Clinical trial NCT02537392: Multi-micronutrient Supplementation During Peri-conception and Congenital Heart Disease
Official title: Primary Prevention of Multi-micronutrient Supplementation During Peri-conception Against Congenital Heart Disease: A Community-based Randomised Controlled Trial in China
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Heart Disease
Lead sponsor: Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2015-09-01
Enrollment: 7315
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether daily oral supplements of vitamin B complex along with folic acid or supplements of iron plus folic acid given to women during peri-conception can reduce the risk of congenital heart disease when compared with folic acid alone.

Detailed description: Congenital heart disease (CHD) is among the most prevalent congenital abnormalities with an incidence of about 8-12/1,000 live births, and is also the leading cause of infant morbidity and death from birth defects. A series of studies pointed out that the poor nutritional status of the mother during peri-conception might be the important cause of CHD. In maternal folic acid/ vitamin B deficiency homocysteine accumulates in the serum, and elevated circulating homocysteine concentrations have been associated with the risk of CHD. However, it is still questionable whether multiple vitamin B supplements during peri-conception can reduce CHD risk more effectively compared with the supplement of folic acid alone. Moreover, one randomized controlled trial performed in Shaanxi China confirmed that the supplement of iron and folic acid during pregnancy can significantly reduce early neonatal deaths. It is noteworthy that one-fourth of newborn deaths are attributable to birth defects. Thus, it is worthwhile to investigate whether iron supplement can reduce the risk of CHD.

This community-based randomized controlled trial will assess and compare the impact of daily oral supplements of vitamin B complex along with folic acid or supplements of iron plus folic acid vs. folic acid alone given to women during peri-conception on CHD. It will also assess the effects of the three different supplementations on other pregnancy outcomes and maternal health. The study will be conducted in three rural poor counties including Xunyi, Changwu, and Bin, which are located in Shaanxi Province of Northwest China. All participants will sign informed consent before the study. The investigators hypothesize that the newborn infants of women receiving supplements of vitamin B complex along with folic acid or supplements of iron plus folic acid will experience a reduction in the prevalence of infants with the pulse oxygen saturation less than 95% and other adverse pregnancy outcomes compared with those receiving folic acid alone. The results of this trial will provide evidence needed to formulate policy on maternal micronutrient supplementation during peri-conception and the rationale for the necessary investment of public funds to implement appropriate programs against birth defects.

Eligibility criteria: Inclusion Criteria:

1. Women of reproductive age (15-49 years) who reside in the study areas;
2. Women who are prepared for pregnancy in 1-3 months or have already been pregnant for less than 20 months;
3. Women who have provided written informed consent.

Exclusion Criteria:

1. Women who have already taken supplements containing vitamin B complex, iron, or folic acid for more than two weeks at enrollment;
2. Women who have given birth to children with congenital heart disease or other birth defects before;
3. Women with diabetes;
4. women with severe heart, liver or kidney disease.

Primary outcomes:
measure: Neonatal pulse oximetry oxygen saturation measured by pulse oximetry
timeFrame: 6-72 hours after delivery
Secondary outcomes:
measure: Incidence of congenital heart disease and the subtypes
timeFrame: Half a year after delivery
measure: Incidence of birth defects and the subtypes
timeFrame: Half a year after delivery
measure: Birth weight measured by baby scale
timeFrame: Within 1 hours of delivery
measure: Incidence of low birth weight
timeFrame: Within 1 hour of delivery
measure: Gestational age at birth
timeFrame: At delivery
measure: Incidence of preterm birth
timeFrame: At delivery
measure: Incidence of perinatal mortality
timeFrame: Between 28 weeks of gestational duration and 7 days after delivery
measure: Incidence of stillbirth
timeFrame: At delivery
measure: Incidence of neonatal mortality
timeFrame: First 28 days after birth
measure: Incidence of early neonatal mortality
timeFrame: First 7 days after birth
measure: Incidence of pregnancy complications: hypertension, preeclampsia, antepartum haemorrhage, and infections
timeFrame: After enrollment until at delivery
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xi'an Jiaotong University College of Medicine
state: Shaanxi
Study officials:
affiliation: Xi'an Jiaotong University
name: Hong Yan, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mi B, Wen X, Li S, Liu D, Lei F, Liu R, Shen Y, Chen Y, Zeng L, Liu X, Dang S, Yan H. Vegetable dietary pattern associated with low risk of preeclampsia possibly through reducing proteinuria. Pregnancy Hypertens. 2019 Apr;16:131-138. doi: 10.1016/j.preghy.2019.04.001. Epub 2019 Apr 8.