Tumor Necrosis Factor-α Allele Lymphotoxin-α+250 Is Associated with the Presence and Severity of Placental Inflammation among Preterm Births

Kazzi, S. Nadya J.; Jacques, Suzanne M.; Qureshi, Faisal; Quasney, Michael W.; Kim, U Olivia; Buhimschi, Irina

doi:10.1203/01.pdr.0000130474.12948.a4

Cited by 26 publications

(15 citation statements)

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“…22,23 There was a lack of association in our study (Table IV). Among very preterm infants, umbilical vein IL-6 has been shown to be elevated with both early neonatal sepsis and histologic chorioamnionitis, while TNF-α is not.…”

Section: Discussioncontrasting

confidence: 59%

Cord blood biomarkers of the fetal inflammatory response

Mestan

Thorsen

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

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In current neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age(GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR<5%, P<0.001) to account for multiple comparisons. Among 506 births (GA 23-42wks), IL-1β increased with FIR among preterm subgroups (P=0.0001 for <32wks; P=0.0009 for 33-36wks). IL-6 and IL-8 increased with FIR among preterm and full-term infants (P<0.0001). P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.

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Section: Discussioncontrasting

confidence: 59%

Cord blood biomarkers of the fetal inflammatory response

Mestan

Thorsen

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

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“…The high IL-6 (Ϫ174G) producing polymorphism indicated a significantly different distribution between African-American and Caucasian women and was associated with spontaneous PTD [27]. The association of TNF-␣ gene variants with clinical [28] or histologic chorioamnionitis [18] in two recent reports provided evidence for the relationship between inflammatory processes, cytokine genes, and adverse pregnancy outcomes. Conditioned on the maternal IFN-␥ genotype, the fetal high-producer IFN-␥ (ϩ874T) allele indicated a significant association with PTD in our study.…”

Section: Discussionmentioning

confidence: 97%

Role of Single Nucleotide Polymorphisms of Cytokine Genes in Spontaneous Preterm Delivery

et al. 2006

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“…interleukin-6 or 13), or deficiency in Toll-like receptor 4, which is a critical receptor component for gram-negative bacteria's lipopolysaccharide inflammatory response, show increased susceptibility to hyperoxia-induced lung injury. [19][20][21][22][23] In humans, polymorphisms in surfactant protein A & B, TNF-α, angiotensin-converting enzyme and gluthathione-S-transferase-P1 genes, genes, and having known altered biological functions, have been linked in small studies with variations in risk of BPD or its severity, [24][25][26][27] although others have failed to show similar associations in independent populations. 28,29 PDA persistence was also largely heritable in our analysis, a finding that is consistent with a significant contribution of individual's ethnic background to susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

2008

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Objective-The goal was to determine the magnitude of genetic effects on susceptibility and risk factors for bronchopulmonary dysplasia by using the clinically validated National Institutes of Health consensus definition as a demonstrated proxy for long-term respiratory and neurodevelopmental outcomes in extremely low birth weight infants.Methods-We analyzed clinical data from twin pairs born at ≤30 completed weeks gestation in British Columbia, Canada, between 1993 and 2006. Differences in correlations between monozygotic (MZ) and dizygotic (DZ) twin pairs and model-fitting approaches were used to quantify the relative contribution of genetic, shared environmental and non-shared environmental effects.Results-Among 318 twins of known zygosity, monozygotic twin pair similarities were greater than those observed for dizygotic pairs, which suggest significant heritability for bronchopulmonary dysplasia. Model-fitting analyses confirmed that genetic effects accounted for 82% and 79% of the observed variance in bronchopulmonary dysplasia susceptibility, defined on the basis of the need for supplemental oxygen at 36 weeks or the National Institutes of Health consensus definition, respectively. Variations in rates of hemodynamically significant PDA were largely accounted for by genetic effects, whereas variance in susceptibility to blood-borne bacterial infections was largely attributable environmental factors both common and unique to each infant.Conclusions-Susceptibility to BPD and persistence of PDA are both significantly heritable. Our study strengthens the case for investigating further genetic risk stratification markers useful for predicting the most significant long-term respiratory and neurodevelopmental consequences of bronchopulmonary dysplasia in premature neonates.

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Tumor Necrosis Factor-α Allele Lymphotoxin-α+250 Is Associated with the Presence and Severity of Placental Inflammation among Preterm Births

Cited by 26 publications

References 50 publications

Cord blood biomarkers of the fetal inflammatory response

Cord blood biomarkers of the fetal inflammatory response

Role of Single Nucleotide Polymorphisms of Cytokine Genes in Spontaneous Preterm Delivery

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

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