| Objective:To investigate the relationship between folate intake and risk of preeclampsia by source(supplement,diet)and types(folic acid only,folic acid-containing multivitamin,or combination)of folate intake during different time periods of pregnancy(before conception or during early pregnancy,before conception only,during early pregnancy only,before conception and during early pregnancy)and by preeclampsia subtypes(early or late onset,mild or severe).The results will provide scientific evidence to nutritional intervention on reducing the risk of preeclampsia and its subtypes.Methods:1.Pregnant women who delivered at the Department of Obstetrics,from the First Affiliated Hospital of Shanxi Medical University between March 2012 and September 2016 were recruited in the study,as the research object.A standardized questionnaire was administered by trained interviewers to collect information on demographics(age,family income,educational level,residence,etc);environmental and lifestyle factors;past history of hypertensive disorder complicating pregnancy in pregnant women or mother or sister,reproductive history;dietary and supplementary intake.Maternal complications during pregnancy and birth outcomes were abstracted from medical records.2.Adopting case-control study,by the questionnaire investigation,882 women of preeclampsia were treated as cases,while 8166 women without preeclampsia and other hypertensive disorder complicating pregnancy were treated as controls.Analysis respectively of the relationship between folate intake and risk of preeclampsia by source(folic acid supplementation by taking vitamins or mineral supplements,dietary folate intake)and type(folic acid only,folic acid-containing multivitamin,or combination)of folate intake during different time periods of pregnancy(before conception or during early pregnancy,before conception only,during early pregnancy only,before conception and during early pregnancy)and by preeclampsia subtypes(early or late onset,mild or severe).3.The questionnaire was entered using Epidata3.1 software,and the data were cleaned and analyzed by SAS 9.4 software.Univariate analysis were conducted to compare selected characteristics between cases and controls by chi-square test.Unconditional logistic regression was used to estimate the associations between folate and risk of preeclampsia adjusting for confounding variables.P<0.05 was considered as statistical significance.Results:1.General status of woman who had preeclampsia and different source method of folate intake1.1 General status of pregnant woman who had preeclampsiaThis study from March 2012 to September 2016,a total of 10320 pregnant women participated in the study.After the exclusion criteria,there were 9048 women who had singleton live birth,with complete questionnaire,including 882 women diagnosed with preeclampsia.Among them,early onset preeclampsia accounted for 153 cases,late onset preeclampsia accounted for 729 cases,mild preeclampsia accounted for 102 cases,780 cases of severe preeclampsia.Majority(59.07%)of the participants lived in the city,more than half of the participants(60.24%)had family income per capita at the middle level,38.75% of the women received education at high school,etc.1.2 Folic acid supplementation and different types by taking vitamins or mineral supplementsA total of 1073 women did not take folic acid supplements(11.86%).Among those who took folic acid supplements,348 took folic acid supplements before conception only(3.85%),3418 during early pregnancy only(37.78%),1752 before conception and during early pregnancy(19.36%);After stratified by type of supplements,342 took folic acid only supplements before conception only(3.78%),3279 took folic acid only supplements during early pregnancy only(36.24%),1623 took folic acid only supplements before conception and during early pregnancy(17.94%);4 took folic acid-containing multivitamin only supplements before conception only(0.04%),52 took folic acid-containing multivitamin only supplements during early pregnancy only(0.57%),27 took folic acid-containing multivitamin only before conception and during early pregnancy(0.30%);2 had folic acid only and folic acid-containing multivitamin supplements before conception only(0.02%),87 had folic acid only and folic acid-containing multivitamin supplements during early pregnancy only(0.96%),7 had folic acid only and folic acid-containing multivitamin supplements before conception and during early pregnancy(0.08%).1.3 General status of dietary folate intakeDietary folate intake one year before pregnancy(μg/day): Q1(<121.554):2291 cases(25.32%),Q2(121.554~159.724): 2250 cases(24.87%),Q3(159.724~213.313): 2256 cases(24.93%),and Q4(≥213.313):2251 cases(24.88%);Dietary folate intake during early pregnancy(μg/day): Q1(<126.232): 2291 cases(25.32%),Q2(126.232~165.063):2254 cases(24.91%),Q3(165.063~215.547):2241 cases(24.77%),and Q4(≥215.547):2262 cases(25.00%).2.Univariate analysis of the effect of folate intake on preeclampsia in pregnant womenUnivariate analysis of the preeclampsia showed that maternal