Influence of maternal nutrition on outcome of pregnancy: prospective cohort study Antioxidants in the treatment of severe pre‐eclampsis an explanatory randomised controlled trial Optimal Glycemic Control, Pre-eclampsia, and Gestational Hypertension in Women With Type 1 Diabetes in the Diabetes and Pre-eclampsia Intervention Trial The effects of ascorbic acid, vitamin B6, vitamin B12, and folic acid supplementation on the breast milk and maternal nutritional status of low socioeconomic lactating women. Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial Regular vitamin C supplementation during pregnancy reduces hospitalization: outcomes of a Ugandan rural cohort study Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation Dietary protein energy supplementation of pregnant Asian mothers at Sorrento, Birmingham. II: Selective during third trimester only. The Role of Vitamin C in Prevention of Preterm Premature Rupture of Membranes The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension. Antioxidant activity, packed cell transfusions, and outcome in premature infants Iron supplementation in pregnancy: is less enough? The Diabetes and Pre-eclampsia Intervention Trial. A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour Vitamin C and E Supplementation to Prevent Spontaneous Preterm Birth: A Randomized Controlled Trial Vitamins C and E to prevent complications of pregnancy-associated hypertension. Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: a randomized placebo controlled clinical trial Fermented soyabean and vitamin C-rich fruit: a possibility to circumvent the further decrease of iron status among iron-deficient pregnant women in Indonesia. Effects of Ascorbic Acid on Serum Level of Unconjugated Estriol and Its Relationship with Preterm Premature Rupture of Membrane: A Double-Blind Randomized Controlled Clinical Trial Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation. Preterm labour--is bacterial vaginosis involved? Vitamins C and E in the latency period in women with preterm premature rupture of membranes. Impact of vaginal ascorbic acid on abnormal vaginal microflora Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function. An international trial of antioxidants in the prevention of preeclampsia (INTAPP). Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial. Drug use in pregnancy among Italian women Effects of maternal antioxidant supplementation on maternal and fetal antioxidant levels: a randomized, double-blind study. Does vitamin C and vitamin E supplementation prolong the latency period before delivery following the preterm premature rupture of membranes? A randomized controlled study. WHO sponsored collaborative studies on nutritional anaemia in India. The effect of parenteral iron administration in the control of anaemia of pregnancy. Vitamin C and E Supplementation Does Not Reduce the Risk of Superimposed PE in Pregnancy Studies of Nutrition in Pregnancy V: Ascorbic Acid Levels of Blood and Milk in Pregnancy and in Lactation Bacterial vaginosis diagnosed at the first antenatal visit better predicts preterm labour than diagnosis later in pregnancy Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis. Antenatal supplementation of antioxidant vitamins to reduce the oxidative stress at delivery--a pilot study. Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. PP170. Prenatal vitamin C and E supplementation is associated with a reduction in placental abruption and preterm birth in smokers.
Abstract Objective : To investigate the relations of maternal diet and smoking during pregnancy to placental and birth weights at term . Design : Prospect i ve cohort study . Setting : District general hospital in the south of Engl and . Participants : 693 pregnant nulliparous white women with singleton pregnancies who were selected from antenatal booking clinics with stratified r and om sampling . Main outcome measures : Birth and placental weights at term . Results : Placental and birth weights were unrelated to the intake of any macronutrient . Early in pregnancy , vitamin C was the only micronutrient independently associated with birth weight after adjustment for maternal height and smoking . Each ln mg increase in vitamin C was associated with a 50.8 g ( 95 % confidence interval 4.6 g to 97.0 g ) increase in birth weight . Vitamin C , vitamin E , and folate were each associated with placental weight after adjustment for maternal characteristics . In simultaneous regression , however , vitamin C was the only nutrient predictive of placental weight : each ln mg increase in vitamin C was associated with a 3.2 % ( 0.4 to 6.1 ) rise in placental weight . No nutrient late in pregnancy was associated with either placental or birth weight . Conclusions : Concern over the impact of maternal nutrition on the health of the infant has been premature Maternal nutrition , at least in industrialised population s , seems to have only a small effect on placental and birth weights . Other possible determinants of fetal and placental growth should be investigated . Key messages Placental and infant birth weights were not associated with the intake of any macronutrient early or later in pregnancy After adjustment for the effects of maternal height and smoking , only vitamin C independently predicted birth weight . The expected mean difference in birth weight for infants with mothers in the upper and lower thirds of intake was about 70 g Vitamin C was the only nutrient that independently predicted placental weight , but again this relation was of doubtful clinical significance Among relatively well nourished women in industrialised countries , maternal nutrition seems to have only a marginal impact on infant and placental size . Other causes of variation in the size of clinical ly normal infants should now be Objective To determine whether antioxidant therapy alters the disease process in severe early onset pre‐eclampsia , in support of the hypothesis that increased lipid peroxides and reactive oxygen species production play an important role in the pathogenesis of the disease OBJECTIVE To assess the relationship between glycemic control , pre-eclampsia , and gestational hypertension in women with type 1 diabetes . RESEARCH DESIGN AND METHODS Pregnancy outcome ( pre-eclampsia or gestational hypertension ) was assessed prospect ively in 749 women from the r and omized controlled Diabetes and Pre-eclampsia Intervention Trial ( DAPIT ) . HbA1c  ( A1C )  values were available up to 6 months before pregnancy ( n = 542 ) , at the first antenatal visit ( median 9 weeks ) ( n = 721 ) , at 26 weeks ’ gestation ( n = 592 ) , and at 34 weeks ’ gestation ( n = 519 ) and were categorized as optimal ( < 6.1 % : referent ) , good ( 6.1–6.9 % ) , moderate ( 7.0–7.9 % ) , and poor ( ≥8.0 % ) glycemic control , respectively . RESULTS Pre-eclampsia and gestational hypertension developed in 17 and 11 % of pregnancies , respectively . Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia ( P < 0.05 , respectively ) . In early pregnancy , A1C ≥8.0 % was associated with a significantly increased risk of pre-eclampsia ( odds ratio 3.68 [ 95 % CI 1.17–11.6 ] ) compared with optimal control . At 26 weeks ’ gestation , A1C values ≥6.1 % ( good : 2.09 [ 1.03–4.21 ] ; moderate : 3.20 [ 1.47–7.00 ] ; and poor : 3.81 [ 1.30–11.1 ] ) and at 34 weeks ’ gestation A1C values ≥7.0 % ( moderate : 3.27 [ 1.31–8.20 ] and poor : 8.01 [ 2.04–31.5 ] ) significantly increased the risk of pre-eclampsia compared with optimal control . The adjusted odds ratios for pre-eclampsia for each 1 % decrement in A1C before pregnancy , at the first antenatal visit , at 26 weeks ’ gestation , and at 34 weeks ’ gestation were 0.88 ( 0.75–1.03 ) , 0.75 ( 0.64–0.88 ) , 0.57 ( 0.42–0.78 ) , and 0.47 ( 0.31–0.70 ) , respectively . Glycemic control was not significantly associated with gestational hypertension . CONCLUSIONS Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy . These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes In this double-blind study , the effects of ascorbic acid , vitamin B6 , vitamin B12 , and folate supplementation on the maternal nutritional status and vitamin content of breast milk in 16 low socioeconomic lactating women were studied . Nine subjects were administered a commercial multivitamin-multimineral supplement and seven were given placebos . Milk sample s were collected four times per day at 4-h intervals from 5 to 7 and 43 to 45 days postpartum . Fasting blood sample s were taken from all mothers at the end of each milk collection period . Dietary records of all foods consumed were kept from 4 to 7 and 42 to 45 days postpartum . There were no significant differences in milk or plasma levels of ascorbic acid between the unsupplemented and supplemented groups . Both the EGPT index and milk concentration of vitamin B6 were significantly different ( p less than 0.01 ) between the unsupplemented and supplemented groups . The milk concentrations of vitamin B12 increased significantly ( p less than 0.05 ) in the supplemented group , as did the milk concentrations of folate ( p less than 0.01 ) . Because of consistently low levels of dietary vitamin B6 and folic acid in this group of low socioeconomic lactating women , either dietary changes or supplements could be necessary to maintain recommended levels of these vitamins in the womens ' breast milk BACKGROUND Vitamin C is involved in the synthesis and degradation of collagen and is important for maintenance of the chorioamniotic membranes . Inadequate availability of ascorbic acid during pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes ( PROM ) . OBJECTIVE The objective of the study was to evaluate the effectiveness of 100 mg vitamin C/d in preventing PROM . DESIGN A controlled double-blind trial was performed . Pregnant women ( n = 126 ) in their 20th wk of gestation were invited ; 120 accepted and were r and omly assigned to 2 groups  ( 100 mg vitamin C/d or placebo ) . Every 4 wk , plasma and leukocyte vitamin C concentrations were measured , and each subject was evaluated for cervicovaginal infection . The incidence of PROM was recorded for each group as an indicator of the protective effect of vitamin C supplementation . RESULTS One hundred nine patients finished the study .  Mean plasma vitamin C concentrations decreased significantly throughout the pregnancy in both groups ( P = 0.001 ) , and there were no significant differences between groups . Between weeks 20 and 36 , mean leukocyte vitamin C concentrations decreased from 17.5 to 15.23 microg/10(8 ) cells in the placebo group and increased from 17.26 to 22.17 microg/10(8 ) cells in the supplemented group ( within- and between-group differences : P = 0.001 ) . The incidence of PROM was 14 per 57 pregnancies ( 24.5 % ) in the placebo group and 4 per 52 pregnancies ( 7.69 % ) in the supplemented group ( relative risk : 0.26 ; 95 % CI : 0.078 , 0.837 ) . CONCLUSION Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens the incidence of PROM Summary Background Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia , but the effect in women with diabetes is unknown . We aim ed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes . Methods We enrolled women from 25 UK antenatal metabolic clinics in a multicentre r and omised placebo-controlled trial . Eligibility criteria were type 1 diabetes preceding pregnancy , presentation between 8 weeks ' and 22 weeks ' gestation , singleton pregnancy , and age 16 years or older . Women were r and omly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E ( α-tocopherol ) or matched placebo daily until delivery . The r and omisation sequence was stratified by centre with balanced blocks of eight patients . All trial personnel and participants were masked to treatment allocation . The primary endpoint was pre-eclampsia , which we defined as gestational hypertension with proteinuria . Analysis was by modified intention to treat . This study is registered , IS RCT N27214045 . Findings Between April , 2003 , and June , 2008 , 762 women were r and omly allocated to treatment groups ( 379 vitamin supplementation , 383 placebo ) . The primary endpoint was assessed for 375 women allocated to receive vitamins , and 374 allocated to placebo . Rates of pre-eclampsia did not differ between vitamin ( 15 % , n=57 ) and placebo ( 19 % , 70 ) groups ( risk ratio 0·81 , 95 % CI 0·59–1·12 ) . No adverse maternal or neonatal outcomes were reported . Interpretation Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes . However , the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing . Funding The Wellcome Trust Background Vitamin C or ascorbic acid is a hydro-soluble lactone ( synthesized from glucose ) essential to human body and available from diet . Despite its broad availability in fruits and vegetables , in many developing countries the incidence of clinical symptoms due to the vitamin deficiency is still very high . Also , pregnant women in the developing countries are frequently hospitalized for several preventable reasons such as anemia in pregnancy , mostly iron-deficient anemia ( IDA ) and the upper/lower respiratory tract infections ( RTI ) . The aim of the study was to investigate , in a Ug and an rural pregnant women cohort , the preventive effects of vitamin C supplementation on hospital admission . Methods 384 pregnant women met the inclusion criteria and were r and omly assigned to receive either 400 mg of vitamin C daily ( 187 ) or not ( 197 ) in addition to their st and ard antenatal vitamins until delivery . The primary outcome measure of this study was to assess the prevention of hospitalization during pregnancy in the group of women supplemented with vitamin C compared to the controls . Fisher‘s exact test was employed in this assessment . Results 42.2 % women in the vitamin C group and 27.9 % in the control group were not hospitalized during pregnancy ; this difference was found statistically significant . Conclusion The results of this study suggest including vitamin C in the guidelines of multivitamin prevention for pregnant women , especially in developing countries where seasonal availability of fruits and vegetables could result in adverse clinical outcomes Background Prenatal antioxidant supplementation might influence fetal lung growth and development and reduce infant respiratory morbidity . The aim of this study was to test the hypothesis that infants of mothers at risk of pre-eclampsia who were r and omised to receive high-dose vitamins C and E ( 1000 mg vitamin C and 400 IU RRR α-tocopherol daily ) during pregnancy would have better respiratory outcomes than infants whose mothers were r and omised to receive placebo . Methods Respiratory outcomes to 2 years of age were documented using question naires and , in a subset , by recording their healthcare utilisation and calculating the cost of care data . Results 330 women who had taken vitamin supplementation and 313 who had taken placebo completed the respiratory question naire ( 386 and 366 infants , respectively ) . There were no significant differences between the two groups in the proportions diagnosed with asthma . 54 women who had taken vitamin supplementation and 45 who had taken placebo  took part in the healthcare utilisation study ( 65 and 53 infants , respectively ) . On average , infants of mothers receiving vitamin supplementation had 2.6 ( 99 % CI 0.8 to 5.1 ) times more A&E/outpatient visits and 3.2 ( 99 % CI 0.2 to 6.9 ) times more GP visits than infants of mothers receiving placebo , and their costs of care were £ 226 ( 99 % CI £ 27 to £ 488 ) more for outpatient admissions , £ 57 ( 99 % CI £ 3 to £ 123 ) more for GP visits and £ 22 ( 99 % CI £ 3 to £ 50 ) more for medications . Conclusions High-dose antenatal vitamin C and E supplementation  does not improve infant respiratory outcome and is associated with increased healthcare utilisation and cost of care Unselective dietary protein energy supplementation of Asian mothers at Sorrento Maternity Hospital did not enhance intrauterine growth . The effect of selective supplementation was therefore studied . Forty-five mothers who at 28 weeks were known to be nutritionally at risk ( triceps increment less than or equal to 20 microns/week between 18 and 28 weeks ) received one of three supplements during the third trimester : ( a ) vitamins only -- a multivitamin sachet daily containing vitamins A , B , C , and D ; ( b ) energy--42 - 125 MJ ( 10 000 - 30 000 kcal ) , all from carbohydrate , plus vitamins ; ( c ) protein energy -- energy and vitamins as before , but with 5 - 10 % of energy from milk protein .  