Effects of Prenatal DHA Supplements on Infant Development

Study Overview
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Brief Summary
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This research study research is about the significance of polyunsaturated fatty acids (PUFAs) for human development. Specifically, the study team will assess the effect of docosahexanoic acid (DHA) supplementation during pregnancy on infant growth and development through a randomized controlled intervention trial in Cuernavaca, Mexico. This is a collaborative effort between the Rollins School of Public Health, Emory University, the Instituto Nacional de Salud Publica (INSP) and the Instituto Mexicano del Seguro Social (IMSS), Cuernavaca, Mexico. Pregnant women attending the IMSS General Hospital I are recruited between 18-22 weeks gestation and assigned randomly to receive either DHA (400 mg) or a placebo daily until delivery. The main study outcomes include a) birth outcomes: birth size, gestational age, cord blood levels of DHA and neurodevelopment b) maternal blood and breast milk DHA levels at 1 and 3 months post-partum, c) postnatal growth and development during the first 5 years of age and d) infant DHA status at 3, 12 and 18 months.

Detailed Description
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This research study is about the significance of polyunsaturated fatty acids (PUFAs) for human development. Specifically, the study team will assess the effect of docosahexanoic acid (DHA) supplementation during pregnancy on infant growth and development through a randomized controlled intervention trial in Cuernavaca, Mexico. This is a collaborative effort between the Rollins School of Public Health, Emory University, the Instituto Nacional de Salud Publica (INSP) and the Instituto Mexicano del Seguro Social (IMSS), Cuernavaca, Mexico. Pregnant women attending the IMSS General Hospital I are recruited between 18-22 wks gestation and assigned randomly to receive either DHA (400 mg) or a placebo daily until delivery. The main study outcomes include a) birth outcomes: birth size, gestational age, cord blood levels of DHA and neurodevelopment b) maternal blood and breast milk DHA levels at 1 and 3 mo post-partum c) postnatal growth and development during the first 5 years of age and d) infant DHA status at 3, 12 and 18 mo. All data collection is carried out at the study headquarters (IMSS) except for home environment that is assessed during home visits. Physical growth (length, weight, and head circumference) and infant and child development (visual and auditory evoked potentials, visual attention, Bayley scales of infant development, McCarthy child development score, Hearts and Flowers stroop test, and other computerized child development tests) are measured at birth, 1, 3, 6, 9, 12, 18, 24, 36 months and at 4 and 5 years of age by trained workers. Data are also obtained on socioeconomic status, obstetric history, maternal diet, anthropometry and intelligence, quality of home environment and infant feeding practices. Data analysis will include group comparisons (intent-to-treat) after ensuring effectiveness of randomization, and structural equation modeling to examine the various pathways by which DHA supplementation during pregnancy affects child growth and development. The findings of this project will contribute significantly to our understanding of the functional consequences of DHA supplementation during pregnancy.

Official Title
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Effects of Prenatal DHA Supplements on Infant Development

