Perinatal MortalityPhase 3NCT00133744
Impact of Prenatal Vitamin/Mineral Supplements on Perinatal Mortality
A Phase 3 study testing folic acid, folic acid plus iron and supplements with multiple vitamins and minerals in people with Perinatal Mortality and Stillbirth, run by Centers for Disease Control and Prevention at 5 sites in China.
Trial summary
The purpose of this study is to determine whether a daily prenatal supplement of iron plus folic acid or a daily prenatal supplement with multiple vitamins and minerals given to women from their first prenatal visit through delivery reduces perinatal mortality compared with a daily prenatal supplement of folic acid… Read more about this study
- Who is it for?
- Ages 20 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Perinatal Mortality, Stillbirth, Neonatal Mortality
- What is being tested?
- folic acid, folic acid plus iron and supplements with multiple vitamins and minerals
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18,962 participants
- Where
- 5 sitesChina
- Study dates
- May 2006to Dec 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Live in one of the study counties (Laoting, Mancheng, Fengrun, Xianghe, Yuanshi)
- Can follow instructions
- Can swallow pills
Who cannot join
- >= 20 weeks gestation at enrollment
- Previous live birth
- Anemic (hemoglobin [Hb] <10 g/dl in 1st trimester and < 9.5 g/dl in 2nd trimester) at enrollment
- Current use of iron or other vitamin or mineral supplements (except folic acid)
- Age < 20 years at enrollment
- Under treatment for anemia at enrollment
- Refuse to participate
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Fengrun Maternal and Child Health Institute
Fengrun, Hebei, 064000
Yuanshi Maternal and Child Health Institute
Huaiyang, Hebei, 051130
Laoting Maternal and Child Health Institute
Laoting, Hebei, 063600
Mancheng Maternal and Child Health Institute
Mancheng, Hebei, 072150
Xianghe Maternal and Child Health Institute
Xianghe, Hebei, 065400
About this study
Official title: Impact of Iron/Folic Acid Versus Multimicronutrient Versus Folic Acid Supplements During Pregnancy on Mortality, Morbidity, and Complications During Pregnancy, Labor, and Delivery: A Randomized Controlled Trial in China
The purpose of this study is to determine whether a daily prenatal supplement of iron plus folic acid or a daily prenatal supplement with multiple vitamins and minerals given to women from their first prenatal visit through delivery reduces perinatal mortality compared with a daily prenatal supplement of folic acid alone.
Read the detailed description
In the project area in China, the rate of perinatal mortality (stillbirths and infant deaths within 6 days of birth) is two times that of the United States. Causes of perinatal mortality include, but are not limited to, low birth weight and preterm delivery. Anemia (low hemoglobin) among pregnant women is associated with low birth weight and preterm delivery and also is elevated in the project area. Supplements of iron, folic acid, and other vitamins and minerals can prevent anemia among pregnant women, but the effects of these supplements on other maternal and infant health outcomes are unclear.
Since 1993, the People's Republic of China has recommended that newly married women, and those who plan pregnancy, take 400μg of folic acid daily through the first trimester of pregnancy. Although WHO recommends that pregnant women take iron and folic acid supplements, there is currently no national recommendation that pregnant women in China take iron or other vitamin or mineral supplements (other than folic acid). UNICEF is now testing a prenatal vitamin and mineral supplement in programs to prevent low birth weight. Our study will provide additional information about the health impact of the UNICEF prenatal supplement versus an iron and folic acid supplement versus folic acid alone.
Comparisons:
- Infants of women who receive daily prenatal supplements that contain 400μg folic acid alone, will be compared with infants of women who receive daily supplements that contain 30 mg iron and 400 μg folic acid.
- Infants of women who receive daily supplements that contain 30 mg iron and 400 μg folic acid will be compared with infants of women who receive a daily supplement containing 30 mg iron, 400μg folic acid and other vitamins and minerals (UNICEF formulation).