age,family income,educational level,residence,previous pregnant women with hypertensive disorder complicating pregnancy history,gestational diabetes,pregnancy vomiting,passive smoking,parity,physical activity during pregnancy,pre-pregnancy body mass index,weight gain during pregnancy,childbirth season,folic acid supplementation,dietary energy intake were associated with preeclampsia,the differences all were statistically significant(P all<0.05).3.The relationship between different source method of folate intake and preeclampsia and its subtypes in different periods of pregnancy3.1 The relationship between folic acid supplementation and different types and preeclampsia and its subtypes in different periods of pregnancy3.1.1 The relationship between folic acid supplementation and preeclampsia in different periods of pregnancyAfter adjusting for maternal age,dietary folate intake,dietary total energy intake,compared with nonusers,folic acid supplementation before conception and during early pregnancy was a protective factor for preeclampsia(OR=0.667,95%CI: 0.503~0.885),no significant associations were observed between folic acid supplementation before conception or during early pregnancy(OR=0.907,95%CI: 0.734~1.121),before conception only(OR=1.172,95%CI:0.775~1.771),during early pregnancy only(OR=0.975,95%CI: 0.783~1.213).3.1.2 The relationship between folic acid supplementation and early onset and late onset preeclampsia in different periods of pregnancyAfter stratified by preeclampsia subtypes,folic acid supplementation before conception only was a risk factor for early onset preeclampsia(OR=2.570,95%CI:1.262~5.231),folic acid supplementation during other different time periods of pregnancy was not associated with early-onset preeclampsia;folic acid supplementation before conception and during early pregnancy was a protective factor for late onset preeclampsia(OR=0.595,95%CI:0.435~0.813),folic acid supplementation during other time periods of pregnancy was not associated with late onset preeclampsia.3.1.3 The relationship between folic acid supplementation and mild and severe preeclampsia in different periods of pregnancyFolic acid supplementation before conception and during early pregnancy was a protective factor for severe preeclampsia(OR=0.654,95%CI: 0.487~0.878),no significant associations were observed between other different periods of pregnancy with folic acid supplementation and mild and severe preeclampsia.3.1.4 The relationship between different types of folic acid supplementation and preeclampsia in different periods of pregnancyFurther stratification by types of supplements,folic acid only supplements before conception and during early pregnancy was a protective factor for preeclampsia(OR=0.668,95%CI:0.501~0.891);no significant associations were observed between different periods of pregnancy with folic acid-containing multivitamin,folic acid only and folic acidcontaining multivitamin supplementation and preeclampsia.3.1.5 The relationship between folic acid only and early onset and late onset preeclampsia in different periods of pregnancyFolic acid only before conception only was a risk factor for early onset preeclampsia(OR=2.584,95%CI: 1.269~5.260).Folic acid only before conception and during early pregnancy was a protective factor for late onset preeclampsia(OR=0.599,95%CI: 0.436~0.823).3.1.6 The relationship between folic acid only and mild and severe preeclampsia in different periods of pregnancyFolic acid only before conception and during early pregnancy was a protective factor for severe preeclampsia(OR=0.649,95%CI: 0.480~0.876).3.2 The relationship between dietary folate intake and preeclampsia and its subtypes in different periods of pregnancy3.2.1 The relationship between dietary folate intake and preeclampsia in different periods of pregnancyAfter adjusting the confounding factors of maternal age,folic acid supplementation,dietary total energy intake,no significant associations were observed between different levels of dietary folate intake and the risk of preeclampsia during one year before pregnancy,during early pregnancy.3.2.2 The relationship between dietary folate intake and preeclampsia subtypes in different periods of pregnancyAfter stratified by preeclampsia subtypes,,no significant associations were observed between different levels of dietary folate intake and early and late onset,mild and severe preeclampsia during a year before pregnancy,during early pregnancy.Conclusions:1.Folic acid supplementation before conception and during early pregnancy can reduce the risk of preeclampsia,and the protective effect was mainly seen for late onset and severe preeclampsia.Folic acid supplementation before conception only was a risk factor for early onset preeclampsia.2.Similar associations were observed for folic acid only supplements.No associations were found for folic acid-containing multivitamin supplementation.3.No significant associations were observed between dietary folate intake and the risk of preeclampsia and its subtypes. |
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