Effect of Ascorbic Acid Supplementation in Pregnancy on Anemia (AAA) (AAA)

September 21, 2022 updated by: David S. McKenna, Fetal Medicine Foundation
A. Anemia is a common problem affecting pregnancy and can result in profound consequences to both the mother and the growing fetus. Current treatment usually includes administration of oral or IV iron, or blood transfusions. Vitamin C is known to affect iron metabolism and has been shown to improve outcomes when used in addition to iron, however, few studies have been performed in pregnancy. The primary aim of this study is to identify the effects of vitamin C on anemia in pregnancy. The Investigators propose a double-blind, randomized placebo controlled trial of 1000mg vitamin C supplementation in 200 low risk pregnancies with iron-deficiency anemia. All newly enrolled patients, who meet inclusion and exclusion criteria, will receive the standard of care evaluation and treatment for anemia in pregnancy. Additionally, patients will be randomized to receive either placebo or vitamin C and compliance monitored with a pill diary. Data will be analyzed by T tests and Mann-Whitney U test. If the data shows a positive statistical significance, vitamin C may be a useful supplement to iron in treating anemia.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

A. Anemia is the most common hematological abnormality during pregnancy and was found to affect 24.1% of pregnant women in a WHO study.2 The most common types of anemia affecting pregnancy are iron-deficiency and acute blood loss. Vitamin C, also known as ascorbic acid, has been well documented to play an active role in the absorption and metabolism of iron from the gut.6 Vitamin C has been used in studies to treat anemic non-pregnant women resulting in significant increases in hemoglobin levels. Similar effects have been found in multiple studies using vitamin C as adjunct treatment for hemodialysis patients with non-responsive anemia.10,12 Vitamin C has already been extensively studied in pregnant women for its effects on preeclampsia, preterm birth, neonatal morbidity and other outcomes, and found to have no adverse effects in doses as high as 1000mg daily or in combination with other medications.8 After an extensive literature search, very few studies have been performed assessing the effect on hemoglobin levels after vitamin C supplementation. One study by Sharma et al. supplemented pregnant women with 500mg vitamin C and found a 18.04% increase in hemoglobin compared to 5.49% in the control.11 A Cochran Review of 29 studies did not discuss or evaluate the effects of vitamin C on anemia.8 Due to the minimal side-effect profile and potential benefits of successfully treating anemia, further research in the area is needed.

V. SPECIFIC AIMS OR OBJECTIVES A. To perform a double-blinded, randomized placebo controlled trial of 1000mg vitamin c supplementation on iron-deficiency anemia in low-risk pregnancies.

VI. SIGNIFICANCE TO PATIENT, INSTITUTION, PROFESSION, OR ALL A. Anemia has been associated with adverse maternal and fetal outcomes, to include, but not limited to low birth weight, preterm delivery, perinatal mortality and postpartum depression.1 Per ACOG guidelines, all pregnant women should be screened for anemia, evaluated for causes and provided supplemental iron. A study by Sharma et al has already demonstrated a significant increase in hemoglobin levels in pregnancy with 500mg vitamin C supplementation.11 Due to the paucity of research of vitamin C in pregnancy, further studies are needed to determine reproducibility.

VII. METHODS A. The investigators plan to enroll 200 patients total, 100 per arm. Potential subjects will be screened by study personal from the new intakes for prenatal care in the Five Rivers Center for Women's Health. A complete blood count (CBC) is obtained as standard of care at the first prenatal visit. The CBC includes hemoglobin level, hematocrit, and red blood cell indices (i.e. MCV and MCH). Pregnant women in the first half of their pregnancy who are found to have a hematocrit level less than 33% (Caucasian and other races), and less than 31% (African American women), will be potentially eligible for enrollment. Women who are noted to be anemic per these thresholds will have iron studies (iron, transferrin, ferritin) and hemoglobin electrophoresis (if not already performed), as part of the standard of care for the evaluation of anemia during pregnancy.1 Inclusion criteria consists of gestational age at enrollment less than 20 0/7 weeks, singleton gestation, iron deficiency anemia defined as maternal serum ferritin levels less than 15 micrograms/dL, and planned delivery at Miami Valley Hospital. Exclusion criteria consist of vitamin C use >150mg/day (typical prenatal vitamin contains 60mg Vitamin C), diabetes (gestational, types 1,2); chronic medical disease; known or discovered hemoglobinopathy (including heterozygous states); known metabolic disease that may contribute to impaired iron absorption (including a history of bariatric surgery, renal disease and an inability to tolerate oral iron); known fetal abnormalities; participation in another interventional trial; illicit drug or alcohol use. All risks/benefits will be reviewed and all questions answered prior to the patient being enrolled. Written informed consent will be obtained by a study investigator or qualified personnel. Gestational dating will be based upon the best obstetrical estimate.