- Conditions
- Perinatal Mortality, Stillbirth, Neonatal Mortality
- Being tested
- folic acid, folic acid plus iron, supplements with multiple vitamins and minerals
- Keywords
- pregnancy, vitamins, minerals, supplements, mortality, prenatal, perinatal, anemia, birthweight, preterm, iron, micronutrients, Stillbirths, Early neonatal deaths
- Medical subject headings
- Perinatal Death, Stillbirth, Anemia, Birth Weight, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
folic acidDietary supplement
pills by mouth, one per day, from the first prenatal visit until delivery, 400 micrograms (mcg) folic acid
folic acid plus ironDietary supplement
pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid, 30 mg Fe
supplements with multiple vitamins and mineralsDietary supplement
Also called UNIMMAP
pills, one per day, from the first prenatal visit until delivery; folic acid 400 mcg, Fe 30 mg, vitamin(vit) A 800 mcg, vit E 10 mg, vit D 5 mcg, vit C 70 mg, vit B1 1.4 mg, vit B2 1.4 mg, vit B6 1.9 mg, vit B12 2.6 mcg, Niacin 18 mg, Zn 15 mg, Cu 2mg, Iodine 150 mcg, Selenium 65 mcg
| Study group | Role | What they receive |
|---|---|---|
| A, 1 | Active comparator | Not described Receives: Dietary Supplement: folic acid |
| A, 2 | Experimental | Not described Receives: Dietary Supplement: folic acid plus iron |
| A, 3 | Experimental | Multiple micronutrient supplement Receives: Dietary Supplement: supplements with multiple vitamins and minerals |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perinatal mortality, i.e., the number of stillbirths (fetal deaths of 28 weeks or more of gestation) and the number of deaths within the first 0-6 days of life per 1000 births (live births and stillbirths)
Measured: 20 weeks gestation to 6 days postpartum
Secondary outcomes (7)
Maternal anemia
Measured: 24-28 weeks gestation
Maternal anemia
Measured: 4-8 weeks postpartum
Infant gestational age at birth, preterm delivery
Measured: delivery
Infant birth weight, low birth weight
Measured: at birth
Infant low weight-for-height
Measured: infant age 6 months and 12 months
Infant anemia
Measured: 6 months and 12 months of age
maternal gastrointestinal side effects
Measured: monthly from a month after enrollment until delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2005 (estimated)
- Study startMay 2006
- Primary completionDec 2009
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Perinatal MortalityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18,962 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Investigators
- Weicheng You, MD, MBA, Principal investigator, Peking University Health Science Center, Beijing ChinaJianmeng Liu, MD, PhD, Study director, Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00133744
- Sponsor's protocol ID
- CDC-NCCDPHP-4084
- Status last verified
- Mar 2011
- First submitted
- 22 Aug 2005
- Last updated
- 21 Mar 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Si KY, Li HT, Zhou YB, Li ZW, Zhang L, Zhang YL, Ye RW, Liu JM. Cesarean delivery on maternal request and common child health outcomes: A prospective cohort study in China. J Glob Health. 2022 Feb 26;12:11001. doi: 10.7189/jogh.12.11001. eCollection 2022.
PubMed 35265334Liu Y, Li N, Mei Z, Li Z, Ye R, Zhang L, Li H, Zhang Y, Liu JM, Serdula MK. Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial. Matern Child Nutr. 2021 Jul;17(3):e13157. doi: 10.1111/mcn.13157. Epub 2021 Feb 16.
PubMed 33594802Chen S, Li N, Mei Z, Ye R, Li Z, Liu J, Serdula MK. Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: A randomized clinical trial. Clin Nutr. 2019 Feb;38(1):146-151. doi: 10.1016/j.clnu.2018.01.029. Epub 2018 Feb 15.
PubMed 29428785Zhang Y, Jin L, Liu JM, Ye R, Ren A. Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial. J Pediatr. 2016 Aug;175:106-110.e2. doi: 10.1016/j.jpeds.2016.05.011. Epub 2016 Jun 2.
PubMed 27263403Liu JM, Mei Z, Ye R, Serdula MK, Ren A, Cogswell ME. Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China. JAMA Intern Med. 2013 Feb 25;173(4):276-82. doi: 10.1001/jamainternmed.2013.1632.
PubMed 23303315
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Iron/Folic Acid Versus Multimicronutrient Versus Folic Acid Supplements During Pregnancy on Mortality, Morbidity, and Complications During Pregnancy, Labor, and Delivery: A Randomized Controlled Trial in China
- ClinicalTrials.gov ID
- NCT00133744
- Acronym / sponsor ID
- CDC-NCCDPHP-4084
- Conditions
- Perinatal Mortality, Stillbirth, Neonatal Mortality
- Keywords
- pregnancy, vitamins, minerals, supplements, mortality, prenatal, perinatal, anemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18,962 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Study start
- May 2006
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 24 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether a daily prenatal supplement of iron plus folic acid or a daily prenatal supplement with multiple vitamins and minerals given to women from their first prenatal visit through delivery reduces perinatal mortality compared with a daily prenatal supplement of folic acid alone.
Detailed description
In the project area in China, the rate of perinatal mortality (stillbirths and infant deaths within 6 days of birth) is two times that of the United States. Causes of perinatal mortality include, but are not limited to, low birth weight and preterm delivery. Anemia (low hemoglobin) among pregnant women is associated with low birth weight and preterm delivery and also is elevated in the project area. Supplements of iron, folic acid, and other vitamins and minerals can prevent anemia among pregnant women, but the effects of these supplements on other maternal and infant health outcomes are unclear.
Since 1993, the People's Republic of China has recommended that newly married women, and those who plan pregnancy, take 400μg of folic acid daily through the first trimester of pregnancy. Although WHO recommends that pregnant women take iron and folic acid supplements, there is currently no national recommendation that pregnant women in China take iron or other vitamin or mineral supplements (other than folic acid). UNICEF is now testing a prenatal vitamin and mineral supplement in programs to prevent low birth weight. Our study will provide additional information about the health impact of the UNICEF prenatal supplement versus an iron and folic acid supplement versus folic acid alone.