Eighty-three mothers regarded as adequately nourished at 28 weeks also received one of the three supplements . In the nutritionally at-risk mothers the protein energy supplement was associated with a heavier crude birth weight and heavier weight for gestational age .  Supplementation did not lead to improved intrauterine growth in those mothers who were adequately nourished . The differential effect of supplementation depending on the mothers ' nutritional state during the second trimester may explain apparently conflicting results of other studies where some have shown a substantial effect of supplementation and others only a small effect . This effect of intervention is further evidence that " poor nutrition " contributes to poor intrauterine growth in selected mothers , even in developed countries Background Preterm premature rupture of membranes ( PPROM ) is one of the most important complications of the pregnancy and cause perinatal morbidity and mortality . History of PPROM is a risk factor of recurrent PPROM . Vitamin C plays an important role in collagen metabolism and increases resistance maintenance of the chorioamniotic membranes . Objectives The aim of this study is to evaluate the role of vitamin C supplementation in prevention of PPROM in women with a positive history of PPROM . Patients and Methods This clinical trial study was performed on 170 pregnant women with the history of PPROM , with singleton pregnancy and gestational age 14 weeks in Imam-Reza Hospital , Mashhad University of Medical Sciences during 2008 to 2010 . They were r and omly divided into two groups . The case patients received 100 mg vitamin C daily from 14th weeks of gestation . PPROM occurrence was compared between two groups as an indicator of the protective effect of vitamin C supplements . Results PPROM occurred in 44.7 % of controls and 31.8 % of cases ( P < 0.05 ) . PROM occurred in 34.1 % of controls and 18.8 % of cases ( P < 0.05 ) . Pregnancy was terminated at term gestation in 21.2 % of controls and 49.4 % of cases ( P < 0.05 ) . Rupture of membranes was significantly decreased in the case group . Conclusions Vitamin C supplementations after 14th weeks of gestation can prevent from PPROM in women with the history of PPROM OBJECTIVE We sought to compare the rates of superimposed preeclampsia and adverse outcomes in women with chronic hypertension with or without prior preeclampsia . STUDY DESIGN We conducted secondary analysis of 369 women with chronic hypertension ( 104 with prior preeclampsia ) enrolled at 12 - 19 weeks as part of a multisite trial of antioxidants  to prevent preeclampsia ( no reduction was found ) . Outcome measures were rates of superimposed preeclampsia and other adverse perinatal outcomes . RESULTS Prepregnancy body mass index , blood pressure , and smoking status at enrollment were similar between groups . The rates of superimposed preeclampsia ( 17.3 % vs 17.7 % ) , abruptio placentae ( 1.0 % vs 3.1 % ) , perinatal death ( 6.7 % vs 8.7 % ) , and small for gestational age ( 18.4 % vs 14.3 % ) were similar between groups , but preterm delivery < 37 weeks was higher in the prior preeclampsia group ( 36.9 % vs 27.1 % ; adjusted risk ratio , 1.46 ; 95 % confidence interval , 1.05 - 2.03 ; P = .032 ) . CONCLUSION In women with chronic hypertension , a history of preeclampsia does not increase the rate of superimposed preeclampsia , but is associated with an increased rate of delivery at < 37 weeks AIM To evaluate the relative importance of biochemical markers of antioxidant status , gestational age , and parameters of neonatal care in the clinical outcome of premature infants . METHOD A prospect i ve , observational , longitudinal study of the association between these factors was conducted . Blood was collected from an in situ arterial line within two hours of birth and at intervals thereafter , when blood was drawn for routine clinical purpose s. Outcome was assessed as death , or survival with or without bronchopulmonary dysplasia ( BPD ) .  One hundred and forty four babies of 22 to 39 weeks of gestation , who required intensive care at the Jessop Hospital for Women , between January 1993 and April 1994 , were recruited . RESULTS Low gestational age at birth was the most important predictor of mortality and the development of BPD . Having corrected for gestational age , low plasma antioxidant activity at birth was an independent risk factor for mortality . Plasma vitamin C at birth was significantly higher in the babies who died compared with those with a good outcome , but this effect was not sustained after correcting for gestational age . Repeated measures of Analysis of Variance revealed a postnatal increase in antioxidant activity , caeruloplasmin , retinol , cholesterol corrected α tocopherol , and red blood cell superoxide dismutase ( SOD ) activity . Vitamin C , on the other h and , declined in all groups after birth . Logistic regression analysis revealed that the greater the number of packed cell transfusions received during intensive care , and the higher the concentration of vitamin C on the second day of life , the greater the risk of developing BPD . CONCLUSIONS After correcting for the effect of gestational age , low plasma antioxidant activity at birth was an independent risk factor for mortality . Frequent blood cell transfusions over the first week of life are associated with an increased risk of developing BPD . This association may be causal Background . The purpose of the present study was to evaluate the efficacy of low dose iron supplementation with and without a heme component , prescribed for women in the second half of pregnancy OBJECTIVE Rates of  pre-eclampsia  in women with type 1 diabetes are two to four times higher than in normal pregnancies . Diabetes is associated with antioxidant depletion and increased free radical production , and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia . The Diabetes and Pre-eclampsia Intervention Trial ( DAPIT ) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment . METHODS DAPIT is a r and omised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years . Women are r and omised to daily vitamin C ( 1000 mg ) and vitamin E ( 400 IU ) or placebo at 8 - 22 weeks of gestation until delivery . Maternal venous blood is obtained at r and omisation , 26 and 34 weeks , for markers of endothelial activation and oxidative stress and to assess glycaemic control . The primary outcome of DAPIT is pre-eclampsia . Secondary outcomes include endothelial activation ( PAI-1/PAI-2 ) and birthweight centile In a previous study from this institution , patients at high risk for preterm labour were screened for the presence of bacterial vaginosis ( BV ) . When BV was present , they were r and omised to receive either treatment ( metronidazole ) or placebo ( vitamin C ) . There were significantly more patients with preterm labour in the metronidazole group . The aim of this double-blind r and omised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour .  Patients with a history of preterm labour in a preceding pregnancy were r and omised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks ' gestation . They attended a dedicated premature labour clinic . Significantly more women delivered before term in the group that received vitamin C , but there was no difference in the outcome of the babies between the two groups . Supplementation with vitamin C did not prevent premature labour OBJECTIVE : To estimate whether maternally administered vitamins C and E lower the risk of spontaneous preterm birth . METHODS : This is a secondary analysis of a r and omized , double-masked , placebo-controlled trial in nulliparous women at low-risk administered 1,000 mg vitamin C and 400 international units vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery . Outcomes include preterm birth attributable to premature rupture of membranes ( PROM ) and total spontaneous preterm births ( spontaneous preterm birth attributable to PROM or spontaneous labor ) . RESULTS : Of the 10,154 women r and omized , outcome data were available for 9,968 ( 4,992 vitamin group and 4,976 placebo group ) . A total of 1,038 women ( 10.4 % ) delivered preterm , of whom 698 ( 7.0 % ) had  spontaneous preterm birth . A spontaneous preterm birth occurred in 356 women ( 7.1 % ) assigned to daily vitamin C and E supplementation and in 342 ( 6.9 % ) assigned to placebo . There were 253 women ( 2.5 % ) who delivered after preterm PROM and 445 ( 4.5 % ) after a spontaneous preterm labor . In women supplemented with vitamins C and E , births attributed to preterm PROM were similar at less than 37 and 35 weeks of gestation , but births were less frequent before 32 weeks of gestation ( 0.3 % compared with 0.6 % , adjusted odds ratio 0.3–0.9 ) . However , total spontaneous preterm births across gestation in women supplemented with vitamins C and E or a placebo were similar . CONCLUSION : Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00135707 . LEVEL OF EVIDENCE : BACKGROUND Oxidative stress has been proposed as a mechanism linking the poor placental perfusion characteristic of preeclampsia with the clinical manifestations of the disorder . We assessed the effects of antioxidant supplementation with vitamins C and E , initiated early in pregnancy , on the risk of serious adverse maternal , fetal , and neonatal outcomes related to pregnancy-associated hypertension . METHODS We conducted a multicenter , r and omized , double-blind trial involving nulliparous women who were at low risk for preeclampsia . Women were r and omly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the 9th and 16th weeks of pregnancy . The primary outcome was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels , thrombocytopenia , elevated serum creatinine levels , eclamptic seizure , medically indicated preterm birth , fetal-growth restriction , or perinatal death . RESULTS A total of 10,154 women underwent r and omization . The two groups were similar with respect to baseline characteristics and adherence to the study drug . Outcome data were available for 9969 women . There was no significant difference between the vitamin and placebo groups in the rates of the primary outcome ( 6.1 % and 5.7 % , respectively ; relative risk in the vitamin group , 1.07 ; 95 % confidence interval [ CI ] , 0.91 to 1.25 ) or in the rates of preeclampsia ( 7.2 % and 6.7 % , respectively ; relative risk , 1.07 ; 95 % CI , 0.93 to 1.24 ) . Rates of adverse perinatal outcomes did not differ significantly between the groups . CONCLUSIONS Vitamin C and E supplementation initiated in the 9th to 16th week of pregnancy in an unselected cohort of low-risk , nulliparous women did not reduce the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension ( Clinical Trials.gov number , NCT00135707 ) Haptoglobin ’s ( Hp ) antioxidant and pro-angiogenic properties differ between the 1 - 1 , 2 - 1 , and 2 - 2 phenotypes . Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant population s. We previously demonstrated that  preeclampsia  risk was doubled in white Hp 2 - 1 women , compared to Hp 1 - 1 women . Our objectives were to determine whether we could reproduce this finding in a larger cohort , and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension ( PAH ) . This is a secondary analysis of a r and omized controlled trial in which 10,154 low-risk women received daily vitamin C and E , or placebo , from 9 - 16 weeks gestation until delivery . Hp phenotype was determined in the study prediction cohort ( n = 2,393 ) and a case-control cohort ( 703 cases , 1,406 controls ) . The primary outcome was severe PAH , or mild or severe PAH with elevated liver enzymes , elevated serum creatinine , thrombocytopenia , eclampsia , fetal growth restriction , medically indicated preterm birth or perinatal death . Preeclampsia was a secondary outcome . Odds ratios were estimated by logistic regression . Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome . There was no relationship between Hp phenotype and the primary outcome or  preeclampsia in Hispanic , white/other or black women .  Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype . Supplementation increased preeclampsia risk ( odds ratio 3.30 ; 95 % confidence interval 1.61–6.82 , p<0.01 ) in Hispanic Hp 2 - 2 women . Hp phenotype does not influence preeclampsia risk , or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia Background Oxidative stress plays a role in the pathogenesis of pre-eclampsia . Supplementing women with antioxidants during pregnancy may reduce oxidative stress and thereby prevent or delay the onset pre-eclampsia . The objective of this study was to evaluate the effect of supplementing vitamin C in pregnancy on the incidence of pre-eclampsia , at Mulago hospital , Kampala , Ug and a. Methods This was a ( parallel , balanced r and omization , 1:1 ) placebo r and omized controlled trial conducted at Mulago hospital , Department of Obstetrics and Gynecology . Participants included in this study were pregnant women aged 15 - 42 years , who lived 15 km or less from the hospital with gestational ages between 12 - 22 weeks . The women were r and omized to take 1000 mg of vitamin C ( as ascorbic acid ) or a placebo daily until they delivered . The primary outcome was pre-eclamsia . Secondary outcomes were : severe pre-eclampsia , gestational hypertension , preterm delivery , low birth weight and still birth delivery .  Participants were 932 pregnant women r and omized into one of the two treatment arms in a ratio of 1:1 . The participants , the care providers and those assessing the outcomes were blinded to the study allocation . Results Of the 932 women recruited ; 466 were r and omized to the vitamin and 466 to the placebo group . Recruitment of participants was from November 2011 to June 2012 and follow up was up to January 2013 . Outcome data was available 415 women in the vitamin group and 418 women in the placebo group . There were no differences in vitamin and placebo groups in the incidence of pre-eclampsia ( 3.1 % versus 4.1 % ; RR 0.77 ; 95 % CI : 0.37 - 1.56 ) , severe pre-eclampsia ( 1.2 % versus 1.0 % ; RR 1.25 ; 95 % CI : 0.34 - 4.65 ) , gestational hypertension(7.7 % versus 11.5 % ; RR 0.67 ; 95 % CI : 0.43 - 1.03 ) , preterm delivery ( 11.3 % versus 12.2 % ; RR 0.92 ; 95 % CI : 0.63 - 1.34 ) , low birth weight ( 11.1 % versus 10.3 % ; RR 1.07 ; 95 % CI : 0.72 - 1.59 ) and still birth delivery ( 4.6 % versus 4.5 % ; RR 1.01 ; 95 % CI : 0.54 - 1.87 ) . Conclusions Supplementation with vitamin C did not reduce the incidence of pre-eclampsia nor did it reduce the adverse maternal or neonatal outcomes . We do not recommend the use of vitamin C in pregnancy to prevent pre-eclampsia . Trial registration This study was registered at the Pan African Clinical Trial Registry , PACTR201210000418271 on 25th October 2012 OBJECTIVE Increasing the consumption of Fe-rich foods and thus improving Fe bioavailability without significantly increasing diet cost is the most sustainable intervention for improving Fe intake . We assessed the effect of supplementary food consisting of fermented soyabean ( tempeh ) and vitamin C-rich fruit consumed during pregnancy on  maternal iron deficiency ( ID ) . DESIGN Pregnant women were r and omly allocated by village into optimized diet and control groups . Supplementary food was given 6 d/week at home . The average weekly food provided comprised 600 g of tempeh , 30 g of meat , 350 g of guava , 300 g of papaya and 100 g of orange .  