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Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

ABSTRACT: Because of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup analysis by population strata to: (1) reduce the confounding effect of population structure, (2) increase sample size and statistical power, and (3) elucidate the association between rs1800975 and PTB.We reviewed all published papers for PTB phenotype and SNP rs1800795 genotype. Maternal genotype and fetal genotype were analyzed separately and the analyses were stratified by population. The PTB phenotype was defined as gestational age (GA) < 37 weeks, but results from earlier GA were selected when available. All studies were compared by genotype (CC versus CG+GG), based on functional studies.For the maternal genotype analysis, 1,165 PTBs and 3,830 term controls were evaluated. Populations were stratified into women of European descent (for whom the most data were available) and women of heterogeneous origin or admixed populations. All ancestry was self-reported. Women of European descent had a summary odds ratio (OR) of 0.68, (95% confidence interval (CI) 0.51 - 0.91), indicating that the CC genotype is protective against PTB. The result for non-European women was not statistically significant (OR 1.01, 95% CI 0.59 - 1.75). For the fetal genotype analysis, four studies were included; there was no significant association with PTB (OR 0.98, 95% CI 0.72 - 1.33). Sensitivity analysis showed that preterm premature rupture of membrane (PPROM) may be a confounding factor contributing to phenotype heterogeneity.IL6 SNP rs1800795 genotype CC is protective against PTB in women of European descent. It is not significant in other heterogeneous or admixed populations, or in fetal genotype analysis.Population structure is an important confounding factor that should be controlled for in studies of PTB.

SUBMITTER: Wu W

PROVIDER: S-EPMC3639799 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

Wu Wilfred W Clark Erin A S EA Stoddard Gregory J GJ Watkins W Scott WS Esplin M Sean MS Manuck Tracy A TA Xing Jinchuan J Varner Michael W MW Jorde Lynn B LB

BMC genetics 20130425

<h4>Background</h4>Because of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup anal ...[more]

PMID: 23617681

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Project description:The results from epidemiologic studies linking blood folate concentrations, folic acid supplementation, or dietary folate to the risk of preterm birth are inconsistent. In this study, we aimed to summarize the available evidence on these associations. A systematic search of the PubMed/MEDLINE, Google Scholar, Web of Science, and Cochrane Library databases up to October 20, 2018 was performed and reference lists of retrieved articles were screened. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the highest vs. the lowest levels of folate concentrations, folic acid supplementation, and dietary folate were calculated using random-effects models. Subgroup analyses and univariate meta-regression were performed to explore the sources of heterogeneity. Ten studies (six prospective cohort studies and four case-control studies) were included on folate concentrations, 13 cohort studies were included about folic acid supplementation, and 4 cohort studies were included regarding dietary folate intake. Higher maternal folate levels were associated with a 28% reduction in the risk of preterm birth (OR 0.72, 95% CI 0.56-0.93). Higher folic acid supplementation was associated with 10% lower risk of preterm birth (OR 0.90, 95% CI 0.85-0.95). In addition, a significant negative association was observed between dietary folate intake and the risk of preterm birth (OR 0.68, 95% CI 0.55-0.84), but no significant relation was seen between dietary folate and the risk of spontaneous preterm birth (OR 0.89, 95% CI 0.57-1.41). In the subgroup analysis, higher maternal folate levels in the third trimester were associated with a lower risk of preterm birth (OR 0.58, 95% CI 0.36-0.94). To initiate taking folic acid supplementation early before conception was adversely associated with preterm birth risk (OR 0.89, 95% CI 0.83-0.95). In conclusion, higher maternal folate levels and folic acid supplementation were significantly associated with a lower risk of preterm birth. The limited data currently available suggest that dietary folate is associated with a significantly decreased risk of preterm birth.

Project description:Despite remarkable progress in the reduction of under-five mortality, the rate of perinatal and neonatal mortality is still high especially in developing countries. The adverse outcome associated with preterm birth is one of the major public health challenges in Africa. However, there are limited and inconsistent studies conducted on the effect of preterm birth on adverse perinatal and neonatal outcomes in Ethiopia. Therefore, this systematic review and meta-analysis aimed to investigate the association between preterm birth and its adverse perinatal and neonatal outcomes in Ethiopia. We systematically searched several electronic databases like PubMed, Web of Science, SCOPUS, CINAHL, Google Scholar, African Journals Online databases and Science Direct. All identified observational studies were included. The I1 statistics were used to assess the heterogeneity among the studies. A random-effects model was computed to estimate the pooled effect of preterm birth on adverse perinatal and neonatal outcomes. Thirty-three studies with a total of 20 109 live births were included in the final meta-analysis. Our meta-analysis showed that preterm birth increased the odds of perinatal mortality by 10-folds [POR = 9.56 (95% CI: 5.47, 19.69)] and there was a 5.44-folds risk of stillbirth [Odds Ratio = 5.44 (95% CI: 3.57, 8.28)] among women who gave birth before 37 weeks of gestation. In addition, preterm birth was significantly associated with neonatal hypothermia [OR=3.54 (95% CI: 2.41, 5.21)], neonatal mortality [OR= 3.16 (95% CI: 1.57, 6.34). The sub-group analysis of this meta-analysis showed that there was an increased risk of neonatal sepsis [OR=2.33 (95% CI: 1.15, 4.71)] among preterm babies. Preterm births significantly increased the risk of adverse perinatal and neonatal outcomes in Ethiopia. Therefore, scale-up strategies and improving the quality of maternal and child health care providers should be an area of intervention to reduce adverse outcomes associated with preterm birth. The Federal Ministry of Health and concerned bodies should work towards the prevention of preterm birth and its adverse outcomes.

Dataset Information

Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

Publications

Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

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