Comparisons:
- Infants of women who receive daily prenatal supplements that contain 400μg folic acid alone, will be compared with infants of women who receive daily supplements that contain 30 mg iron and 400 μg folic acid.
- Infants of women who receive daily supplements that contain 30 mg iron and 400 μg folic acid will be compared with infants of women who receive a daily supplement containing 30 mg iron, 400μg folic acid and other vitamins and minerals (UNICEF formulation).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A, 1 | Active comparator | Dietary Supplement: folic acid |
| A, 2 | Experimental | Dietary Supplement: folic acid plus iron |
| A, 3 | Experimental | Dietary Supplement: supplements with multiple vitamins and mineralsMultiple micronutrient supplement |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Live in one of the study counties (Laoting, Mancheng, Fengrun, Xianghe, Yuanshi)
- Can follow instructions
- Can swallow pills
Key exclusion criteria (7 listed)
- >= 20 weeks gestation at enrollment
- Previous live birth
- Anemic (hemoglobin [Hb] <10 g/dl in 1st trimester and < 9.5 g/dl in 2nd trimester) at enrollment
- Current use of iron or other vitamin or mineral supplements (except folic acid)
- Age < 20 years at enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| folic acidpills by mouth, one per day, from the first prenatal visit until delivery, 400 micrograms (mcg) folic acid | Dietary supplement | A, 1 |
| folic acid plus ironpills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid, 30 mg Fe | Dietary supplement | A, 2 |
| supplements with multiple vitamins and mineralsAlso: UNIMMAPpills, one per day, from the first prenatal visit until delivery; folic acid 400 mcg, Fe 30 mg, vitamin(vit) A 800 mcg, vit E 10 mg, vit D 5 mcg, vit C 70 mg, vit B1 1.4 mg, vit B2 1.4 mg, vit B6 1.9 mg, vit B12 2.6 mcg, Niacin 18 mg, Zn 15 mg, Cu 2mg, Iodine 150 mcg, Selenium 65 mcg | Dietary supplement | A, 3 |
Primary outcome
Perinatal mortality, i.e., the number of stillbirths (fetal deaths of 28 weeks or more of gestation) and the number of deaths within the first 0-6 days of life per 1000 births (live births and stillbirths)
Time frame: 20 weeks gestation to 6 days postpartum
7 secondary outcomes
Maternal anemia
Time frame: 24-28 weeks gestation
Maternal anemia
Time frame: 4-8 weeks postpartum
Infant gestational age at birth, preterm delivery
Time frame: delivery
Infant birth weight, low birth weight
Time frame: at birth
Infant low weight-for-height
Time frame: infant age 6 months and 12 months
Infant anemia
Time frame: 6 months and 12 months of age
maternal gastrointestinal side effects
Time frame: monthly from a month after enrollment until delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2011.
- Derived from this study: PubMed 35265334Si KY, Li HT, Zhou YB, Li ZW, Zhang L, Zhang YL, Ye RW, Liu JM. Cesarean delivery on maternal request and common child health outcomes: A prospective cohort study in China. J Glob Health. 2022 Feb 26;12:11001. doi: 10.7189/jogh.12.11001. eCollection 2022.
- Derived from this study: PubMed 33594802Liu Y, Li N, Mei Z, Li Z, Ye R, Zhang L, Li H, Zhang Y, Liu JM, Serdula MK. Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial. Matern Child Nutr. 2021 Jul;17(3):e13157. doi: 10.1111/mcn.13157. Epub 2021 Feb 16.
- Derived from this study: PubMed 29428785Chen S, Li N, Mei Z, Ye R, Li Z, Liu J, Serdula MK. Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: A randomized clinical trial. Clin Nutr. 2019 Feb;38(1):146-151. doi: 10.1016/j.clnu.2018.01.029. Epub 2018 Feb 15.
- Derived from this study: PubMed 27263403Zhang Y, Jin L, Liu JM, Ye R, Ren A. Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial. J Pediatr. 2016 Aug;175:106-110.e2. doi: 10.1016/j.jpeds.2016.05.011. Epub 2016 Jun 2.
- Derived from this study: PubMed 23303315Liu JM, Mei Z, Ye R, Serdula MK, Ren A, Cogswell ME. Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China. JAMA Intern Med. 2013 Feb 25;173(4):276-82. doi: 10.1001/jamainternmed.2013.1632.
Related trials for Perinatal Mortality
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e-Perinatal Butterfly: An Embedded Study for Parents Experiencing Perinatal Loss
Depressive Symptoms, Perinatal Loss
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Weicheng You, MD, MBA principal investigator
Peking University Health Science Center, Beijing China
Jianmeng Liu, MD, PhD study director
Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing China
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing folic acid, folic acid plus iron and supplements with multiple vitamins and minerals in people with Perinatal Mortality and Stillbirth, run by Centers for Disease Control and Prevention at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perinatal mortality, i.e., the number of stillbirths (fetal deaths of 28 weeks or more of gestation) and the number of deaths within the first 0-6 days of life per 1000 births (live births and stillbirths) (time frame: 20 weeks gestation to 6 days postpartum). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00133744, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2011.