| Objectives:A meta-analysis was performed to determine whether supplementation with vitamin C and/or E during pregnancy can reduces the risk of hypertensive disorders complicating pregnancy(HDCP) and other adverse maternal and perinatal outcomes, and to provide the theory evidence for the prevention of HDCP.Methods:All randomized controlled trials(RCTs) published on Embase, Pubmed, Scopus,Cochrane Central Register of Controlled Trials(CENTEAL), CNKI, Wanfang before March 10, 2016, were searched systematically using a combination of keywords and text words related to vitamin C or E, and HDCP. The reference lists of other systematic reviews and meta-analysis studies about these objectives were also searched. All English and Chinese eligible studies were included according to the inclusion criteria. And the valuable data information were extracted and analyzed by using the Review Manager software(Rev Man 5.3), with risk ratio(RR) as the effect of the factors, and 95% confidence interval(CI) representing each effect size range. If there is no heterogeneity(P<0.1 and I2≤50%), fixed-effect meta-analysis was used for combining data, and if statistical heterogeneity was detected(P≤0.1 or I2>50%), heterogeneous sources were investigated and random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were undertaken for primary outcomes based on the women’s risk status for HDCP. Finally, sensitivity analyses were undertaken to assess whether this made any difference to the overall result by exchanging the analyze method and expelling studies of high risk of bias or those lost to follow-up rate is greater than 10%.Results:Sixteen trials were included and all of them are RCTs, including thirteen literature in English and three literature in Chinese. Overall, 14 trials were judged to be of low risk of bias, and 2 trials of high risk of bias; 13 trials evaluated the combined effects of vitamin C and E supplementation(vit CE), and there are respectively 2 trials evaluated the effects of vitamin C or E supplementation alone. In 4 trials, the lost to follow-up rate is greater than10%, in 9 trials the rate is smaller than 10%, and the rate in other 3 trials are not clear.No significant difference was found between women supplemented with vit CE during pregnancy compared women in the control group for the risk of pre-eclampsia(RR=1.00;95%CI: 0.92-1.08; P=0.94; I2=15%), severe pre-eclampsia(RR=0.98; 95%CI: 0.83-1.17;P=0.86; I2=0%), eclampsia(RR=1.72; 95%CI: 0.82-3.62; P=0.15; I2=0%), HDCP(RR=1.01; 95%CI: 0.91-1.11; P=0.89; I2=64%), haemolysis elevated liver enzymes low platelets(HELLP) syndrome(RR=1.04; 95%CI, 0.58-1.86; P=0.90; I2=34%), maternal death(RR=1.35; 95%CI: 0.47-3.86; P=0.58; I2=0%), preterm birth(less than 37 weeks)(RR=0.94; 95%CI: 0.81-1.09; P=0.40; I2=42%), preterm birth(less than 32-34 weeks)(RR=0.98; 95%CI: 0.88-1.10; P=0.78; I2=30%), PROM(prelabour rupture of membranes)(RR=1.26; 95%CI: 0.92-1.73; P=0.15; I2=68%), perinatal death(RR=0.99;95%CI: 0.84-1.16; P=0.89; I2=18%), stillbirth(RR=1.23; 95%CI: 0.91-1.67; P=0.18;I2=2%), neonatal death(RR=0.76; 95%CI: 0.49-1.18; P=0.22; I2=0%), low birth weight(RR=1.01; 95%CI: 0.90-1.12; P=0.86; I2=41%), neonatal respiratory distress syndrome(RR=0.99; 95%CI: 0.89-1.10; P=0.85; I2=27%), neonatal assisted ventilation(RR=1.04;95%CI: 0.85-1.28; P=0.70; I2=27%), neonatal intensive care unit(NICU)(RR=1.01;95%CI: 0.94-1.09; P=0.74; I2=3%). Compared women in the control group, women supplemented with vitamin C and E compared at increased risk of having a gestational hypertension(RR=1.10; 95%CI: 1.05-1.17; P<0.001; I2=4%) and at decreased risk of placental abruption(RR=0.67; 95%CI: 0.46-0.98; P=0.08; I2=0%).After undertaking subgroup analyses for primary outcomes based on the women’s risk status for HDCP, significant difference was found between the women who supplemented vit CE and who did not in the subgroup of high risk of having HDCP and no differences were found in the subgroup analyses for outcomes of pre-eclampsia and HDCP.The sensitivity analysis outcome of HDCP and placental abruption between vit CE and control groups substantively change, and other outcomes did not change substantively to the prior analyses.No significant difference was found between women supplemented with vitamin C alone during pregnancy compared women in the control group for the risk of pre-eclampsia(RR=0.60; 95%CI: 033-1.07; P=0.08; I2=30%), severe pre-eclampsia(RR=0.76; 95%CI:0.27-2.19; P=0.61; I2=34%), low birth weight(RR=1.02; 95%CI: 0.74-1.37; P=0.92;I2=0%), preterm birth(RR=0. 87; 95%CI: 0.64-1.17; P=0.35; I2=0%).In this review, three trials assessed vitamin E supplementation alone in pregnancy;however, the data from these trials could not be used in the meta-analysis. Therefore, there was no available information to assess whether vitamin E supplementation alone can prevent HDCP.Conclusion:The pooled evidence in this meta-analysis does not support routine supplementation with vit CE can prevent HDCP. Conversely, supplementation with vit CE can increase the risk of gestational hypertension. So combined supplementation with vit CE is not recommended for the prevention of HDCP. And the effects of supplementation with vitamin C or E alone are not sure. But supplementation with vitimin C alone may has a positive effect on preventing HDCP. Further research is required to elucidate the possible role of vitamin C. |
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