B. A compounding pharmacy will make 30,000 placebo capsules containing an inert substance (i.e. silica based cellulose), identical appearing to 30,000 capsules of 500mg vitamin C. The pharmacy will package 300 pills of either placebo or vitamin C into 200 boxes, labeled only with the project name and a number. A key containing the known substance of each box and number will be kept by the pharmacy until the end of the study. The boxes will be stored in a secured area of the principal investigators office. The boxes will be taken to Five Rivers Women's Health Clinic to be distributed to enrolled patients. Once enrolled, patients will be given a random box and instructed to take 1 pill twice daily. Patients will be instructed to record pill usage daily for compliance. The patient's name and assigned box number will be kept in a locked cabinet. At the end of the study, the two keys will be compared to determine who received placebo or vitamin C. Both groups will receive prescriptions for ferrous sulfate, 65mg taken once daily; docusate sodium to be taken as needed for constipation; and prenatal vitamins once daily. Patients will receive follow up labs as part of the standard of care for anemia, to include at 28 week, and at delivery. All data will be collected in an Excel spreadsheet, with patient identifiers removed. Data will be analyzed by applying basic T tests and the Mann-Whitney-U test to determine the changes in lab values of hemoglobin, hematocrit, iron, transferrin, ferritin between experimental and control before and after treatment.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Dayton, Ohio, United States, 45409
        • Five Rivers Health Centers

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • gestational age at enrollment less than 20 0/7 weeks,
  • singleton gestation,
  • iron deficiency anemia defined as maternal serum ferritin levels less than 15 micrograms/dL, and
  • planned delivery at Miami Valley Hospital.

Exclusion Criteria:

  • vitamin C use >150mg/day (typical prenatal vitamin contains 60mg Vitamin C),
  • diabetes (gestational, types 1,2); chronic medical disease;
  • known or discovered hemoglobinopathy (including heterozygous states);
  • known metabolic disease that may contribute to impaired iron absorption (including a history of bariatric surgery, renal disease and an inability to tolerate oral iron);
  • known fetal abnormalities;
  • participation in another interventional trial;
  • illicit drug or alcohol use

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Iron + Vitamin C
One iron tablet once a day plus a 500 mg vitamin C tablet twice a day until delivery.
Dietary supplement: Vitamin C
1000mg Vitamin C per day
Other Names:
  • Ascorbic Acid
No Intervention: Iron + Placebo
One iron tablet once a day plus a placebo tablet twice a day until delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum hemoglobin
Time Frame: To be measured at 1st prenatal visit, 28 weeks', and at delivery
Change in serum hemoglobin
To be measured at 1st prenatal visit, 28 weeks', and at delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fetal Medicine Foundation

Collaborators

Wright State University
Five Rivers Health Centers

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2019

Primary Completion (Actual)

March 30, 2022

Study Completion (Actual)

March 30, 2022

Study Registration Dates

First Submitted

May 25, 2018

First Submitted That Met QC Criteria

June 19, 2018

First Posted (Actual)

June 21, 2018

Study Record Updates

Last Update Posted (Actual)

September 22, 2022

Last Update Submitted That Met QC Criteria

September 21, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAA-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Data will be used by the study team to test the study hypothesis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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