BMI-based Vitamins in Obese Pregnant Women

BMI-Based Prenatal Vitamins to Ameliorate Oxidative Stress in Obese Pregnancy

The purpose of this study is to devise and pilot a BMI-based prenatal vitamin for obese pregnant women. Currently, all pregnant women, regardless of body mass index, take the same prenatal vitamin. The investigators have found that obese pregnant women have higher levels of inflammation and oxidative stress, and a concomitant depletion of specific antioxidant micronutrients. The investigators have also found, in an animal model, that decreasing inflammation and oxidative stress during obese pregnancy was associated with improved offspring outcomes. Here the investigators aim to understand whether a BMI-based prenatal vitamin is effective in decreasing markers of inflammation and oxidative stress by raising concentrations of antioxidant micronutrients and in pregnancies complicated by obesity.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Dietary supplement: BMI-based prenatal vitamin; Dietary supplement: Standard prenatal vitamin

Detailed Description

The investigators' central hypothesis is that pregnancy in obese women creates an oxidant/anti-oxidant imbalance, which adversely impacts maternal health and neonatal outcome. The investigators hypothesize that restoring oxidant/anti-oxidant balance with a body mass index (BMI) based prenatal micronutrient supplement will decrease oxidative stress. The investigators aim to devise a prenatal vitamin supplement based on maternal BMI to increase serum levels of antioxidant vitamins in obese pregnancy, to assess how the BMI-based prenatal vitamin supplementation impacts markers of oxidative stress and inflammation in obese pregnant women and to evaluate the effectiveness of this vitamin formulation in reducing oxidative stress and inflammation and improving growth trajectories in infants born to obese women.

The investigators will conduct a double-blind randomized-controlled study. Two groups of women will be randomized independently. 1) Obese women (BMI>30) planning pregnancy through the through advertising and mailings (N=50) and 2) Pregnant women who are early in pregnancy (<13 weeks) will be approached at their first prenatal visit at the BWH and BIDMC obstetric practices (N=120).

Women will be prescreened and approached by study staff if they qualify. After informed consent is obtained, patients will be randomized to either control or intervention group by computer-generated permuted block randomization. All subjects will be given a standard prenatal vitamin provided by the study and in addition, the control group will be given a placebo and the Intervention group will be given a supplement with vitamin C, E, B6 and folate.

The outcomes are maternal systemic markers inflammation and oxidative stress and micronutrients. At the time points mentioned above, the following laboratory assays will be conducted in maternal blood or urine: C reactive protein, vitamins C, E, B6, folate 8-iso-PGF2a and 8-OHdG. The secondary outcomes are cord blood markers of inflammation and oxidative stress, breastfeeding outcomes, and the following infant outcomes over the first year: neurodevelopmental outcome, growth trajectories and adiposity, systemic markers of inflammation and oxidative stress.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pre-pregnancy weight or early first trimester weight (BMI > or equal to 30 kg/m2)
• Women can be either planning pregnancy (who are trying to conceive or will be trying to conceive in the coming 6 months) or <14 weeks pregnant

Exclusion Criteria:

• More than two first trimester pregnancy losses
• History of delivering an infant with a major congenital anomaly
• Pre-existing diabetes
• Autoimmune disease such as lupus
• Chronic inflammatory condition such as rheumatoid arthritis
• Uncontrolled stage two or three hypertension at baseline (systolic>160 or diastolic>100 mmHg)
• On anticoagulant therapy
• History of cigarette smoking within the past 12 months
• Lactose intolerant
• Vegan
• Unwilling to stop taking their current supplements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Investigative; This arm receives a standard prenatal (provided by the study) and a micronutrient supplement.	Dietary supplement: BMI-based prenatal vitamin; The intervention group receives additional antioxidant micronutrients that we have found to be decreased in obese pregnant women.
ACTIVE_COMPARATOR: Control; Standard prenatal vitamin provided by the study	Dietary supplement: Standard prenatal vitamin; Standard prenatal vitamin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal systemic marker of inflammation	Serum C Reactive Protein	35-40 weeks of pregnancy
Maternal systemic marker of oxidative stress	Urinary 8-Oh-dG	35-40 weeks of pregnancy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal antioxidant vitamins	Plasma Vitamin C	35-40 weeks of pregnancy
Maternal antioxidant vitamins	Serum Vitamin B6	35-40 weeks of pregnancy
Maternal antioxidant vitamins	Serum Vitamin E	35-40 weeks of pregnancy
Maternal antioxidant vitamins	Serum and Red Blood Cell folate	35-40 weeks of pregnancy
Cord blood marker of inflammation	Serum C Reactive Protein	Delivery
Cord blood markers of oxidative stress	8-epi-PGF2 alpha	Delivery
Breastfeeding intensity	Complete questionnaire on infant feeding	two, six and twelve months postpartum
Infant weight	Measure infant weight (kg)	birth, 6 months and one year
Infant length	length (cm) measured using a length board	birth, six months and one year
Infant head circumference	head circumference (cm) will be measured using tape measure technique	birth, six months and one year
Infant adiposity	adiposity by peapod measurement at birth and by skin fold thickness at birth, six months and one year	birth, six months and one year
Infant marker of inflammation	Serum C Reactive Protein	1 year

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: SARBATTAMA SEN, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Sen S, Simmons RA. Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats. Diabetes. 2010 Dec;59(12):3058-65. doi: 10.2337/db10-0301. Epub 2010 Sep 7.
• Sen S, Iyer C, Meydani SN. Obesity during pregnancy alters maternal oxidant balance and micronutrient status. J Perinatol. 2014 Feb;34(2):105-11. doi: 10.1038/jp.2013.153. Epub 2013 Dec 19.
• Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Hebert JR, Sen S. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol. 2016 Apr;36(4):284-90. doi: 10.1038/jp.2015.199. Epub 2016 Jan 7.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ACTUAL): September 1, 2017
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (ESTIMATE): June 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Maternal Obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Micronutrients; Vitamins
• Other Study ID Numbers: 2014P001393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Non-PHI, deidentified IPD will be shared with requesting investigators. A limited data set, generated based on variables identified in an analysis plan approved by PNV investigators, will be sent via secure email or shared dropbox to requesting investigators.
• IPD Sharing Time Frame: Data will be shared after publication of primary outcomes manuscript for a period of ten years.
• IPD Sharing Access Criteria: Investigators requesting access will be asked to submit a proposal and analysis plan to analyze the requested data, including plans for dissemination and authorship.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE