Enhanced NVP-BKM120 estrogen receptor activity is involved in the proinflammatory cascade leading to parturition. Furthermore, estrogen receptor activation facilitates labor by enhancing transcription of genes encoding uterine contraction-associated proteins including oxytocin and COX-2, which catalyzes the production of prostaglandins. Distinct functions associated with the studied gene group and network connectivity of predicted TFs are indicative of diverse etiology for PPROM and sPTB. A relatively small number of studies and genes was included in the analyses of PPROM, therefore, further work on PPROM is required using an unbiased genome wide approach to elucidate potential novel mechanisms. One of the weaknesses of this study is reliance on candidate gene association studies. Lack of GWAS studies specific to sPTB and pPROM results in biases in candidate gene selection. As many of the authors of candidate gene studies have been involved in infection/inflammation area of research, that pathway dominates in gene selection. However, the unbiased GWAS approaches such as the GENEVA GWAS study, failed to generate any genomewide significant results potentially because spontaneous PTB cases were analysed together with all indicated PTB cases. Future GWAS studies should eliminate the biases in candidate gene selection and examine further diverse etiology of sPTB and pPROM. In addition, gene-gene and gene-environment interactions cannot be assessed through IPA analysis. These, together with comorbidity such as coagulopathies and collagen disorders, and their interaction with inflammatory triggers that may produce discrete phenotypes, will have to be incorporated into clinical trial design and data collection of future studies. We did not control for methodological quality of included studies. It was evident that quality of data from different studies varied; while comprehensive information on a large number of markers was available for Chilean and African American groups, in Caucasians, only limited information was available from several small association studies often reporting a single gene analysis. Several authors did not report on quality control processes, and did not include information on genotype call frequency, validation cohorts or statistical power calculations. In addition, no formal genetic analysis has been conducted in these studies to test for population stratification. Future work should include unbiased whole genome approaches in large, phenotypically well characterized cohorts of women with PTB and controls matched for ancestry. It is well known that the culture-dependent methods are biased towards rapidly growing cosmopolitan fungi. Besides the physical competition for space, the growth of fastidious fungi is limited by the temperature and length of the incubation period, the composition of the medium and the aerobic conditions for recovery. Thus, the fungi recovered in culture in this study do not represent all culturable fungi at the WNS sites. Along similar lines, the success of the culture-independent method is conditional to the quality of DNA available for amplification and the universality of the primers used for the construction of clone.