Cord Blood IgA Research Articles

Umbilical Cord Blood IgA Levels and Bacterial Profile in Preterm Neonates Born with Maternal Risk Factors for Early-Onset Neonatal Sepsis.

To investigate the IgA levels and bacterial profile in umbilical cord blood (UCB) samples of mothers with risk factors compared to those without risk factors; and to understand the link between UCB culture positivity and neonatal outcomes [early-onset sepsis (EOS) or death within 7 d of life]. This is a pilot prospective case-control study. Mothers with preterm deliveries (gestational age <34 wk) were enrolled in two groups- Cases: Those with antenatal risk factors (prolonged duration of rupture of membranes of ≥24h or chorioamnionitis) and controls: Those without these two risk factors. Serum IgA levels was assayed and microbiological culture was tested in UCB samples. 16S sequencing to determine the UCB microbiome was performed in a subset of samples (n = 15). Neonates were followed-up for the occurrence of EOS or death until 7 d of life. Forty-nine mothers as cases and 50 mothers as controls were consecutively enrolled. No significant difference was observed in the IgA levels (60.5 vs. 58.1mg/L; p = 0.71), neonatal blood culture positivity (4.1% vs. 8.0%; p = 0.41) and UCB culture positivity (30.6% vs. 26.0%; p = 0.61) in the two groups.No difference was observed between the groups in occurrence of EOS or death within 7 d of life. Proteobacteria, Firmicutes and Actinobacteria were the most abundant phyla. Serratia, Bifidobacterium, Collinsella, Meganomas and Blautia being the most common genera. Cord blood IgA concentration could not differentiate the neonates at-risk of infection due to its presence in both the groups.

Maternal diet during pregnancy and lactation and cow's milk allergy in offspring.

Diet during pregnancy and lactation may have a role in the development of allergic diseases. There are few human studies on the topic, especially focusing on food allergies. We sought to study the associations between maternal diet during pregnancy and lactation and cow's milk allergy (CMA) in offspring. A population-based birth cohort with human leukocyte antigen-conferred susceptibility to type 1 diabetes was recruited in Finland between 1997 and 2004 (n=6288). Maternal diet during pregnancy and lactation was assessed by a validated, 181-item semi-quantitative food frequency questionnaire. Register-based information on diagnosed CMA was obtained from the Social Insurance Institution and completed with parental reports. The associations between maternal food consumption and CMA were assessed using logistic regression, comparing the highest and the lowest quarters to the middle half of consumption. Consumption of milk products in the highest quarter during pregnancy was associated with a lower risk of CMA in offspring (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.37-0.86; P<0.01). When stratified by maternal allergic rhinitis and asthma, there was evidence of an inverse association between high use of milk products and CMA in offspring of non-allergic mothers (OR 0.30, 95% CI 0.13-0.69, P<0.001). Cord blood IgA correlated positively with the consumption of milk products during pregnancy, indicating exposure to CMA and activation of antigen-specific immunity in the infant during pregnancy. High maternal consumption of milk products during pregnancy may protect children from developing CMA, especially in offspring of non-allergic mothers.

Transfer of maternal IgE can be a common cause of increased IgE levels in cord blood

IgE in cord blood is thought to be a product of the fetus. A high level of total IgE is therefore used as a measure of atopic propensity in the newborn. We recently found strong evidence that allergen-specific IgE in cord blood was the result of transfer of maternal IgE to fetal blood or cord blood (maternofetal transfer) rather than fetal production. This also suggests that total IgE in cord blood might primarily be a maternal product. We sought to determine to what extent increased levels of total IgE in cord blood is the result of maternofetal transfer of IgE. Total IgE in cord blood was analyzed in a prospective birth cohort study. Maternofetal transfer of IgE was detected by means of high-sensitivity analyses of cord blood IgA and allergen-specific IgE and comparison with parental IgE levels and levels at 6 months of age. Forty-six percent of cord blood samples with increased IgE levels (>or=0.5 IU/mL) showed indication of maternofetal transfer of IgE. Maternal origin of IgE in these samples was validated by showing reduced levels of IgE at 6 months of age compared with samples with no indication of maternofetal transfer (geometric mean, 9.4 vs 5.4 IU/mL; P = .01). Maternofetal transfer was not appropriately accounted for by the conventional method of cord blood IgA measurement. Maternofetal transfer might be a common cause of increased cord blood IgE levels. Future studies should take potential maternofetal transfer into account or use other markers of atopy.

