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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A, 1 | Active Comparator |
| |
| A, 2 | Experimental |
| |
| A, 3 | Experimental | Multiple micronutrient supplement |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| folic acid | Dietary Supplement | pills by mouth, one per day, from the first prenatal visit until delivery, 400 micrograms (mcg) folic acid |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 20 weeks gestation to 6 days postpartum |
| Measure | Description | Time Frame |
|---|---|---|
| Maternal anemia | 24-28 weeks gestation | |
| Maternal anemia | 4-8 weeks postpartum | |
| Infant gestational age at birth, preterm delivery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Weicheng You, MD, MBA | Peking University Health Science Center, Beijing China | Principal Investigator |
| Jianmeng Liu, MD, PhD | Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing China | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fengrun Maternal and Child Health Institute | Fengrun | Hebei | 064000 | China | ||
| Yuanshi Maternal and Child Health Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35265334 | Derived | 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. | |
| 33594802 | Derived | Liu 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. |
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| ID | Term |
|---|---|
| D066087 | Perinatal Death |
| D050497 | Stillbirth |
| D000740 | Anemia |
| D001724 | Birth Weight |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003643 | Death |
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| ID | Term |
|---|---|
| D005492 | Folic Acid |
| D007501 | Iron |
| C067316 | Geritol |
| D008903 | Minerals |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| folic acid plus iron | Dietary 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 minerals | Dietary Supplement | 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 |
|
|
| delivery |
| Infant birth weight, low birth weight | at birth |
| Infant low weight-for-height | infant age 6 months and 12 months |
| Infant anemia | 6 months and 12 months of age |
| maternal gastrointestinal side effects | monthly from a month after enrollment until delivery |
| Huaiyang |
| Hebei |
| 051130 |
| China |
| Laoting Maternal and Child Health Institute | Laoting | Hebei | 063600 | China |
| Mancheng Maternal and Child Health Institute | Mancheng | Hebei | 072150 | China |
| Xianghe Maternal and Child Health Institute | Xianghe | Hebei | 065400 | China |
| 29428785 | Derived | Chen 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. |
| 27263403 | Derived | Zhang 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. |
| 23303315 | Derived | Liu 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. |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005313 | Fetal Death |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D006571 | Heterocyclic Compounds |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D028561 | Transition Elements |
| D008670 | Metals |