Hb , ferritin and transferrin receptor ( TfR ) concentrations were measured at 12 - 20 and at 32 - 36 weeks of gestation . SETTING Thirty-nine villages in Indonesia . SUBJECTS Pregnant women ( 12 - 20 weeks of gestation , n 252 ) . RESULTS At baseline , mean Hb , ferritin and TfR concentrations and body Fe concentration were within the normal range and did not differ between groups . At near term , mean Hb , ferritin and body Fe decreased , whereas mean TfR increased significantly in both groups . The mean changes in Fe status were similar in both groups . In Fe-deficient women , consumption of an optimized diet was associated with smaller decreases in Hb ( 1·02 ( 95 % CI 0·98 , 1·07 ) g/l ; P = 0·058 ) , ferritin ( 1·42 ( 95 % CI 1·16 , 1·75 ) μg/l ; P = 0·046 ) and body Fe ( 2·57 ( 95 % CI 1·71 , 3·43 ) mg/kg ; P = 0·073 ) concentrations , compared with a state of no intervention . Fe-deficient women at baseline benefited more from supplementary food compared with Fe-replete women . CONCLUSIONS Daily supplementary food containing tempeh and vitamin C-rich fruits during pregnancy might have positive effects on maternal ID Background : Vitamin C is a water-soluble antioxidant that not only stimulates and protects collagen synthesis but also plays an important role in maintaining cellular integrity in a normal pregnancy . This study surveyed the effects of ascorbic acid on the serum level of unconjugated estriol and the relationship between unconjugated estriol and preterm premature rupture of membrane ( PPROM ) . Methods : This double-blind , r and omized clinical trial recruited 60 patients with predisposing factors to PPROM . The women were r and omly divided into two groups of intervention and control and received vitamin C and placebo , respectively . The intervention group received 250 mg vitamin C twice a day and the controls received the placebo only .  Unconjugated estriol was measured using the  ELISA .  All data were extracted and recorded in a checklist and compared using descriptive statistics as well as the x2 , Fisher exact , and t tests . Results : The demographic data showed no difference between the two groups . The mean level of serum unconjugated estriol was significantly lower in the intervention group than in the control group ( P=0.044 ) . Also , the frequency of PPROM was lower in the intervention group , but the difference was not significant ( P>0.05 ) . Unconjugated estriol levels were not significantly different between the healthy women and the PPROM patients . Conclusion : This study demonstrated that vitamin C administration decreased unconjugated estriol levels in the patients with PPROM . The findings of this study also indicated that administration of ascorbic acid was a safe and effective method to reduce the incidence of PPROM . Alteration in unconjugated estriol is an active mediator for this effect AIM To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α ( p38-MAPKα ) , Extra Cellular-Signal Regulated Kinase ( ERK ) and c-Jun NH2-Terminal Kinase ( JNK ) activity , in the pathogenesis of type 1 diabetic pre-eclampsia , and the putative modulation of these indices by maternal vitamin C and E supplementation . METHODS Placental sample s were obtained from a sub-cohort of the DAPIT trial : a r and omised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy . Placenta from placebo-treated : normotensive ( NT ) [ n=17 ] , gestational hypertension ( GH ) [ n=7 ] and pre-eclampsia ( PE ) [ n=6 ] and vitamin-treated : NT ( n=20 ) , GH ( n=4 ) and PE ( n=3 ) was analysed . Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue . Catalytic activities of placental p38-MAPKα , ERK and JNK were measured by enzyme-linked immunosorbent assay ( ELISA ) . RESULTS Nitrotyrosine immunostaining was present in placebo-treated NT , GH and PE placentae , with no significant difference observed between the groups . There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae . ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity . CONCLUSION Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy , possibly due to inherent oxidative stress and peroxynitrite production . Our results suggest that p38-MAPKα , ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation OBJECTIVE To assess the efficacy of treatment of bacterial vaginosis ( BV ) using metronidazole to reduce preterm labour in primigravidae and multigravidae with previous midtrimester abortion or preterm labour . DESIGN R and omised controlled trial . SETTING Tertiary academic hospital . METHOD Two different groups of patients were screened for BV at the first antenatal visit , namely primigravidae and high-risk multigravidae who had had a previous midtrimester abortion or preterm delivery . Patients where BV was diagnosed clinical ly or on Gram 's stain of a smear taken from the posterior vaginal fornix , received either 400 mg metronidazole , or 100 mg vitamin C orally twice daily for 2 days . The Gram 's stain was repeated after 4 weeks . If BV was found again , treatment with the same drug was repeated . OUTCOME MEASURES Preterm delivery , birth weight and perinatal deaths . RESULTS One thous and and five patients entered the study , but 40 were excluded for various reasons and 10 were lost to follow-up . There were 464 primigravidae , of whom 150 ( 32 % ) had BV . Except for the 5-minute Apgar score , no significant differences were found between primigravidae negative for BV and those who received either metronidazole or vitamin C. There were 491 high-risk multigravidae , of whom 127 ( 26 % ) had BV . The mean gestational age in the BV-negative group was 37 weeks , in contrast to 37.4 weeks in the vitamin C group and 35.6 weeks in the metronidazole group . Birth weights in these three groups were 2,752 g , 2,759 g and 2,475 g respectively , significantly less ( P = 0.0109 ) in the metronidazole group in comparison with the BV-negative group . Delivery before 37 weeks occurred in 29 % of high-risk multigravidae with no BV but in 24 % of those who took vitamin C and in 43 % who took metronidazole . Differences were significant between the BV-negative and metronidazole groups ( P = 0.0231 ) and also between the metronidazole and vitamin C groups ( P = 0.0274 ) . Delivery before 28 weeks occurred in 4 % of the high-risk multigravidae with no BV but in 10 % of those with BV who took metronidazole . The difference was significant ( P = 0.0430 ) . Analysis for maximum likelihood estimates for preterm labour identified only previous preterm labour or midtrimester abortion as risk factors . CONCLUSION Metronidazole does not seem to reduce the prevalence of preterm labour when given for BV before 26 weeks ' gestation OBJECTIVE To determine whether supplementation with vitamins C and E  after preterm premature rupture of membranes ( PPROM ) is associated with an increased latency period . METHODS In this double-blind , r and omized , controlled trial , 60 women with singleton pregnancies of 26 to 34 weeks ' duration and PPROM were r and omly assigned to vitamin C ( 500 mg/day ) and vitamin E ( 400 IU/day ) or placebo until delivery . All women received 2 doses of betamethasone in the first 24 h after admission as well as broad-spectrum antibiotic prophylaxis . RESULTS Important demographic , as well as clinical characteristics such as number of cases of chorioamnionitis , early neonatal sepsis , and respiratory distress syndrome , were similar in the 2 groups . A statically significant difference in the mean+/-S.D. number of days of latency was found between the groups ( 10.5+/-5.2 days vs. 3.5+/-4.0 days ( P = 0.03 ) . CONCLUSION Vitamins C and E supplementation of after PPROM is associated with a longer latency before delivery Purpose To evaluate the impact of vaginal ascorbic acid ( vitamin C ) as a treatment/maintenance regimen on increased vaginal pH and abnormal