Sensitization Does Not Develop In Utero

Bønnelykke K, Pipper CB, Bisgaard H. J Allergy Clin Immunol. 2008;121(3):646–651 PURPOSE OF THE STUDY. To investigate the relationship of allergen-specific immunoglobulin E (IgE) in cord blood to sensitization in early infancy and the origin of such IgE. STUDY POPULATION. There were 243 children followed from birth. The patients were part of the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) and, thus, were considered to be at risk for atopy because of a maternal history of asthma. METHODS. Cord blood IgE was determined at the time of birth and again at 6 months of age. Total IgE, specific IgE to milk and egg, and a cumulative level of specific IgE to a panel of common aeroallergens were analyzed and compared with maternal IgE. Cord blood IgA was also assessed as a marker of maternal contamination of fetal blood, because IgA is not thought to cross the placental barrier during pregnancy. RESULTS. Specific IgE against mixed allergens was detected in 34 (14%) of the cord blood samples, and specific IgE against single allergens was detected in 22 samples. IgA was detected in 98% of the samples. None of the specific IgE found in cord blood was detected at 6 months of age. Cord blood IgE was not detected in any infants whose mothers were not sensitized, and the infants who did have cord blood IgE detected displayed a “fingerprint match” to maternal IgE. In every case, the IgE for a specific allergen detected in cord blood was the same as that detected in maternal blood, and it was present in a relatively similar concentration to that found in maternal blood. The cord blood IgA level also showed a linear relationship to the IgE level, suggesting that more maternal contamination resulted in higher IgE levels in cord blood. CONCLUSIONS. IgE in cord blood does not reflect in utero sensitization but seems to reflect maternofetal transfer of IgE. REVIEWER COMMENTS. The questions rarely change, but our answers often do. In recent years, the American Academy of Pediatrics recommended that some parents avoid certain foods during pregnancy to reduce the chance of their child developing atopic disease. These recommendations were based on studies that showed that the human fetus is capable of producing IgE as early as the 20th week of gestation and that cord blood IgE seemed to be a predictor of future atopy. Now the evidence seems to suggest that although sensitization could theoretically occur in utero, it simply does not. This study provides convincing evidence that the IgE in cord blood does not come from the infant but, rather, from the mixing of maternofetal blood, probably at the time of delivery. This study, along with other evidence that has come to light recently, raises questions about whether maternal dietary restriction of allergens during pregnancy impacts allergy outcomes to the avoided food/foods.

Sensitization does not develop in utero

Intrauterine sensitization has been suggested to play a role in the development of atopic disease in children, and this has led to current guidelines recommending allergen avoidance during pregnancy. To investigate the relevance of allergen-specific IgE in cord blood to sensitization in early infancy and the origin of such IgE. Inhalant and food allergen-specific IgE in cord blood was analyzed and compared with specific IgE in infant blood at 6 months of age and in parental blood. Cord blood IgA was measured to detect maternal blood contamination of cord blood. Allergen-specific IgE, primarily against inhalant allergens, was detected in 14% of cord blood samples. However, corresponding specific IgE was not found in infant blood at 6 months of age. Specific IgE in cord blood completely matched specific IgE in maternal blood with respect to allergen specificity, level of specific IgE, and ratio of total IgE/specific IgE. Finally, there was a correlation between specific IgE and IgA in cord blood. Allergen-specific IgE in cord blood does not reflect intrauterine sensitization but seems to be the result of transfer of maternal IgE to the fetus.

Diagnosis of congenital toxoplasmosis in the neonatal period: A multicenter evaluation

Objective: To evaluate different laboratory tests used to diagnose congenital toxoplasmosis in the neonatal period. Study design: A retrospective multicenter study of 294 pregnant women who experienced seroconversion for Toxoplasma gondii and subsequently delivered live-born infants. Fetal infection was assessed via specific IgM and IgA antibodies (cord and neonatal blood) and detection of T gondii in placenta and cord blood by mouse inoculation. Results: Ninety-three (32%) of the 294 infants were congenitally infected. The sensitivity of IgA in cord blood and in neonatal blood was 64% and 66%; the sensitivity of IgM was 41% and 42%, respectively. Mouse inoculation of the placenta and cord blood had sensitivities of 45% and 16%. Positive results of the serologic tests in congenitally infected children correlated significantly with the gestational age at the time of maternal infection but was not significantly influenced by the administration of specific antiparasitic treatment during pregnancy. Conclusion: Specific T gondii IgA antibody is a more sensitive test than IgM for detecting congenital toxoplasmosis in the neonatal period. The overall specificity is better for serologic tests performed on neonatal blood than for those on cord blood. Neonatal screening with IgM or IgA antibodies will not detect the majority of children with congenital toxoplasmosis when the maternal infection occurred before the 20th week of pregnancy. (J Pediatr 1999;135:714-9)

Evaluation of IgA measurements as a method for detecting maternal blood contamination of cord blood samples.

Several studies have evaluated the value of cord blood IgE concentrations for predicting the risk of allergic disease in children. In all of these studies it is necessary to exclude cord blood samples in which the IgE may be falsely elevated due to admixing of maternal and fetal blood during parturition. The most common method for detecting mixing of fetal and maternal blood is measurement of cord blood IgA concentrations. We have examined the theoretical basis of IgA measurements for detecting maternal blood contamination and reexamined our own data to evaluate IgA measurements. Our data suggest that the average IgA concentration of 28.2 micrograms/ml used in previous studies may not adequately exclude contaminated cord blood sample. Failure to reject contaminated cord blood samples would reduce the positive predictive value of cord blood IgE measurements.

