Primary outcomes
Significant differences were noted in serum LDH levels of women diagnosed with preeclampsia compared to controls (Figure 2 ). Significant asymmetry was observed following assessment of the forest plot with the majority of assessed studies falling into the level of higher statistical significance (p<.01); thus, suggesting that it might be attributed to other reasons than publication bias. The trim and fill function included 11 simulated studies and the overall effect following their addition was not significant (MD -334.42, 95%CI -334.42, 58.81, p=.162 ). The meta-regression function did not reveal a significant effect of the NOS score and publication year on the outcomes of the meta-analysis. Trial sequential analysis revealed that the required sample size was reached to ensure the adequacy of findings. Prediction intervals did not reach statistical significance (-385.82, 744.45 IU/L).
Similarly, differences among mild preeclampsia cases and controls were also noted. Significant asymmetry was observed that was also attributed to other reasons than publication bias as the majority of studies fell into the level of high statistical significance (p<.01). The trim and fill function included 7 simulated studies and the overall effect following their addition was not significant (MD 68.85, 95%CI -22.75, 160.45). The meta-regression analysis revealed that the effect was significantly skewed by the parameters of NOS and publication year; thus, denoting that the asymmetry might be the result of these parameters. The required information was exceeded with the first fraction of studies as denoted by the trial sequential analysis results. Prediction intervals fell into the non-significant level (-101.47, 453.74).
Severe preeclampsia cases had more pronounced differences compared to control women (MD 371.86, 95% CI 258.76, 484.97 IU/L). Funnel plot analysis revealed significant asymmetry that was not attributed to publication bias. The trim and fill function included 7 simulated studies and the overall effect following their addition maintained statistical significance (MD 175.68, 95%CI 18.53, 332.83). Meta-regression analysis revealed that both the NOS and publication year influenced the results of the primary analysis; thus, denoting that the asymmetry might be the result of these factors. Sample size was adequate to support this finding.
Direct comparison of cases with mild with those that had severe preeclampsia revealed that women with mild preeclampsia had significantly lower levels of LDH (MD -162.04, 95% CI -217.18, -106.80 IU/L) (Figure 3 ). Ten simulated studies were added with the trim and fill function which resulted in non-significant differences among the two groups (MD -51.25, 95%CI -125.18, 22.67). As in the case of the previous comparisons, funnel plot analysis revealed that asymmetry was not attributed to publication bias, but meta-regression analysis failed to reveal a significant effect of the quality of included studies or of the year of publication to these findings. Sample size was adequate to support the result of the meta-analysis.