microflora on wet mounts in premenopausal women . Methods A r and omized study of 140 asymptomatic , low-risk pregnant and non-pregnant premenopausal women with vaginal pH ≥ 4.5 and a variety of partly/completely disrupted Lactobacillus microflora patterns on wet mounts in five outpatient clinics was carried out . Participants were r and omized to the intervention group [ 250 mg vitamin C tablets vaginally at bedtime once a day for 6 days ( treatment phase ) , followed by a one tablet per week , for 12 weeks ( maintenance phase ) ] or the control group ( no treatment ) . Outcomes were evaluated 4 months after r and omizing , i.e. , 2–3 weeks after the last vitamin C tablet insertion . Results Normalization to normal flora was observed in 51.4 % of all ascorbic acid and in 24.3 % of control group patients ( difference 27.1 % , 95 % CI 11.7–42.6 , p < 0.05 , ITT population ) . In the per protocol population , normalization was confirmed in 53.5 % of the intervention and 22.4 % of the control group ( difference 31 % , 95 % CI 14.3–47.8 , p < 0.05 ) . Results of pregnant subgroup analysis showed better outcomes for the subgroup : difference of normalization rate between ascorbic acid and control group was 41.2 % ( 95 % CI 21.8–60.1 , p < 0.05 ) . Itching occurred in 19 % ; 23 % of women reported irritation and 10 % stopped the treatment because of side effects . Conclusions Vaginal ascorbic  acid improves abnormal vaginal pH and microflora , especially in pregnant women , but is not well tolerated by all women BACKGROUND Oxidative stress could play a part in pre-eclampsia , and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder . Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors . METHODS We did a r and omised , placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals . We assigned the women 1000 mg vitamin C and 400 IU vitamin E ( RRR alpha tocopherol ; n=1199 ) or matched placebo ( n=1205 ) daily from the second trimester of pregnancy until delivery . Our primary endpoint was pre-eclampsia , and our main secondary endpoints were low birthweight ( < 2.5 kg ) and small size for gestational age ( < 5th customised birthweight centile ) . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 62368611 . FINDINGS Of 2404 patients treated , we analysed 2395 ( 99.6 % ) . The incidence of pre-eclampsia was similar in treatment placebo groups ( 15 % [ n=181 ] vs 16 % [ n=187 ] , RR 0.97 [ 95 % CI 0.80 - 1.17 ] ) . More low birthweight babies were born to women who took antioxidants than to controls ( 28 % [ n=387 ] vs 24 % [ n=335 ] , 1.15 [ 1.02 - 1.30 ] ) , but small size for gestational age did not differ between groups ( 21 % [ n=294 ] vs 19 % [ n=259 ] , 1.12 [ 0.96 - 1.31 ] ) . INTERPRETATION Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk , but does increase the rate of babies born with a low birthweight . As such , use of these high-dose antioxidants is not justified in pregnancy OBJECTIVE We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C ( 1000 mg/d ) and vitamin E ( 400 IU/d ) supplements . In this study , we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia . STUDY DESIGN Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously . RESULTS Indices of oxidative stress and placental function were abnormal in the placebo group . When the placebo group was compared with the women who were at low risk , ascorbic acid , plasminogen activator inhibitor-2 , and placenta growth factor concentrations were decreased ; and 8-epi-prostagl and in F(2alpha),leptin , and the plasminogen activator inhibitor-1/-2 ratio were increased . In the group that received vitamin supplements , ascorbic acid , 8-epi-prostagl and in F(2alpha ) , leptin , and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk . CONCLUSION Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease OBJECTIVE We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension ( GH ) and its adverse conditions among high- and low-risk women . STUDY DESIGN In a multicenter r and omized controlled trial , women were stratified by the risk status and assigned to daily treatment ( 1 g vitamin C and 400 IU vitamin E ) or placebo . The primary outcome was GH and its adverse conditions . RESULTS Of the 2647 women r and omized , 2363 were included in the analysis . There was no difference in the risk of GH and its adverse conditions between groups ( relative risk , 0.99 ; 95 % confidence interval , 0.78 - 1.26 ) . However , vitamins C and E increased the risk of fetal loss or perinatal death ( nonprespecified ) as well as preterm prelabor rupture of membranes . CONCLUSION Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH , but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes OBJECTIVE We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women . STUDY DESIGN Women at risk for preeclampsia ( previous preeclampsia , chronic hypertension , pregestational diabetes , or multifetal gestation ) were recruited at 14 to 20 weeks ' gestation and r and omly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins . The primary outcome was the occurrence of preeclampsia . An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50 % reduction in the rate of preeclampsia . RESULTS Funding was terminated after 109 women had been recruited ; 9 were lost to follow-up or withdrew . We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies . The rate of preeclampsia was not different : 17.3 % in women who received supplemental vitamins C and E , versus 18.8 % in the placebo group . Assuming a baseline rate of preeclampsia in the placebo group between 15 % and 20 % , we can estimate that 500 to 950 women in each arm will be required to show a clinical ly important reduction in the rate of preeclampsia . CONCLUSION The potential benefit of vitamin C and E supplementation to prevent  preeclampsia in women with clinical risk factors is smaller than we estimated . Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm Abstract Objective : To describe the use of drugs among Italian women during pregnancy and to compare it with other reports in Italy from the last 10 years . Methods : A r and om sample of women who delivered in 1995–1996 were interviewed with regard to the care they received during pregnancy , delivery and the post-natal period . Information on antenatal care included maternal reports on the use of drugs during pregnancy . Results : Of the 9004 women interviewed , 75 % took at least one drug during pregnancy . Users took a median number of two drugs . Iron ( 51 % ) and vitamins ( 25 % ) dominate prescriptions throughout pregnancy . Fifteen percent of women reported treatment for threatened abortion and 27 % for risk of pre-term delivery . The data do not differ from the drug exposure profile during pregnancy reported in other Italian studies . Logistic regression analysis of drug use ( excluding haematologicals and nutritionals ) shows an increased risk of usage for older women , the better educated , for those who reported health problems and those who had compulsory bed rest and /or hospitalisation during pregnancy . Conclusion : Seventy-five percent of the women reported use of at least one drug during pregnancy . Haematological and nutritional drugs are over prescribed . Although hormones have been clearly proven to be ineffective in preventing threatened abortion , the study shows an almost unchanged and out of date prescription pattern of progestational drugs . In order to avoid unnecessary exposure to potential risk , maternity care procedures should be review ed and strictly related to an “ evidence -based ” approach OBJECTIVE We sought to determine whether vitamins C and E could be delivered to the fetal-placental unit through maternal oral supplementation . STUDY DESIGN In a r and omized , double-blind study , 20 women received a daily prenatal vitamin with or without 400 IU of vitamin E and 500 mg of vitamin C , starting at 35 weeks ' gestation . At r and omization , a nutritional question naire , plasma vitamin C and