled trial assessing the effect of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks and 6 months were analyzed for anti-flagellin and anti-LPS IgA and IgG via ELISA as well as MEEDAT, which incorporates two markers of EED [fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Biomarkers were categorized into quartiles for primary analyses and as continuous exposures for exploratory analyses. Associations with subsequent growth outcomes [length-for-age Z-score (LAZ), weight-for-length Z-score (WLZ), and weight-for-age Z-score (WAZ)] at 12 months of age were assessed using linear regression. ResultsAt 12 months, nearly half (∼46%) of infants were stunted (LAZ <-2), and ∼3% were wasted (WLZ <-2). Higher concentrations of anti-LPS IgG at 6 months were significantly associated with lower LAZ at 12 months (ptrend = 0.034). In continuous analyses, higher concentrations of anti-flagellin IgA at 6 weeks were significantly associated with lower LAZ at 12 months (β: –0.46, 95% CI: –0.82, –0.11) as were anti-LPS IgA (β: –0.28, 95% CI: –0.53, –0.03) and anti-LPS IgG (β: –0.24, 95% CI: –0.48, –0.01) at 6 months. Higher concentrations of anti-flagellin IgA and anti-LPS IgA at 6 months were significantly associated with lower WAZ at 12 months (β: –0.34, 95% CI: –0.61, –0.07; β: –0.24, 95% CI: –0.44, –0.04). No significant associations were observed between I-FABP or sCD14 and infant growth at 12 months. ConclusionsUnlike anti-flagellin and anti-LPS Igs, MEEDAT’s biomarkers of EED, I-FABP and sCD14, were not associated with subsequent growth among HIV-exposed infants in Tanzania. Funding SourcesNIDDK and NICHD.

Determination of four bisphenol environmental hormone residues in infant serum by liquid chromatography-tandem mass spectrometry

Bisphenols are important industrial raw materials that are widely used to produce plastic bottles (feeding bottles), infant cups, and food and beverage (milk powder) cans. Because of the estrogen-like effect of bisphenols, even low-dose intake of these compounds by trace migration affects normal hormone levels in the human body. Therefore, it is imperative to develop a rapid, accurate, and highly sensitive method for the determination of bisphenols in serum. In this study, methyl tert-butyl ether (MTBE) was used as the extraction solvent, and the liquid-liquid extraction pretreatment method was used for sample processing. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for the simultaneous determination of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) at trace levels in infant serum. The important parameters affecting the extraction efficiency, such as the extraction solvent, extraction time, and extraction solvent volume for the four bisphenol environmental hormones were optimized. Serum samples were extracted by MTBE at 40℃ for 15 min. The target compounds were separated on a Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) using ultrapure water and methanol solution containing 0.5 mmol/L ammonium acetate as the mobile phases, with gradient elution at a flow rate of 0.2 mL/min. Finally, the analytes were analyzed by HPLC-MS/MS in the negative ion mode. BPA, BPB, and BPS showed good linearity in the range of 0.25-100 μg/L, while BPF showed good linearity in the range of 1-100 μg/L. The correlation coefficients were 0.9929-0.9959, and the limits of detection for BPA, BPB, BPS, and BPF were 0.05, 0.05, 0.05, 0.5 μg/L, respectively. At the three spiked levels (5, 20, 100 μg/L), the average recoveries of BPA, BPB, BPS, and BPF ranged from 84.56% to 104.43%, and the relative standard deviations were less than 10%. The proposed method was successfully applied to the determination of bisphenol contents in 150 infant serum samples. BPA was detected in most serum samples, and the detection rates in the serum of boys and girls were 90.67% and 89.33%, respectively. The detection rates of BPF in the serum of boys and girls were 6.67% and 1.33%, respectively; the corresponding values for BPS were 5.33% and 16.00%. BPB was not detected. The proposed method has the advantages of simple operation, good recovery, and high precision, and it is suitable for the simultaneous determination of the four bisphenol environmental hormones in infant serum.