Conditions
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Pregnancy

Intervention / Treatment
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* Dietary Supplement: DHA
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-22 weeks pregnant (based on last menstrual period) 18 - 35 years old Resident of Cuernavaca who intends to deliver at the IMSS General Hospital I and remain in the area for the 2 years following recruitment Intends to predominantly breastfeed infant until 3 months of age Agrees to participate with informed consent Exclusion criteria High risk pregnancy: If documented in the clinical record at recruitment and will include history and prevalence of abruptio placentae, any serious bleeding episode in the current pregnancy, gestational diabetes, pregnancy induced hypertension, maternal toxoplasmosis infection during pregnancy, coagulation disorders, thrombocytopenia or chronic vascular, renal or systemic disease and drug use. Lipid metabolism (hyperlipidemia) and/or absorption disorders Regular intake of fish oil or DHA supplements during pregnancy Chronic use of medication for illnesses like epilepsy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: DHA arm<br>Docosahexonic acid (DHA) (400 mg/day). Pregnant women attending the IMSS General Hospital I are recruited between 18-22 wks gestation and assigned randomly to receive either DHA (400 mg) or a placebo daily until delivery. | Dietary Supplement: DHA<br>* 400 mg/d of docosahexanoic acid (DHA) during pregnancy<br>* Other names: Martek Algal DHA;|
| Placebo Comparator: Placebo arm<br>Pregnant women attending the IMSS General Hospital I are recruited between 18-22 wks gestation and assigned randomly to receive either DHA (400 mg) or a placebo daily until delivery. | Dietary Supplement: Placebo<br>* 2 tablets daily during pregnancy<br>* Other names: Specially formulated by Martek Biosciences;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth size | Birth size will be determined by measuring the newborn, a baby's length is measured from the top of their head to the bottom of one of their heels. | Birth | 
| Gestational age | Gestational age is measured in weeks, from the first day of the woman's last menstrual cycle to the current date. | Birth | 
| Changes in visual evoked potentials | Visual evoked potential (VEP) is an electrical signal emanated from the brain while a visual stimulus is presented to the subject in a time locked manner. The VEP can be used as a diagnostic tool to detect ocular diseases in patients with visually impaired. VEP response can also be used to detect eye diseases like glaucoma, diabetic retinopathy, multiple sclerosis, ocular hypertension, loss of peripheral (side) vision, macular degeneration and color blindness. | 3 and 6 months of age | 
| Changes in infant weight | Infant weight is measured in kilograms (kg) and weight is measured in the hospital and at all check-ups. | Birth, months 1, 3, 6, 9, 12, 18, 24, 36 and at 4 and 5 years of age | 
| Changes in infant height | Infants will be measured in the hospital and at all check-ups. Height is measured in centimeters (cm). | Birth, months 1, 3, 6, 9, 12, 18, 24, 36 and at 4 and 5 years of age | 
| Changes In infant head circumference | Head circumference or OFC [occipital frontal circumference] is measured over the most prominent part on the back of the head (occiput) and just above the eyebrows (supraorbital ridges). This can be translated to mean the largest circumference of the head. Head circumference is measured in centimeters (cm). | Birth, months 1, 3, 6, 9, 12, 18, 24, 36 and at 4 and 5 years of age | 
| Changes in auditory evoked potentials | A brainstem auditory evoked response (BAER) test measures how the brain processes the sounds a person hears. The BAER test records the subject's brainwaves in response to clicks or other audio tones that are played for them. | 1 and 3 months of age | 
| Changes in child development score | The Bayley Scales of Infant Development -II are used to assess child development during the first two years of life while The McCarthy Scales of Children's Abilities (MSCA) is a psychological instrument for young children that measures cognitive ability in six domain areas: Verbal, Perceptual-Performance, Quantitative, General Cognitive, Memory, and Motor at age 5 y. | 1, 1.5 and 5 years of age | 
| Changes in Hearts and Flowers Stroop Test | This tests working memory, response inhibition, and task switching/cognitive flexibility . The task requires participants to press a response button that is either on the same side (congruent) or opposite side (incongruent) of an image. When children see an image of a heart, they are instructed to press the corresponding directional arrow button on a keyboard. When children see an image of a flower, they are instructed to press the opposite directional arrow button on the keyboard . The task consists of three separate levels that contain only congruent trials (12 trials total), only incongruent trials (12 trials total), and mixed congruent and incongruent trials respectively (33 trials total). Images are presented on a computer monitor. Before both the congruent and incongruent trial blocks, a training period is administered which consists of 5 trials. The child is unable to advance to the next question until they respond correctly. | 5 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes Immune function |  | first 6 months of life | 
| Changes in Morbidity | Changes in morbidity (health) factors will be assessed. | Birth, months 1, 3, 6, 9, 12, 18, 24, 36 and at 4 and 5 years of age | 
| Cognitive outcomes at age 7 years of age | The cognitive intelligence test WAIS-IV offers compound scores that reflect the intellectual functioning of 4 cognitive areas (verbal understanding, perceptive reasoning, working memory and processing speed). It also offers a compound score that reflects intellectual aptitude in general (Intelligence quotient). | At 7 year follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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birth size, gestational age, development, child growth,, prenatal nutrition, DHA