Antioxidant Supplementation in Pregnant Women (ASIP1)

Antioxidant Supplementation in Pregnant Women With Low Antioxidant Status

The purpose of this study is to investigate the benefit of several micro nutrients of antioxidants (using milk) in a cohort of women with low antioxidant status and the changes in cell-free mRNA.

Study Overview

• Status: Completed
• Conditions: Pregnant Women; Preeclampsia
• Intervention / Treatment: Dietary supplement: micronutrient antioxidant; Dietary supplement: Control

Detailed Description

Preeclampsia remains one of leading causes of maternal and perinatal mortality and morbidity. Despite intensive research, the cause of preeclampsia has not been established. One of the theories is exaggeration of systemic inflammatory that might induce reactive oxygen species (ROS). It has been proposed that pregnancy will progress uneventfully if adequate antioxidant exists to buffer ROS. The ROS can induce endothelial dysfunction which leads to clinical symptoms of hypertension and proteinuria in preeclampsia. Several large randomized clinical trials of antioxidant supplementation have concluded that there were no benefits of antioxidants supplementation for prevention of preeclampsia. However, there is limited information about benefits of antioxidants in women with low antioxidant status at early gestation that deprived of the antioxidant most. Our aim, therefore, in this study was to assess whether early supplementation with milk enriched with vitamin and mineral, such as Cu, Zn, Mn, Fe, carotene, vitamin B6, B12, C, E, selenium, and calcium lowers the risk of preeclampsia in women with low antioxidant status at early gestation.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 13210
    • Cipto Mangunkusumo National Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women with 8-12 weeks of gestation

Exclusion Criteria:

• known multiple pregnancy
• known fetal anomaly
• known thrombophilia
• known infections and mola hydatidosa
• chronic renal failure
• uncontrolled hypertension
• known placental abnormalities
• documented uterine bleeding within a week of screening
• uterine malformation
• history of medical and metabolic complication such as heart disease or diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control	Dietary supplement: Control; supplementation with milk
Active Comparator: micronutrient antioxidant; Supplementation with milk enriched with vitamin and mineral, such as Cu, Zn, Mn, Fe, carotene, vitamin B6, B12, C, E, selenium, and calcium	Dietary supplement: micronutrient antioxidant; Supplementation with milk enriched with vitamin and mineral, such as Cu, Zn, Mn, Fe, carotene, vitamin B6, B12, C, E, selenium, and calcium; Other Names: antioxidant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preeclampsia	Preeclampsia was defined as gestational hypertension (systolic pressure ≥140 mmHg or diastolic blood pressure ≥ 90 mmHg [Korotkoff V] on ≥ 2 occasions after 20 weeks gestation) with proteinuria (> 0.3 g/day). Severe preeclampsia was defined by the presence of >1 of the following: (a) severe gestational hypertension (systolic pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg on 2 occasions after gestational week 20), or (b) severe proteinuria (≥5g protein in a 24-h urine specimen or ≥3 g in 2 random urine samples collected ≥4 h apart)	40 weeks
Preeclampsia	Preeclampsia was defined as gestational hypertension (systolic pressure ≥140 mmHg or diastolic blood pressure ≥ 90 mmHg [Korotkoff V] on ≥ 2 occasions after 20 weeks gestation) with proteinuria (> 0.3 g/day). Severe preeclampsia was defined by the presence of >1 of the following: (a) severe gestational hypertension (systolic pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg on 2 occasions after gestational week 20), or (b) severe proteinuria (≥5g protein in a 24-h urine specimen or ≥3 g in 2 random urine samples collected ≥4 h apart)	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell-free mRNA	Secondary outcome were level of mRNA level of angiogenic factors (vascular endothelial growth factor receptor-1 (VEGFR-1), placental growth factor (PlGF) and endoglin(ENG)); antioxidant status (FRAP, heme oksigenase-1 (HO-1) and superoxide-dismutase (SOD))	40 weeks

Collaborators and Investigators

• Sponsor: Showa University
• Collaborators: Indonesia University
• Investigators: Study Director: Noroyono Wibowo, MD, PhD, Dept Obstetrics Gynecology, Indonesia University; Principal Investigator: Yuditiya Purwosunu, MD, Dept Obstetrics Gynecology Indonesia University

Publications and helpful links

General Publications

• Wibowo N, Purwosunu Y, Sekizawa A, Farina A, Idriansyah L, Fitriana I. Antioxidant supplementation in pregnant women with low antioxidant status. J Obstet Gynaecol Res. 2012 Sep;38(9):1152-61. doi: 10.1111/j.1447-0756.2012.01855.x. Epub 2012 May 8.

Study record dates

Study Major Dates

• Study Start: June 1, 2001
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: November 1, 2010
• First Submitted That Met QC Criteria: November 1, 2010
• First Posted (Estimate): November 2, 2010

Study Record Updates

• Last Update Posted (Estimate): December 2, 2010
• Last Update Submitted That Met QC Criteria: November 2, 2010
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: preeclampsia; antioxidant supplementation
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Trace Elements; Antioxidants
• Other Study ID Numbers: asip02