Serum choline in extremely preterm infants declines with increasing parenteral nutrition

PurposeCholine is an essential nutrient for fetal and infant growth and development. Parenteral nutrition used in neonatal care lack free choline but contain small amounts of lipid-bound choline in the form of phosphatidylcholine (PC). Here, we examined the longitudinal development of serum free choline and metabolically related compounds betaine and methionine in extremely preterm infants and how the concentrations were affected by the proportion of parenteral fluids the infants received during the first 28 postnatal days (PNDs).MethodsThis prospective study included 87 infants born at gestational age (GA) < 28 weeks. Infant serum samples were collected PND 1, 7, 14, and 28, and at postmenstrual age (PMA) 32, 36, and 40 weeks. The serum concentrations of free choline, betaine, and methionine were determined by 1H NMR spectroscopy.ResultsThe median (25th–75th percentile) serum concentrations of free choline, betaine, and methionine were 33.7 (26.2–41.2), 71.2 (53.2–100.8), and 25.6 (16.4–35.3) µM, respectively, at PND 1. The choline concentration decreased rapidly between PND one and PND seven [18.4 (14.1–26.4) µM], and then increased over the next 90 days, though never reaching PND one levels. There was a negative correlation between a high intake of parenteral fluids and serum-free choline.ConclusionCirculating free choline in extremely preterm infants is negatively affected by the proportion of parenteral fluids administered.Trial registrationClinicalTrials.gov Identifier NCT02760472, April 29, 2016, retrospectively registered.

Immunogenicity of a combined schedule of trivalent oral and inactivated polio vaccines in South African infants

ABSTRACTBackground: South Africa transitioned from using live-attenuated trivalent oral polio vaccine (tOPV), to a combination of tOPV and inactivated polio vaccine (IPV) in April 2009. We evaluated the immunogenicity of the South African combined tOPV-IPV schedule versus the tOPV-only schedule in South African infants.Methods: Serum samples of HIV-unexposed infants were analysed retrospectively from two cohorts; infants enrolled from April 2005 through June 2006 and infants enrolled from December 2009 to April 2010. The primary vaccination series of the tOPV-only schedule included doses at birth, 6, 10 and 14 weeks, and the tOPV-IPV schedule included tOPV at birth and 6 weeks and IPV at 6, 10 and 14 weeks. Serum polio neutralising antibody titres to serotype-1, serotype-2 and serotype-3 were evaluated in infants at 18 weeks of age.Results: Infants who received the tOPV-IPV schedule had higher GMTs than infants who received tOPV-only for serotype-2 (9.63 vs. 8.80, P < 0.001) and serotype-3 (10.01 vs. 8.53, P < 0.001), as well as higher sero-protective titres for serotype-1 (100% vs. 96%, P = 0.014).Conclusion: Our data support the option of the South African combined polio vaccination schedule as an immunogenic option for a combined schedule.

Unique Pattern of N-Glycosylation, Sialylation, and Sulfonation on TSH Molecules in Serum of Children Up to 18 Months.

N-glycosylation and glycan composition of human TSH molecules modulate the biological properties of TSH in different physiological and clinical situations. The degree of sialylation of serum TSH was reported to be very low in normal third-trimester fetuses compared with normal adults. The circulating TSH glycoforms and their glycan compositions in young children have hitherto not been determined. To characterize N-glycosylation and glycan composition of circulating TSH molecules in young children. Serum samples were obtained from euthyroid individuals: 33 children, age 2 weeks to 3 years, and 264 adults. The di-glycosylated TSH and tri-glycosylated TSH glycoforms were determined and characterized with respect to sialylation and sulfonation. The TSH N-glycosylation was also examined in pituitary extracts of 75 individuals. In children up to 18 months of age, most TSH molecules were low-N-glycosylated, high-sulfonated, and low-sialylated compared with older children and adults. The degree of N-glycosylation was similar in serum and pituitary extracts up to 3 months of age and after that was higher in serum than in pituitary extracts. Children up to age 18 months had low-sialylated TSH molecules, similar to those reported for third-trimester fetuses. Most TSH molecules in young children were of smaller size and less negatively charged, favoring transport into their target tissues. The low sialylation favors a high biopotency at thyroid and extrathyroidal TSH receptors. A delayed development of the liver SO3-N-acetylgalactosamine receptor function after birth is a likely explanation of the highly sulfonated TSH molecules in serum samples of infants.

