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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Fetal Body Size, Fetal Brain Size

Intervention / Treatment
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* Dietary Supplement: Folic Acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Folic acid, Fetal body size, Fetal brain size