A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants

This study investigated whether adding specific long-chain polyunsaturated fatty acids (LCPUFAs) to infant formula could improve mental development in healthy term infants.

The **interventions** were two types of infant formula:

1. **DHA-supplemented formula:** Contained 0.35% docosahexaenoic acid (DHA).

2. **DHA+AA-supplemented formula:** Contained 0.36% DHA and 0.72% arachidonic acid (AA).

The **comparator** was a standard **control formula** that did not provide any DHA or AA.

The primary **outcome measures** for mental development were assessed using the Bayley Scales of Infant Development, 2nd edition (BSID-II) at 18 months of age. Specifically, the researchers focused on:

**Mental Development Index (MDI):** A broad measure of cognitive abilities, including memory, problem-solving, and early language skills.

**Psychomotor Development Index (PDI):** A measure of motor skills, such as gross and fine motor coordination.

**Behavior Rating Scale:** An assessment of the child's behavior during the test.

**Subscales of the MDI:** Cognitive, motor, and language subscales were also analyzed separately.

Additionally, earlier assessments at 4 months and 12 months of age included:

**Blood fatty-acid composition:** To confirm the infants were absorbing the supplemented DHA and AA.

**Sweep visual evoked potential (VEP) acuity:** A measure of visual processing speed and clarity.

**Forced-choice preferential looking (FPL) acuity:** Another measure of visual sharpness. While these were assessed, the abstract primarily reports on the 18-month BSID-II results.

The study included **56 healthy term infants** (26 male, 30 female).

**Population:** Healthy infants born at full term (not premature).

**Enrollment:** Infants were enrolled in the trial within the first 5 days of life. This early enrollment ensured that the dietary intervention began very early in development.

**Setting:** The children were tested at the Retina Foundation of the Southwest in Dallas, TX, suggesting a specialized research environment.

**Age at assessment:** The primary mental development assessment was conducted when the children were 18 months old. The dietary intervention itself lasted until 17 weeks of age.

The primary method for assessing mental development was the **Bayley Scales of Infant Development, 2nd edition (BSID-II)**. This is a widely recognized and standardized assessment tool used by developmental psychologists and pediatricians to evaluate the developmental functioning of infants and young children, typically from 1 to 42 months of age.

The BSID-II provides several key scores:

**Mental Development Index (MDI):** This is a composite score designed to assess cognitive abilities. It covers areas such as sensory perception, memory, problem-solving, early language, and concept formation. Scores are standardized with a mean of 100 and a standard deviation of 15, meaning a score of 100 is average for a child of that age. Higher scores indicate more advanced mental development.

**Psychomotor Development Index (PDI):** This index measures motor skills, including both gross motor skills (like sitting, crawling, walking) and fine motor skills (like grasping, manipulating objects). Like the MDI, it has a mean of 100 and a standard deviation of 15.

**Behavior Rating Scale:** This component assesses the child's behavior during the testing session, including aspects like attention, persistence, emotional regulation, and cooperation. It helps provide context for the MDI and PDI scores.

The researchers also looked at specific **subscales** of the MDI, including cognitive, motor, and language subscales, to pinpoint more granular effects.

Earlier in the study, at 4 months and 12 months, other measures were taken:

**Blood fatty-acid composition:** Blood samples were analyzed to measure the levels of DHA and AA in plasma and red blood cells. This was crucial to confirm that the dietary supplements were actually being absorbed and incorporated into the infants' bodies.

**Sweep visual evoked potential (VEP) acuity:** This is an objective measure of visual function. Electrodes placed on the scalp record brain activity in response to visual stimuli (like changing patterns on a screen). It assesses how well the visual system is processing information.

**Forced-choice preferential looking (FPL) acuity:** This is another method to assess visual acuity in infants who cannot verbally report what they see. Infants naturally prefer to look at more complex or patterned stimuli. By presenting an infant with a plain field and a patterned field, researchers can infer their visual acuity based on which field they prefer to look at.

For the purpose of this wiki page, the focus is primarily on the 18-month BSID-II results as highlighted in the abstract.

This study employed a **randomized controlled trial (RCT)** design, which is considered the gold standard for evaluating the effectiveness of interventions.

**How they ran the study:**

1. **Enrollment:** Healthy term infants were enrolled within the first 5 days of life. This early enrollment ensured that the dietary intervention began at a critical period of rapid brain development.

2. **Randomization:** Although not explicitly detailed in the abstract, the term "randomized clinical trial" implies that infants were randomly assigned to one of the three diet groups: DHA-supplemented formula, DHA+AA-supplemented formula, or control formula. Randomization is a crucial step where participants are assigned to different groups purely by chance. This helps to ensure that, on average, the groups are similar in all characteristics (known and unknown) at the start of the study, except for the intervention they receive. This minimizes the risk that any observed differences in outcomes are due to pre-existing differences between the groups rather than the intervention itself.

3. **Intervention Duration:** Infants were fed their assigned diet from enrollment (within 5 days of life) up to 17 weeks of age. This means the intervention lasted for approximately 4 months.

4. **Follow-up and Assessment:** After the intervention period, the children were followed up. Their blood fatty-acid composition, VEP acuity, and FPL acuity were assessed at 4 months and 12 months. The primary outcome, mental development, was assessed using the Bayley Scales of Infant Development, 2nd edition (BSID-II), when the children reached 18 months of age. This long-term follow-up allowed the researchers to see if early dietary changes had lasting effects.

5. **Blinding:** The abstract does not explicitly state whether the study was blinded. In infant formula studies, it is often challenging to blind the parents/caregivers to the type of formula their child is receiving, as formulas can differ in appearance, smell, or even how they are tolerated by the infant.