Gas chromatography-mass spectrometry based serum metabolic analysis for premature infants and the relationship with necrotizing enterocolitis: a cross-sectional study

BackgroundPreterm birth and feeding are the most important pathogenic factors of neonatal necrotizing enterocolitis (NEC). Metabonomic has been widely used in the diagnosis and treatment of other diseases, but there is no research on the related diseases of premature infants. Compared with full-term infants, the metabolism of preterm infants has its own specificity, so it can easily lead to NEC and other digestive tract inflammatory diseases. Metabonomic may be applied to the diagnosis of preterm related diseases, such as NEC.MethodsThe model was established with premature infant serum samples from 19 premature infants in our hospital, which was compared with the full-term infant control group. Serum was analyzed by gas chromatography-mass spectrometry (GC-MS), coupled with the analysis of serum metabolic characteristics. The variable important in projection, P value and Pearson correlation coefficient of samples were analyzed by using SIMCA, SPSS and other multivariate statistical analysis software.ResultsCompared to the term infants, premature infants had significantly higher levels of luteolin, and lower levels of xylose, O-succinyl-L-homoserine and lauric acid in the serum. There were some correlations among several different metabolites and clinically related indices (albumin, total bilirubin) for premature birth related diseases.ConclusionsThere are metabolic alterations in the serum of premature infants, which make contribution to the diagnosis of NEC.

Novel multiplex assay for profiling influenza antibodies in breast milk and serum of mother-infant pairs.

Background: During early life, systemic protection to influenza is passively provided by transplacental transfer of IgG antibodies and oral and gastrointestinal mucosal protection via breast milk (BM) containing predominantly IgA. Immune imprinting, influenced by initial exposure of the infant immune system to influenza, has recently been recognized as an important determinant of future influenza immune responses. Methods: We utilized stored frozen BM from a prospective birth cohort to assess immune factors in human milk. The earliest available BM and a paired, timed serum sample was assessed from each of 7 mothers. Paired infant serum samples were assayed at up to three time points during the first 12 months of life, one prior to assumed disappearance of transplacentally transferred IgG, and one after. We utilized a novel multiplex assay to assess mothers' and infants' IgG and IgA antibodies in serum to a panel of 30 individual recombinant hemagglutinin (rHA) proteins of influenza virus strains and chimeric rHAs. We also characterized IgA and IgG antibody levels in breast milk which provide mucosal protection. Results:Our pilot results, analyzing a small number of samples demonstrate the feasibility of this method for studying paired maternal-infant IgG and IgA anti-influenza immunity patterns. Unlike IgG antibodies, breast milk influenza virus HA-specific IgA antibody levels and patterns were mostly discordant compared to serum. As expected, there was a steady decay of infant influenza specific IgG levels by 6 to 8 months of age, which was not, however, comparable in all infants. In contrast, most of the infants showed an increase in IgA responses throughout the first year of life Conclusions: This new analytical method can be applied in a larger study to understand the impact of maternal imprinting on influenza immunity.

Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B.

BackgroundGlobally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy.Methodology/Principal findingsFrom 2013–2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups.Conclusions/SignificanceThese findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.

Novel multiplex assay for profiling influenza antibodies in breast milk and serum of mother-infant pairs

Background: During early life, systemic protection to influenza is passively provided by transplacental transfer of IgG antibodies and oral and gastrointestinal mucosal protection via breast milk (BM) containing predominantly IgA. Immune imprinting, influenced by initial exposure of the infant immune system to influenza, has recently been recognized as an important determinant of future influenza immune responses. Methods: We utilized stored frozen BM from a prospective birth cohort to assess immune factors in human milk. The earliest available BM and a paired, timed serum sample was assessed from each of 7 mothers. Paired infant serum samples were assayed at up to three time points during the first 12 months of life, one prior to assumed disappearance of transplacentally transferred IgG, and one after. We utilized a novel multiplex assay to assess mothers’ and infants’ IgG and IgA antibodies in serum to a panel of 30 individual recombinant hemagglutinin (rHA) proteins of influenza virus strains and chimeric rHAs. We also characterized IgA and IgG antibody levels in breast milk which provide mucosal protection. Results: Our pilot results, analyzing a small number of samples demonstrate the feasibility of this method for studying paired maternal-infant IgG and IgA anti-influenza immunity patterns. Unlike IgG antibodies, breast milk influenza virus HA-specific IgA antibody levels and patterns were mostly discordant compared to serum. As expected, there was a steady decay of infant influenza specific IgG levels by 6 to 8 months of age, which was not, however, comparable in all infants. In contrast, most of the infants showed an increase in IgA responses throughout the first year of life Conclusions: This new analytical method can be applied in a larger study to understand the impact of maternal imprinting on influenza immunity.

