Preventing Fetal Body and Brain Size Reduction in Low-income Smoking Mothers: A Randomized Clinical Trial

The purpose of this study is to find out if folic acid prevents of the reduction of fetal body and brain size in infants whose mothers smoke.

Study Overview

• Status: Completed
• Conditions: Fetal Body Size; Fetal Brain Size
• Intervention / Treatment: Dietary supplement: Folic Acid

Detailed Description

Smoking during pregnancy remains a common practice despite smoking cessation programs offered to mothers. Only 20-40% of women quit smoking during pregnancy which implies that a majority of smokers continue smoking despite the associated feto-infant morbidity and mortality. It is therefore important to identify ways and means of protecting these infants as they grow and develop during intrauterine life. In this study, we propose to assess the utility of higher-strength folic acid (4mg) combined with smoking cessation programs as compared to standard of care (smoking cessation program and low-strength (0.8mg) folic acid) in reducing the level of morbidity (specifically fetal body and brain size) sustained by infants of smokers

• Study Type: Interventional
• Enrollment (Actual): 495
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida, College of Public Health, Department of Epidemiology and Biostatistics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 44 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

((1) Smoker, based on presence of detectable cotinine in saliva (biomarker).; (2) Ages 18-44 years; (3) Singleton gestation (< 20 weeks), confirmed by sonogram; (4) Residents of Tampa, Florida or surrounding area in order to facilitate follow-up and reduce attrition rate.

Exclusion Criteria:

(a) an indication for chronic blood transfusion. Women receiving chronic blood transfusions will not be enrolled, as transfused red blood cells (RBC) can result in inaccurate analysis of folate RBC levels88; (b) generalized seizure disorder treated with anti-convulsant medication: Patients with generalized seizure disorder treated with anticonvulsant medication will be excluded because of the potential association with folic acid deficiency88.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Higher-strength folic acid; Higher-strength folic acid (4mg).	Dietary supplement: Folic Acid; 4mg of higher strength folic acid once a day until delivery
No Intervention: Low-strength folic acid; Low-strength (0.8mg) folic acid (standard of care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal Body Size	Low birth weight will be defined as birth weight less than 2500g; Small for gestational age will be defined as birth weight in the lowest 10th percentile; The fetal growth ratio will be expressed as the ratio of the observed birth weight to the expected mean birth weight for each gestational age.	Participants will be followed from baseline (first trimester) until delivery
Fetal Brain Size	Head Circumference at birth: will be measured at birth as routinely performed at the study site. Observed: Expected head circumference ratio: This is the ratio between the actual head circumference and the expected head circumference according to gestational age (this could also be expressed in terms of percentage of expected head circumference). Brain weight: will be estimated from formula: brain weight (g) = 0.037 X head circumference (cm)2.57. Brain-to-body ratio (BBR): The BBR is defined as 100 the ratio of the infant's estimated brain weight to its birth weight.	Participants will be followed from baseline (first trimester) until delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm Birth	This is defined as live birth after 20 weeks of gestation but before 37 completed weeks. Genetic and Epigenetic Markers of Fetal Brain Growth and Development: Cord blood obtained at delivery will be analyzed for selected regulatory genes.	Participants will be followed from baseline (first trimester) until delivery

Collaborators and Investigators

• Sponsor: Hamisu Salihu
• Investigators: Principal Investigator: Hamisu M Salihu, MD, PhD, University of South Florida

Publications and helpful links

General Publications

• Yusuf KK, Salihu HM, Wilson R, Mbah A, Sappenfield W, Bruder K, Wudil UJ, Aliyu MH. Folic Acid Intake, Fetal Brain Growth, and Maternal Smoking in Pregnancy: A Randomized Controlled Trial. Curr Dev Nutr. 2019 Apr 4;3(6):nzz025. doi: 10.1093/cdn/nzz025. eCollection 2019 Jun.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: November 10, 2010
• First Submitted That Met QC Criteria: November 23, 2010
• First Posted (Estimate): November 25, 2010

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Folic acid; Fetal body size; Fetal brain size
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid
• Other Study ID Numbers: 1KG14