ascorbic-acid and Premature-Birth

To assess the evidence available on the use of vitamin C supplementation greater than recommended dietary intake to reduce preterm birth rates.. Systematic review of randomized controlled trials using vitamin C alone or with one other supplement other than iron. Trials must report preterm birth rates but can have other primary outcomes. Preterm birth is defined as birth at less than 37 weeks' gestational age for this review. Review focused on studies with populations representative of Organization for Economic Co-operation and Development countries.. Inadequate level of evidence on the use of vitamin C alone to prevent preterm birth rates in low-risk populations based on one study. Three studies provided convincing evidence of no benefit in low-risk groups of use of vitamins C and E combined. Three studies provided adequate evidence of no benefit in high-risk groups of use of vitamins C and E combined.. The available evidence supports no benefit gained from using vitamin C to prevent preterm birth. Evidence does not support limiting use of vitamin C supplementation for other indications.

Topics: Antioxidants; Ascorbic Acid; Dietary Supplements; Drug Therapy, Combination; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Vitamin E

Preeclampsia, intrauterine growth restriction (IUGR), and placental abruption are obstetrical conditions that constitute the syndrome of ischemic placental disease or IPD, the leading cause of indicated preterm birth and an important cause of neonatal morbidity and mortality. While the phenotypic manifestations vary significantly for preeclampsia, IUGR, and abruption, these conditions may share a common underlying etiology as evidenced by: (1) shared clinical risk factors, (2) increased recurrence risk across pregnancies as well as increased co-occurrence of IPD conditions within a pregnancy, and (3) findings that suggest the underlying pathophysiologic processes may be similar. IPD is of major clinical importance and accounts for a large proportion of indicated preterm delivery ranging from the periviable to late preterm period. Successful prevention of IPD and resultant preterm delivery could substantially improve neonatal and maternal outcomes. This article will review the following topics: (1) The complicated research literature on aspirin and the prevention of preeclampsia and IUGR. (2) Research evidence on other medical interventions to prevent IPD. (3) New clinical interventions currently under investigations, including statins. (4) Current clinical recommendations for prevention of ischemic placental disease.

Topics: Abruptio Placentae; Anticoagulants; Ascorbic Acid; Aspirin; Calcium, Dietary; Dietary Supplements; Fatty Acids, Omega-3; Female; Fetal Growth Retardation; Fibrinolytic Agents; Humans; Ischemia; Placenta; Placenta Diseases; Pre-Eclampsia; Pregnancy; Premature Birth; Risk Factors; Vitamin E

Benefit of micronutrient supplementation on female fertility.. Reports of randomized trials are rare. Most studies are focused on multivitamin supplementations. For some micronutrients, a positive impact on fertility could be shown. This article reviews the available clinical studies as well as the pathophysiological background of possible effects and summarizes the potential benefits of selected micronutrients on female fertility.. Apart from lowering the malformation risk by periconceptional supplementation of folic acid, substitution with different micronutrients, particularly folic acid, vitamin B6, vitamin C, vitamin D, vitamin E, iodine, selenium, iron, and DHA might have a positive impact on infertility treatment. The multivitamin formulation should take the pathophysiology, clinical studies, and upper limits into account.

Topics: Adult; Ascorbic Acid; Birth Weight; Dietary Supplements; Female; Folic Acid; Humans; Infertility, Female; Micronutrients; Neural Tube Defects; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Nutritional Physiological Phenomena; Randomized Controlled Trials as Topic; Selenium; Vitamin B Complex

Vitamin C supplementation may help reduce the risk of pregnancy complications like pre-eclampsia, intrauterine growth restriction and maternal anaemia. There is a need to evaluate the efficacy and safety of vitamin C supplementation in pregnancy.. 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 resources.. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (23 June 2004), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004), MEDLINE, Current Contents and EMBASE.. All randomised or quasi-randomised controlled trials evaluating vitamin C supplementation in pregnant women. Interventions using a multivitamin supplement containing vitamin C or where the primary supplement was iron were excluded.. Two authors independently assessed trials for inclusion, extracted data and assessed trial quality.. Five trials, involving 766 women, are included in this review. No difference was seen between women supplemented with vitamin C alone or combined with other supplements compared with placebo for the risk of stillbirth (relative risk (RR) 0.87, 95% confidence intervals (CI) 0.41 to 1.87, three trials, 539 women), perinatal death (RR 1.16, 95% CI 0.61 to 2.18, two trials, 238 women), birthweight (weighted mean difference (WMD) -139.00 g, 95% CI -517.68 to 239.68, one trial, 100 women) or intrauterine growth restriction (RR 0.72, 95% CI 0.49 to 1.04, two trials, 383 women). Women supplemented with vitamin C alone or combined with other supplements were at increased risk of giving birth preterm (RR 1.38, 95% CI 1.04 to 1.82, three trials, 583 women). Significant heterogeneity was found for neonatal death and pre-eclampsia. No difference was seen between women supplemented with vitamin C combined with other supplements for the risk of neonatal death (RR 1.73, 95% CI 0.25 to 12.12, two trials, 221 women), using a random-effects model. For pre-eclampsia, women supplemented with vitamin C combined with other supplements were at decreased risk when using a fixed-effect model (RR 0.47, 95% CI 0.30 to 0.75, four trials, 710 women); however, this difference could not be demonstrated when using a random-effects model (RR 0.52, 95% CI 0.23 to 1.20, four trials, 710 women).. The data are too few to say if vitamin C supplementation, alone or combined with other supplements, is beneficial during pregnancy. Preterm birth may have been increased with vitamin C supplementation.