E and  red blood cell ( RBC ) vitamin E levels were determined . At delivery , concentrations of maternal and fetal plasma vitamin C and E , maternal and fetal RBC vitamin E , amniotic fluid vitamin C , and chorioamnion vitamin E and tensile strength were determined . RESULTS Maternal plasma vitamin E levels increased in the supplemented women but not in the control subjects . No changes in maternal vitamin C levels were noted . Maternal plasma vitamin C concentrations at delivery correlated closely with amniotic fluid vitamin C levels . Similarly , maternal plasma vitamin E levels at delivery correlated with the chorioamnion concentration of vitamin E. CONCLUSIONS Maternal plasma vitamin E levels are increased by oral supplementation . Maternal plasma vitamin C and E concentrations correlate with the concentration of vitamin C in the amniotic fluid and vitamin E in the chorioamnion , respectively OBJECTIVE To determine whether maternal vitamin C and vitamin E supplementation after the premature rupture of membranes is associated with an increase in the latency period before delivery . METHODS In the present prospect i ve open r and omized trial , 229 pregnant women with preterm premature rupture of membranes ( PPROM ) at ≥ 24.0 and < 34.0 weeks ' gestation were r and omly assigned to receive either 1,000 mg of vitamin C and 400 IU of vitamin E ( n = 126 ) or a placebo ( n = 123 ) . The primary outcome was the latency period until delivery . Analysis was performed on an intention-to-treat basis . RESULTS No significant differences in demographic or clinical characteristics were observed between the groups . Latency period until delivery was significantly higher in the group that received vitamins compared with the control group ( 11.2 ± 6.3 days versus 6.2 ± 4.0 days ; p < 0.001 ) . Gestational age at delivery was also significantly higher in the vitamin group compared with the control group ( 31.9 ± 2.6 weeks versus 31.0 ± 2.6 weeks ; p = 0.01 ) . No significant differences in adverse maternal outcome ( i.e. , chorioamnionitis or endometritis ) or neonatal outcome ( i.e. , neonatal sepsis , neonatal death , necrotizing enterocolitis , or grade 3 to 4 intraventricular hemorrhage ) were noted between groups . CONCLUSIONS The findings of the present study suggest that the use of vitamins C and E in women with PPROM is associated with a longer latency period before delivery . Moreover , adverse neonatal and maternal outcomes , which are often associated with prolonged latency periods , were similar between the groups 1 . The relative efficacy of oral and parenteral iron administration in the prophylaxis and treatment of Fe-deficiency anaemia of pregnancy has been studied . 2 . Intravenous administration of Fe by total dose infusion of Fe dextran was not superior to oral Fe 120 mg/d , 6 d/week for 10 - 12 weeks . 3 . Intramuscular Fe dextran , 100 mg twice per week for 10 - 12 weeks , produced a significantly greater rise in mean haemoglobin concentration than oral Fe therapy . 4 . The superiority of intramuscular Fe as compared with intravenous Fe is probably related to the different h and ling of the Fe dextran by the reticulo-endothelial system . 5 . In spite of the better response to intramuscular Fe dextran , it is not recommended for public health practice because of the risks associated with its use and the much higher cost of the preparation and its delivery Background . Oxidative stress could play a role in the development of preeclampsia . There is some evidence to suggest that vitamin C and E supplements can reduce the risk of the disorder . We hypothesized its beneficial role in a group of pregnant women with essential hypertension . Methods . In this r and omized controlled trial , we enrolled 50 pregnant women with essential hypertension . We assigned the women 1000 mg vitamin C and 400 IU natural vitamin E ( RRR α tocopherol ; n = 25 ) , daily from the second trimester of pregnancy until delivery or no supplementation ( n = 25 ) . Our primary endpoint was development of superimposed preeclampsia , and main secondary endpoints were aggravation of hypertension , need for admission , need to increase antihypertensive drugs , and small size for gestational age ( < fifth customized birthweight centile ) . Results . We analyzed 50 women who completed the study .  The incidence of superimposed preeclampsia was similar in vitamin and control groups ( 8 % [ n = 2 ] vs 12 % [ n = 3 ] , p = 1.000 ) . Vitamin C and E supplementation also did not prevent aggravation of hypertension in group of women who took it ( 12 % [ n = 3 ] vs 32 % [ n = 8 ] , p = 0.172 ) . Small size for gestational age babies did not differ between groups ( 4 % [ n = 2 ] vs 6 % [ n = 3 ] , p = 1.000 ) . Conclusion . Vitamin C and E supplementation does not prevent development of superimposed preeclampsia in women with essential hypertension . Our results did not show any significant benefit of vitamin supplementation . There was some trend in lessening of hypertensive complications of pregnancy . Our results failed to find any correlation between development of superimposed preeclampsia and oxidative stress 1 The mean daily As . A. intakes of subjects in the second trimester , third trimester and at 6 weeks post partum were 81 , 72 and 77 mg . , respectively . 2 Weak correlations were found between As . A. intakes and whole blood , plasma and blood cells levels at all times . 3 Those women who received 100 mg . As . A. supplementation from approximately 20 weeks of pregnancy had significantly higher levels of As . A. in the whole blood , plasma and blood cells than the unsupplemented group . 4 The value of As . A. supplementation in pregnancy and lactation is discussed Summary This study was conducted as part of a double-blind r and omised placebo-controlled trial , the aim of which was to determine whether vitamin C could reduce the recurrence risk of pre-term labour .  In this study , women with a history of pre-term labour in a preceding pregnancy were r and omised to receive either 250 mg vitamin C or a matching placebo twice daily until 34 weeks ' gestation . They attended a dedicated pre-term labour clinic every 2 weeks . All women were screened for bacterial vaginosis ( BV ) at each visit . It was first determined that vitamin C did not have any effect on the presence of BV . Women who were diagnosed with BV before 20 weeks ' gestation were at higher risk of delivering pre-term than those who developed BV after 20 weeks BACKGROUND Oxidative stress has been implicated in the pathophysiology of pre-eclampsia . This r and omised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia . METHODS 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were r and omly assigned vitamin C ( 1000 mg/day ) and vitamin E ( 400 IU/day ) or placebo at 16 - 22 weeks ' gestation . Plasma markers of endothelial activation ( plasminogen-activator inhibitor 1 [ PAI-1 ] ) and placental dysfunction ( PAI-2 ) were measured every month until delivery . Pre-eclampsia was assessed by the development of proteinuric hypertension . Analyses were done by intention to treat , and in the cohort who completed the study . FINDINGS Supplementation with vitamins C and E was associated with a 21 % decrease in the PAI-1/PAI-2 ratio during gestation ( 95 % CI 4 - 35 , p=0.015 ) . In the intention-to-treat cohort , pre-eclampsia occurred in 24 ( 17 % ) of 142 women in the placebo group and 11 ( 8 % ) of 141 in the vitamin group ( adjusted odds ratio 0.39 [ 0.17 - 0.90 ] , p=0.02 ) . In the cohort who completed the study ( 81 placebo group , 79 vitamin group ) , the odds ratio for pre-eclampsia was 0.24 ( 0.08 - 0.70 , p=0.002 ) . INTERPRETATION Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease . Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different population OBJECTIVE The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of  premature rupture of the membranes ( PROM ) .  