Clinical trial NCT00133744: Impact of Prenatal Vitamin/Mineral Supplements on Perinatal Mortality
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Perinatal Mortality
Stillbirth
Neonatal Mortality
Keywords: pregnancy
vitamins
minerals
supplements
mortality
prenatal
perinatal
anemia
birthweight
preterm
iron
micronutrients
Stillbirths
Early neonatal deaths
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
First posted: 2005-08-24
Enrollment: 18962
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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 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).

Eligibility criteria: Inclusion Criteria:

* Live in one of the study counties (Laoting, Mancheng, Fengrun, Xianghe, Yuanshi)
* Can follow instructions
* Can swallow pills

Exclusion Criteria:

* \>= 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

Primary outcomes:
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)
timeFrame: 20 weeks gestation to 6 days postpartum
Secondary outcomes:
measure: Maternal anemia
timeFrame: 24-28 weeks gestation
measure: Maternal anemia
timeFrame: 4-8 weeks postpartum
measure: Infant gestational age at birth, preterm delivery
timeFrame: delivery
measure: Infant birth weight, low birth weight
timeFrame: at birth
measure: Infant low weight-for-height
timeFrame: infant age 6 months and 12 months
measure: Infant anemia
timeFrame: 6 months and 12 months of age
measure: maternal gastrointestinal side effects
timeFrame: monthly from a month after enrollment until delivery
Other outcomes:
Locations:
city: Fengrun
country: China
facility: Fengrun Maternal and Child Health Institute
state: Hebei
city: Laoting
country: China
facility: Laoting Maternal and Child Health Institute
state: Hebei
city: Mancheng
country: China
facility: Mancheng Maternal and Child Health Institute
state: Hebei
city: Xianghe
country: China
facility: Xianghe Maternal and Child Health Institute
state: Hebei
city: Yuanshi
country: China
facility: Yuanshi Maternal and Child Health Institute
state: Hebei
Study officials:
affiliation: Peking University Health Science Center, Beijing China
name: Weicheng You, MD, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing China
name: Jianmeng Liu, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.