Novel multiplex assay for profiling influenza antibodies in breast milk and serum of mother-infant pairs.

Background: During early life, systemic protection to influenza is passively provided by transplacental transfer of IgG antibodies and oral and gastrointestinal mucosal protection via breast milk (BM) containing predominantly IgA. Immune imprinting, influenced by initial exposure of the infant immune system to influenza, has recently been recognized as an important determinant of future influenza immune responses. Methods: We utilized stored frozen BM from a prospective birth cohort to assess immune factors in human milk. The earliest available BM and a paired, timed serum sample was assessed from each of 7 mothers. Paired infant serum samples were assayed at up to three time points during the first 12 months of life, one prior to assumed disappearance of transplacentally transferred IgG, and one after. We utilized a novel multiplex assay to assess mothers' and infants' IgG and IgA antibodies in serum to a panel of 30 individual recombinant hemagglutinin (rHA) proteins of influenza virus strains and chimeric rHAs. We also characterized IgA and IgG antibody levels in breast milk providing mucosal protection. Results:Our pilot results, analyzing a small number of samples demonstrate the feasibility of this method for studying paired maternal-infant IgG and IgA anti-influenza immunity patterns. Unlike IgG antibodies, breast milk influenza virus HA-specific IgA antibody levels and patterns were mostly discordant compared to serum. As expected, there was a steady decay of infant influenza specific IgG levels by 6 to 8 months of age, which was not, however, comparable in all infants. In contrast, most of the infants showed an increase in IgA responses throughout the first year of life Conclusions: This new analytical method can be applied in a larger study to understand the impact of maternal imprinting on influenza immunity.

The impact of human breast milk components on the infant metabolism.

Background & aimsBreastfeeding is beneficial for mothers and infants. Underlying mechanisms and biochemical mediators thus need to be investigated to develop and support improved infant nutrition practices promoting the child health. We analysed the relation between maternal breast milk composition and infant metabolism.Methods196 pairs of mothers and infants from a European research project (PreventCD) were studied. Maternal milk samples collected at month 1 and month 4 after birth were analysed for macronutrient classes, hormone, and fatty acid (FA) content. Phospholipids, acylcarnitines, and amino acids were measured in serum samples of 4-month old infants. Associations between milk components and infant metabolites were analysed with spearman correlation and linear mixed effect models (LME). P-values were corrected for multiple testing (PLME).ResultsMonth 1 milk protein content was strongly associated with infant serum lyso-phosphatidylcholine (LPC) 14:0 (PLME = 0.009). Month 1 milk insulin was associated to infant acetylcarnitine (PLME = 0.01). There were no associations between milk protein content and serum amino acids and milk total fat content and serum polar lipids. Middle- and odd-chain FA% in breast milk at both ages were significantly related to serum LPC and sphingomyelins (SM) species in infant serum (all PLME<0.05), while FA% 20:5n-3 and 22:6n-3 percentages were significantly associated to serum LPC 22:6 (PLME = 1.91×10−4/7.93×10−5) in milk only at month 4. Other polyunsaturated fatty acids and hormones in milk showed only weak associations with infant serum metabolites.ConclusionsInfant serum LPC are influenced by breast milk FA composition and, intriguingly, milk protein content in early but not late lactation. LPC 14:0, previously found positively associated with obesity risk, was the serum metabolite which was the most strongly associated to milk protein content. Thus, LPC 14:0 might be a key metabolite not only reflecting milk protein intake in infants, but also relating high protein content in milk or infant formula to childhood obesity risk.