STUDY DESIGN A placebo-controlled , double-blind trial was conducted . PROM and preterm PROM ( PPROM ) were planned secondary outcomes of the trial . Women between 12(0/7 ) and 19(6/7 ) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were r and omized to daily treatment with both vitamin C ( 1000 mg ) and E ( 400 IU ) or placebo . RESULTS Outcome data for PROM were available for 697 of 739 patients . The rates of PROM ( 37/349 [ 10.6 % ] vs 19/348 [ 5.5 % ] ; adjusted risk ratio [ RR ] 1.89 [ 95.42 % CI , 1.11 - 3.23 ] ; P = .015 ) , and PPROM ( 16/349 [ 4.6 % ] vs 6/348 [ 1.7 % ] ; RR 2.68 [ 1.07 - 6.71 ] ; P = .025 ) were increased in the antioxidant group . CONCLUSION Contrary to expectations , vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM BACKGROUND Preterm infants are at increased risk of oxidative stress and free-radical mediated diseases partly related to deficient antioxidant state . The purpose of this study was to investigate if maternal supplementation of antioxidant vitamins prior to delivery would reduce the oxidative stress in the mothers and their infants . STUDY DESIGN A pilot case-control study . PATIENTS AND METHODS Five mothers at risk of preterm delivery between 30 and 36 weeks were given a daily oral dose of betacarotene 20 mg , vitamin E 167.8 mg and vitamin C 1000 mg until delivery . Plasma levels of MDA and vitamins A , E and beta-carotene  were measured prior to treatment in mothers and at delivery in both mothers and neonates . Seven mother-infant pairs comparable in gestation and birthweight acted as controls . RESULTS In the supplemented group , median maternal plasma MDA at delivery was significantly lower compared to the pretreatment level ( 1.9 vs. 3.2 micromol/l , p=0.04 ) and it was also lower than the control group ( 1.9 vs. 3.65 micromol/l , p<0.001 ) . In the supplemented group , median maternal plasma vitamin E at delivery was significantly higher than the levels prior to treatment ( 46 vs. 31 micromol/l , p=0.007 ) in the same group and those at delivery in the control group ( 46 vs. 30 micromol/l , p=0.03 ) . There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers , but it did not reach statistical significance . CONCLUSION A short supplementation of multiple antioxidant vitamins to a small sample of preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates . Larger studies probably using larger doses are needed to evaluate the efficacy of this strategy 60 pregnant women underwent a double blind trial with calcium or ascorbic acid ( 1 g twice daily ) as treatment for leg cramps .  There was no significant difference between the two treatment groups with respect to clinical improvement . In 14 out of 60 patients the symptoms were totally abolished and in another 27 patients the symptoms were significantly decreased by the treatment ( irrespective of drug used ) . In 17 patients the symptoms were unaffected while only two patients experienced an increase in frequency of their leg cramps during therapy . Serum total and ionized calcium concentrations , serum total magnesium and albumin concentrations were determined and were not significantly changed throughout therapy in any of the groups . No biochemical differences were found between the different treatment regimens or between those patients relieved or not relieved of their symptoms . Serum magnesium concentrations were at or just below the lower normal limit ( for non pregnant women ) in treated women and pregnant controls IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development , with lifelong decreases in pulmonary function and increased asthma risk . In a primate model , vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function . OBJECTIVE To determine if newborns of pregnant smokers r and omized to receive daily vitamin C would have improved results of pulmonary function tests ( PFTs ) and decreased wheezing compared with those r and omized to placebo . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011 . One hundred fifty-nine newborns of r and omized pregnant smokers ( 76 vitamin C treated and 83 placebo treated ) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs . Follow-up assessment including wheezing was assessed through age 1 year , and PFTs were performed at age 1 year . INTERVENTIONS Pregnant women were r and omized to receive vitamin C ( 500 mg/d ) ( n = 89 ) or placebo ( n = 90 ) . MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function ( ratio of the time to peak tidal expiratory flow to expiratory time [ TPTEF : TE ] and passive respiratory compliance per kilogram [ Crs/kg ] ) within 72 hours of age . Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year . A subgroup of pregnant smokers and nonsmokers had genotyping performed . RESULTS Newborns of women r and omized to vitamin C ( n = 76 ) , compared with those r and omized to placebo ( n = 83 ) , had improved pulmonary function as measured by TPTEF : TE ( 0.383 vs 0.345 [ adjusted 95 % CI for difference , 0.011 - 0.062 ] ; P = .006 ) and Crs/kg ( 1.32 vs 1.20 mL/cm H2O/kg [ 95 % CI , 0.02 - 0.20 ] ; P = .01 ) . Offspring of women r and omized to vitamin C had significantly decreased wheezing through age 1 year ( 15/70 [ 21 % ] vs 31/77 [ 40 % ] ; relative risk , 0.56 [ 95 % CI , 0.33 - 0.95 ] ; P = .03 ) . There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups . The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor ( rs16969968 ) ( P < .001 for interaction ) . CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring . Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00632476 INTRODUCTION Maternal tobacco use increases the incidence of numerous adverse pregnancy outcomes including miscarriage , small for gestational age infants , spontaneous preterm birth and placental abruption . OBJECTIVES We evaluated the relationship between prenatal vitamin C/E supplementation and perinatal outcomes by maternal smoking status . METHODS Secondary analysis of a multicenter trial of vitamin C/E starting at 9 - 16 weeks in low-risk nulliparous women with singletons . We examined the effect of vitamin supplementation by reported smoker or non-smoker at time of r and omization . The primary outcomes were preeclampsia ( new onset hypertension and proteinuria ) and a composite outcome of severe pregnancy associated hypertension ( severe hypertension OR mild or severe hypertension with elevated liver enzymes , elevated serum creatinine , thrombocytopenia , eclamptic seizure , fetal growth restriction , medically indicated preterm birth or perinatal death ) . Perinatal outcomes included preterm birth and abruption . The Breslow-Day test was used to ascertain whether there was an interaction between smoking status and vitamin supplementation . RESULTS Of 9969 women , 4993 received vitamins C/E and 4976 received placebo .  The  prevalence of smoking ( 15.6 % overall ; 788 vitamin , 763 placebo ) was similar in treatment groups . The analysis of vitamin C/E by smoking status for perinatal outcomes is given ( Table 1 ) . The effect of prenatal vitamin C/E on the risk preeclampsia or pregnancy associated hypertension composite outcome did not differ by smoking status . Vitamin C/E was protective for placental abruption and preterm birth among smokers . CONCLUSION The effect of vitamin C/E supplementation on preeclampsia/pregnancy associated hypertension did not differ by smoking status . However , vitamin C/E supplementation was associated with a > 40 % reduction in placental abruption and > 30 % reduction in preterm birth among smokers warranting further study . ACKNOWLEDGEMENT This project supported in part by National Institutes of Health Grant PO1-HD30367
BACKGROUND Vitamin C supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia , intrauterine growth restriction and maternal anaemia .
There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy .
OBJECTIVES To evaluate the effects of vitamin C supplementation , alone or in combination with other separate supplements on pregnancy outcomes , adverse events , side effects and use of health re sources .