Topics: Ascorbic Acid; Dietary Supplements; Female; Fetal Death; Humans; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic

Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes.. Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race.. In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81).. Higher preconception antioxidant levels are not associated with better birth outcomes.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Black or African American; Carotenoids; Female; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Premature Birth; White People; Young Adult

To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB).. A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity.. Of 9,867 women, 10.4% (. Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB.

Topics: Adolescent; Adult; Ascorbic Acid; Birth Weight; Delivery, Obstetric; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Small for Gestational Age; Intensive Care Units, Neonatal; Logistic Models; Male; Multivariate Analysis; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Respiratory Distress Syndrome, Newborn; Retrospective Studies; United States; Vitamin E; Young Adult

Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking.. A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations.. We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction.. The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption.. There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046).. In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

Topics: Abruptio Placentae; Adolescent; Adult; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Female; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Premature Birth; Smoking; Vitamin E; Vitamins; Young Adult

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, Uganda.. This was a (parallel, balanced randomization, 1:1) placebo randomized 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 randomized to take 1000mg 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 randomized 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.. Of the 932 women recruited; 466 were randomized 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).. 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.. This study was registered at the Pan African Clinical Trial Registry, PACTR201210000418271 on 25th October 2012.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Female; Humans; Incidence; Pre-Eclampsia; Pregnancy; Premature Birth; Severity of Illness Index; Stillbirth; Uganda; Young Adult

To estimate whether maternally administered vitamins C and E lower the risk of spontaneous preterm birth.. This is a secondary analysis of a randomized, 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).. Of the 10,154 women randomized, 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.. 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.. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135707.. I.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Fetal Membranes, Premature Rupture; Humans; Pregnancy; Premature Birth; Vitamin E; Young Adult

Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes.. In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death.. The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001).. Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].).

Topics: Abortion, Spontaneous; Adult; Ascorbic Acid; Birth Weight; Double-Blind Method; Female; Fetal Death; HIV Seronegativity; Humans; Incidence; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Pregnancy; Pregnancy Outcome; Premature Birth; Tanzania; Vitamin B Complex; Vitamin E; Vitamins

Haemoglobin variants and preeclampsia (PE) are associated with adverse fatal events of which oxidative stress may be an underlying factor. Oxidative stress (OS) among preeclamptic women with haemoglobin variants has been well established. It is, however, unclear whether haemoglobin variants induce OS to aggravate the risk of adverse foeto-maternal outcomes in pregnant women with preeclampsia. We measured the levels of OS biomarkers and determined the association between haemoglobin variants, and adverse foeto-maternal outcomes among pregnant women with PE.. This multi-centre prospective study recruited 150 PE women from three major health facilities in both Bono and Bono east regions of Ghana from April to December 2019. Haemoglobin variants; HbAS, HbSS, HbSC, HbCC, and HbAC were determined by haemoglobin electrophoresis. OS biomarkers such as malondialdehyde (MDA), catalase (CAT), vitamin C, and uric acid (UA) along with haematological and biochemical parameters were estimated using standard protocol. Adverse pregnancy complications (APCs) such as post-partum haemorrhage (PPH), HELLP (Haemolysis, Elevated liver enzymes, Low platelet count) syndrome, preterm delivery, neonatal intensive care unit (NICU) admission, and neonatal jaundice were recorded.. Of the 150 pregnant women with preeclampsia, the distribution of haemoglobin AA, AS, AC, CC, SS and SC phenotypes were 66.0%, 13.3%, 12.7%, 3.3%, 3.3% and 1.3%, respectively. The most prevalent foeto-maternal outcomes among PE women were NICU admission (32.0%) followed by PPH (24.0%), preterm delivery (21.3%), HELLP syndrome (18.7%), and neonatal jaundice (18.0%). Except for vitamin C level which was significantly higher in patients with at least a copy of Haemoglobin S variant than those with at least a copy of Haemoglobin C variant (5.52 vs 4.55; p = 0.014), levels of MDA, CAT, and UA were not statistically significantly different across the various haemoglobin variants. Multivariate logistic regression model showed that participants with HbAS, HbAC, having at least a copy of S or C and participants with HbCC, SC, SS had significantly higher odds of neonatal jaundice, NICU admission, PPH and HELLP syndrome compared to participants with HbAA.. Reduced levels of vitamin C are common among preeclamptics with at least one copy of the HbC variant. Haemoglobin variants in preeclampsia contribute to adverse foeto-maternal outcomes with Haemoglobin S variants being the most influencing factor for PPH, HELLP, preterm labour, NICU admission, and neonatal jaundice.

