| ObjectiveGiven the benefits of folic acid(FA)supplement use in preventing the incidence of neural tube defects(NTDs),most countries have recommended women planning or capable of pregnancy to use FA,or have introduced mandatory FA fortification policy.With the widespread use of FA,its safety issues have gradually attracted attention.In recent years,the prevalence of complications during pregnancy has been increased year by year.Whether it is related to the use of FA is worth investigating.The objectives of this study are as follows:(1)To investigate the use of FA supplement among pregnant women in Wuhan,and to evaluate the status of FA supplement use among pregnant women.(2)To analyze the relationship between FA supplement use among pregnant women and the risk of gestational diabetes mellitus(GDM)with consideration of both doses and duration.(3)To explore the relationships between FA supplement use among pregnant women and the risk of gestational hypertension(GH)and pre-eclampsia(PE)with consideration of both doses and duration.MethodsThe participants came from the Tongji Maternal and Child Health Cohort(TMCHC).Information of socio-demiology,lifestyle,history of disease,family history of disease,history of drug use,nutritional supplement use,dietary intake and so on was collected through face-to-face questionnaires when they were included in the cohort within 16 weeks of gestation.The information of height,weight,blood pressure was also measured at enrollment.Information on lifestyle,nutritional supplement use,dietary intake,weight,and blood pressure of pregnant women was also collected during follow-up visits in the middle and late trimesters of pregnancy.Oral glucose tolerance test(OGTT)was performed from 24 to 28 weeks of gestation for GDM diagnosis.GDM is diagnosed according to criteria provided by the International Association of Diabetes and Pregnancy Study Groups(IADPSG).The diagnosis of GH was based on the measured BP ?130/80 mm Hg after 20 weeks of gestation;the diagnostic criteria for PE were GH with urine protein 2+ or urine protein >300 mg/24 h.Delivery and birth information was collected at delivery.(1)According to the information on FA supplement use,we investigate the FA supplement use status among pregnant women with consideration of both doses and duration.According to the doses and duration of FA supplement use,pregnant women were divided into 5 groups: Non-users(never use FA or doses <400 ?g/day or duration<4 weeks),short-term low-dose group(FA400-S,FA 400?800 ?g/day with short duration),long-term low-dose group(FA400-L,FA 400?800 ?g/day with long duration),short-term high-dose group(FA800-S,FA ?800 ?g/day with short duration)and long-term high-dose group(FA800-L,FA ?800 ?g/day with long duration).(2)Pregnant women with information on FA and GDM/OGTT diagnosis were included,and the relationship between the doses and duration of FA and GDM was analyzed.Logistic regression was used to analyze the relationship between FA supplement use and GDM risk.A linear regression model was used to analyze the relationship between FA supplement use and fasting blood glucose,1-hour postprandial blood glucose(1-h PBG)and 2-h PBG at OGTT.(3)Among pregnant women with information on FA and GH/PE diagnosis,the relationships of FA with GH and PE were investigated with consideration of both doses and duration.The relationship between FA supplement use and the risk of GH and PE were analyzed using robust Poisson regression.Results(1)A survey of 7635 pregnant women with reliable information on FA supplement use found that pregnant women in Wuhan used no FA supplement(8.0%,614/7635),used FA supplement with a daily dose <400 ?g/day(1.7%,131/7635),daily dose ?1000?g/day(2.6%,197/7635)and duration <4 weeks(3.7%,284/7635).Only 14.4%(1097/7635)of the pregnant women started taking FA at 12 weeks or earlier pre-pregnancy,10.8%(827/7635)of the pregnant women started taking FA at 4?12weeks pre-pregnancy,and most(66.8%,5097/7635)pregnant women started taking FA within 4 weeks pre-pregnancy or after pregnancy.Grouped the pregnant women into five groups according to the doses and duration of FA supplement use,there were 1025(13.4%)women in Non-users group;2811(36.8%)women in FA400-S group;878(11.5%)women in FA400-L group;2316(30.4%)women in FA800-S group and 605(7.9%)women in FA800-L group.(2)Of the 4353 pregnant women,8.4% of the participants were diagnosed with GDM.After adjusting for sociodemographic factors,lifestyle,family history,other supplements and weight gain during pregnancy,compared with Non-users,the ORs for group of FA400-S,FA400-L,FA800-S and FA800-L were 1.30 [0.86-1.95],1.32[0.81-2.15],1.21 [0.80-1.82] and 2.09 [1.30-3.36],respectively.Stratified analyses of weight gain at OGTT,family history of diabetes,and fetal sex,the associations between FA800-L and increased risk of GDM were significant in women with lower(?7.7 kg)(OR 95% CI,2.10 [1.09-4.06])and higher weight gain at OGTT(>7.7 kg)(OR 95% CI,2.01 [1.01-3.99]),without(OR 95%CI,1.78 [1.07-2.96])and with family history of diabetes(OR 95%CI,5.53 [1.24-24.78]),with female(OR 95%CI,2.09 [1.05-4.16])and male fetuses(OR 95%CI,2.11 [1.09-4.11]).The results of linear regression analysis showed that FA800-L was associated with higher 1-h PBG(? 95% CI,0.34 [0.14-0.54]mmol/L)and 2-h PBG(? 95% CI,0.21 [0.06-0.36] mmol/L).(3)Of the 4853 pregnant women,23.9% and 3.3% of them were diagnosed with GH and PE,respectively.After adjusting for demographic factors,lifestyle,family history,other supplements,weight gain during pregnancy and other variables,the results of robust Poisson regression found that FA800-L was associated with higher GH risk compared to Non-users(RR 95% CI,1.32 [1.06-1.64]).The women in FA400-S(RR 95% CI,1.04[0.88-1.24]),FA400-L(RR 95% CI,1.13 [0.92-1.39])and FA800-S(RR 95% CI,1.04[0.87-1.24])were not associated with GDM risk.No significant association was found between FA800-L and the risk of PE(RR 95% CI,1.45 [0.74-2.83]).The results of the sensitivity analyses showed that among women with normal weight before pregnancy(RR 95% CI,1.32 [1.01-1.72]),no family history of hypertension(RR 95% CI,1.36[1.05-1.76]),and without GDM(RR 95% CI,1.26 [1.00-1.59]),the association between FA800-L and increased GH risk was still significant.Conclusions(1)Among pregnant women in Wuhan,there are women of non-users,with insufficient or excessive dose,with irregular duration of FA supplement use,and who start taking FA too late.The current status of FA supplement use among pregnant women in Wuhan City needs to be improved,and the safety of irregular FA supplement use needs to be evaluated.(2)This study was the first large prospective cohort to report that high-dose(?800?g/day)FA supplement use from pre-pregnancy through mid-pregnancy was associated with an increased risk of GDM.(3)This study was the first to report that high-dose(?800 ?g/day)FA supplement use from pre-pregnancy through mid-pregnancy was associated with an increased risk of GH.Our findings suggest that high-dose(?800 ?g/day)FA supplement use from pre-pregnancy through mid-pregnancy should be avoided for general women planning or capable of pregnancy. |
PDF Full Text Request