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1.  Prenatal, perinatal, and heritable influences on cord blood immune responses 
Background
Maternal and perinatal environmental exposures, as well as inherited factors, may influence neonatal immune responses.
Objective
To determine relations of maternal and perinatal exposures to antigen-specific cord blood lymphoproliferative responses.
Methods
In 427 newborns from a Boston pregnancy/birth cohort, lymphoproliferative responses in cord blood mononuclear cells to stimulation with cockroach (Bla g 2), house dust mite (Der f 1), ovalbumin, and mitogen phytohemagglutinin were measured as stimulation index (SI). We used the Wilcoxon rank sum and χ2 tests to evaluate predictors of ovalbumin SI as a continuous ranked or dichotomous outcome. We used t test and Spearman correlation for univariate testing and linear regression to evaluate predictors of natural log-transformed Bla g 2, Der f 1, and phytohemagglutinin SI. Logistic multivariate regression was applied to evaluate predictors of Bla g 2, Der f 1, and phytohemagglutinin SI dichotomized at 2 or at the median for phytohemagglutinin.
Results
Maternal smoking during pregnancy, inadequate or excessive maternal weight gain during pregnancy, neonate black race/ethnicity (compared with white), and Apgar score less than 8 were each independently associated with increased cord blood mononuclear cell proliferative responses to stimulation with Bla g 2 and/or Der f 1. Maternal history of asthma was associated only with increased lymphoproliferative response to ovalbumin stimulation.
Conclusions
Distinct fetal and perinatal exposures and black race/ethnicity may be associated with increased cord blood lymphoproliferative responses. The implications of these findings for future development of allergy or asthma are, as yet, unknown.
PMCID: PMC1562525  PMID: 16597079
2.  Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-γ 
Background. N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been hypothesized to have opposing influences on neonatal immune responses that might influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development.
Objective. We evaluated whether cord blood fatty acid levels were related to neonatal immune responses and whether n-3 and n-6 PUFA responses differed.
Methods. We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n = 192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n = 191) and cytokine (IL-13 and IFN-γ; n = 167) secretion in a US birth cohort.
Results. Higher levels of n-6 linoleic acid were correlated with higher IL-13 levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P = .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced lymphocyte proliferation and IFN-γ levels in response to Bla g 2 and Der f 1 stimulation. Controlling for potential confounders, EPA and AA had similar independent effects on reduced allergen-stimulated IFN-γ levels. If neonates had either EPA or AA levels in the highest quartile, their Der f 1 IFN-γ levels were 90% lower (P = .0001) than those with both EPA and AA levels in the lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen-stimulated IFN-γ level.
Conclusion. Increased levels of fetal n-3 EPA and n-6 AA might have similar effects on attenuation of cord blood lymphocyte proliferation and IFN-γ secretion.
Clinical implications. The implications of these findings for
doi:10.1016/j.jaci.2005.12.1322
PMCID: PMC1508138  PMID: 16630954
Asthma; child; cord blood; cytokine; fatty acids; lymphocyte proliferation; AA: Arachidonic acid; BMI: Body mass index; CBMC: Cord blood mononuclear cell; CI: Confidence interval; DHA: Docosohexaenoic acid; EPA: Eicosapentaenoic acid; FA: Fatty acid; LA: Linoleic acid; NICU: Neonatal intensive care unit; OVA: Ovalbumin; PG: Prostaglandin; PUFA: Polyunsaturated fatty acid; SI: Stimulation index
3.  Cord Blood Cytokines and Acute Lower Respiratory Illnesses in the First Year of Life 
Pediatrics  2006;119(1):e171-e178.
OBJECTIVES
Little is known about the relation between cytokine profile at birth and acute lower respiratory illnesses in the first year of life. The purpose of this work was to examine the relation between cytokine secretions by cord blood mononuclear cells and acute lower respiratory illness in a birth cohort of 297 children.
METHODS
Cord blood mononuclear cells were isolated, and secretion of interferon-γ, interleukin-13, interleukin-10, and tumor necrosis factor-α at baseline and in response to allergens (Blatella germanica 2 and Dermatophagoides farinae 1) and mitogen (phytohemagglutinin) were quantified using enzyme-linked immunosorbent assay. Acute lower respiratory illness was defined as a parental report of a diagnosis of bronchiolitis, pneumonia, bronchitis, and/or croup by a health care professional in the first year of life. Differences in the levels of cord blood cytokines between children with and without acute lower respiratory illness were examined using 2-sample Wilcoxon tests. Logistic regression models were used to examine the relation between various categories of cord blood cytokines and acute lower respiratory illness.
RESULTS
Median levels of interferon-γ secreted by cord blood mononuclear cells in response to Blatella germanica 2 and Dermatophagoides farinae 1 were higher among children without acute lower respiratory illness as compared with children with acute lower respiratory illness. After adjustment for other covariates, the odds of acute lower respiratory illness was reduced among children in the top category (at or more than the median of detectable values) of interferon-γ level, significantly so in response to Blatella germanica 2.
CONCLUSIONS
In a cohort of children from the general population, we found that upregulated interferon-γ secretion at birth is associated with reduced risk of acute lower respiratory illness in the first year of life.
doi:10.1542/peds.2006-0524
PMCID: PMC1994927  PMID: 17145902
lower respiratory illnesses; cytokines; neonates; IFN-γ

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