Topics: Ascorbic Acid; Biomarkers; Female; Ghana; HELLP Syndrome; Hemoglobin, Sickle; Humans; Infant, Newborn; Jaundice, Neonatal; Oxidative Stress; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Premature Birth; Prospective Studies

Nitrosatable drugs react with nitrite in the stomach to form N-nitroso compounds, observed in animal models to result in adverse pregnancy outcomes, such as birth defects and reduced fetal weight. Previous studies examining prenatal exposure to medications classified as nitrosatable have reported an increased risk of preterm births (PTBs) and small-for-gestational-age (SGA) infants.. Using data from mothers (controls) of babies without major birth defects from the National Birth Defects Prevention Study, prenatal nitrosatable drug usage by trimester and month of gestation was examined in relation to PTBs and SGA infants.. Positive associations were observed with nitrosatable drug use and PTBs, with the strongest relationship with second trimester exposure (adjusted hazard ratio [aHR] 1.37, [95% confidence interval (CI) 1.10, 1.70]). Of the nitrosatable functional groups, secondary amines were the most notable, with a higher association among women with second (aHR 1.37, [95% CI 1.05, 1.79]) and third (aHR 1.34, [95% CI 1.02, 1.76]) trimester exposure compared with women with no prenatal nitrosatable drug use. Among SGA infants, a borderline association was noted with amide exposure during the third trimester (adjusted odds ratio 1.43 [95% confidence interval [CI] 1.00, 2.05]).. Prenatal exposure to nitrosatable drugs during the second and third trimester of pregnancy, particularly secondary amines, might increase the risk of PTBs. However, prenatal exposure to nitrosatable drugs was not associated with SGA infants, with the exception of amide drugs.

Topics: Adolescent; Adult; Amides; Amines; Ascorbic Acid; Case-Control Studies; Dietary Supplements; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Male; Pregnancy; Pregnancy Trimesters; Premature Birth; Risk Factors; United States; Young Adult

Topics: Abruptio Placentae; Ascorbic Acid; Dietary Supplements; Female; Humans; Pregnancy; Premature Birth; Smoking Cessation; Tobacco Use Cessation Devices; Vitamin E

Vitamin C has been the focus of epidemiologic investigation in preterm delivery (<37 weeks' gestation), which is a leading cause of neonatal mortality and birth-related morbidity. There are two sodium-dependent membrane transporters encoded by SLC23A1 and SLC23A2, which have key roles in human vitamin C metabolism and which control dietary uptake, reabsorption, and tissue distribution of vitamin C. Using maternal DNA, the authors evaluated common single-nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2 in a nested case-control analysis of the Pregnancy, Infection, and Nutrition Study (1995-2000) cohort. Of the associations observed for both haplotypes in SLC23A1 and individual SNPs in SLC23A2, the most robust finding is with an intron 2 variant in SLC23A2. Heterozygotes and homozygotes for this variant had a 1.7-fold (95% confidence interval: 0.9, 3.3) and a 2.7-fold (95% confidence interval: 1.2, 6.3) elevation in the risk of spontaneous preterm birth, respectively. Semi-Bayesian hierarchical regression analysis, which simultaneously adjusted for multiple SNPs within the same gene, gave comparable results. The authors' findings link genetic variants in the vitamin C transporters to spontaneous preterm birth, which may explain previous dietary associations. If the findings from this study are confirmed, they may serve as the foundation for genetic risk assessment of nutritional pathways in preterm birth.

Topics: Adult; Alleles; Ascorbic Acid; Black or African American; Case-Control Studies; Female; Genetic Variation; Haplotypes; Humans; North Carolina; Organic Anion Transporters, Sodium-Dependent; Polymorphism, Single Nucleotide; Pregnancy; Premature Birth; Risk Factors; Sodium-Coupled Vitamin C Transporters; Symporters; White People