Neonatal IgA and IgE levels among infants with paternal heredity for atopic disease

Serum IgA and IgE levels were studied in the postnatal period in 21 infants having a paternal heredity of atopic disease. Three different sampling techniques were used, aspirated cord blood (CB), gravity-collected cord blood, and capillary collected blood at 4-5 days of age. Significant differences among the three sampling techniques were recorded for IgA (P < 0.01), but not for IgE. The IgA levels decreased from birth to 4-5 days of age in 90% (19/21 of infants (P < 0.01). The corresponding decrease in IgE levels was 20%. This postnatal difference in the frequency of decreasing/increasing IgA and IgE levels was significant (P < 0.05). An analysis of CB IgA to detect maternal contamination of CB was found to be of questionable value, since only 50% (2/4) of the cases with an elevated CB-IgA level could be considered contaminated. The results of this study further emphasize that aspiration of CB and capillary collection of blood at 4-5 days of age are the best sampling techniques to avoid contamination. The general finding that paternal heredity had no significant influence on infant IgE contrasts with the strong influence of maternal heredity. Further studies will show whether the explanation lies in genetic or transplacental factors, or in both kinds of factors.

Cord blood IgE. I. IgE screening in 2814 newborn children.

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l were regarded as elevated. 13.2% of the sera contained at least 0.5 kU/l of IgE, with a significant preponderance in boys. Geometric mean cord blood IgE was 0.13 kU/l and 0.12 kU/l, respectively. Geometric mean cord blood IgE was significantly higher in boys. A significant seasonal variation with lowest IgE values in the autumn was found. No correlation between cord blood IgE and birth weight or gestational age was demonstrated. Only few newborns had cord blood IgA values greater than 0.014 g/l, calculated as geometric mean cord blood IgA + 2 SD among children with no detectable cord blood IgE, indicating infrequent contamination with maternal blood.

Serum immunoglobulins IgG, IgM, and IgA in maternal cord blood pairs from infants of normal and low birthweights in Tanzania.

Serum total protein, albumin, IgG, IgM, and IgA were determined in cord blood of 54 term infants appropriate-for-gestation-age (AGA), 14 preterm AGA infants, and 21 small-for-dates infants, and in their mothers immediately after delivery in Dar-es-Salaam. The mean serum levels of total protein, albumin, and IgG in mothers who delivered a term AGA infant were 6.8 g/100 ml, 2.9 g/100 ml, and 1840 mg/100 ml respectively, whereas those from their infants were 6.9 g/100 ml, 4.1 g/100 ml, and 1471 mg/100 ml. The de novo synthesis of IgM and IgA during fetal life seems to be activated at an earlier gestational age than in infants in Western countries; this fact subsequently resulted in a higher detection rate for IgM and IgA in cord blood of term AGA infants. IgG in Tanzanian mothers was generally higher than in corresponding cord blood sera, which is contrary to the finding in Europe.

IgD and the fetal immune response.

IgD was detected in 84% of cord sera at term by an inhibition-of-hemagglutination test, in contrast to low incidences reported earlier. Cord blood IgD and maternal serum IgD values were unrelated to each other, consistent with a fetal origin of the IgD. The cord blood IgD failed to correlate, either directly or inversely, with cord blood IgA or IgM, suggesting that its presence does not reflect fetal synthesis of specific antibody but rather may be developmental.

Fetal immune response following prematurely ruptured membranes

Concentrations of immunoglobulins (Ig)A1, and IgA2, IgD, IgE, IgG, and IgM have been determined in cord blood, amniotic fluid, and maternal serum in a group of patients with a history of prematurely ruptured membranes (PRM) prior to the onset of labor and in a control group of patients undergoing normal delivery and without a history of infection during pregnancy. IgA and IgD were determined by sensitive hemagglutination-inhibition tests; IgG and IgM, by radial immunodiffusion; IgE, by a radiommunoassay. There was evidence for an immune response in 10 of 16 cases of PRM: five of 16 had increased IgA but normal IgM; three of 16 had increased IgA and IgM; two of 16 had high IgM and normal IgA in cord blood. In patients with significantly increased levels of either IgA or IgM or both, there was a decreased level of IgD. These changes are most likely the result of the immune response to ascending infection from the maternal genitals. The sensitive testing method employed could demonstrate the presence of IgD in 53 per cent of normal cord blood samples and 72 per cent of amniotic fluid samples obtained at term. IgE was found in all normal cord blood and amniotic fluid samples tested. By concentrating the amniotic fluid up to 180-fold, IgM was demonstrated in all normal samples tested. The potential importance of IgA determinations in cord blood in addition to IgM determination for detection of intrauterine infections is stressed.