Association between environmental dioxin-related toxicants exposure and adverse pregnancy outcome: systematic review and meta-analysis

Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity [I2] were used to evaluate heterogeneity. In either cohort studies [I2=0.89, p<0.0001] or case control studies [I2=0.69, p=0.02], significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure [RR=0.99, 95% CI:0.85-1.16], no significant increased risk of spontaneous abortion [SAB] with exposure to food dioxin-related compounds [RR=1.05, 95% CI:0.80-1.37], higher significant risks of low birth weight [LBW] with exposure to food dioxin-related compounds [RR=1.55, 95% CI:1.24-1.94], and higher significant risks of birth defects with maternal solid contaminants dioxin exposure [OR=1.24, 95% CI:1.19-1.29]. In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome

Association between maternal MTHFR polymorphisms and nonsyndromic cleft lip with or without cleft palate in offspring, a meta-analysis based on 15 case-control studies

The methylenetetrahydrofolate reductase [MTHFR] is thought to be involved in the development of nonsyndromic cleft lip with or without cleft palate [NSCL/P]. However, conflicting results have been obtained when evaluating the association between maternal MTHFR C677T and A1298C polymorphisms and the risk of NSCL/P. In light of this gap, a meta-analysis of all eligible case-control studies was conducted in the present study. A total of 15 case-control studies were ultimately identified after a comprehensive literature search and Hardy-Weinberg equilibrium [HWE] examination. Cochrane's Q test and index of heterogeneity [I[2]] indicated no obvious heterogeneity among studies. Fixed or random-effects models were used to calculate the pooled odds ratios [ORs]. The results showed that the TT genotype in mothers increased the likelihood of having NSCL/P offspring 1.25 times [95% CI: 1.047-1.494] more than the CC homozygotes. Meanwhile, maternal TT genotype increased the risk of producing NSCL/P offspring in recessive model [OR=1.325, 95% CI: 1.124-1.562]. However, the CT heterozygote and the CT+TT dominant models had no association with NSCL/P offspring compared with the CC wild-type homozygote model. Subgroup analyses based on ethnicity indicated that maternal TT genotype increased the likelihood of having NSCL/P offspring in Whites [OR=1.308, 95% CI: 1.059-1.617] and Asians [OR=1.726, 95% CI: 1.090-2.733] in recessive model. Also, subgroup analyses based on source of control showed that mothers with the 677TT genotype had a significantly increased susceptibility of having NSCL/P children in hospital based population [HB] when compared with CC homozygotes [OR=1.248, 95% CI: 1.024-1.520] and under the recessive model [OR=1.324, 95% CI: 1.104-1.588]. Furthermore, maternal A1298C polymorphism had no significant association with producing NSCL/P offspring [dominant model OR=0.952, 95% CI: 0.816-1.111, recessive model OR=0.766, 95% CI: 0.567-1.036]. MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor. MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring. However, further work should be performed to confirm these findings