Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05859126 |
| Other study ID # |
IRB0147236 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 23, 2023 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
February 2024 |
| Source |
Cornell University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this 13-year follow up of a randomized control trial is to study the effect of
maternal choline supplementation on offspring cognition in adolescence.
The main question[s] it aims to answer are:
Does a higher dose of maternal choline choline (930 mg/d day supplementation) lead to
improved cognition in adolescence including hippocampal-dependent episodic memory and
executive functioning when compared to lower dose supplementation (480 mg/d).
In this follow-up of a clinical trial participants will complete online cognition testing and
emotion testing.
Description:
Eggs are one of the richest dietary sources of choline, an essential nutrient that plays
critical roles in fetal development, including shaping the structure and function of the
offspring brain. Furthermore, evidence shows that pregnancy dramatically increases the demand
for choline.
In rodents consuming standard chow, pregnancy results in a pronounced depletion of maternal
choline pools, indicating that choline requirements during pregnancy are increased and that
maternal and fetal requirements likely exceed the amount typically consumed by mothers.
Additionally, human research from the investigators' laboratory has found that the "Adequate
Intake" (AI) levels for choline during pregnancy, set in 1998 and based on the amount needed
to prevent liver damage in adult men, may not be sufficient to meet the demands of pregnancy.
Specifically, pregnant women consuming choline at the AI level have significantly lower
circulating concentrations of several choline metabolites compared to non-pregnant women, and
even doubling maternal choline intake (to twice the AI) fails to produce the metabolite
levels observed in non-pregnant women. Perhaps most importantly, a substantial body of
experimental research in animal models demonstrates that supplementation with additional
choline during pregnancy significantly improves lifelong memory, attention, and emotional
regulation in offspring, re-duces or eliminates normal ageing-related decline in cognitive
function, and reduces the im-pact of a range of prenatal neural insults (e.g., alcohol
exposure, maternal stress).
Despite extensive experimental data in animal models demonstrating lasting beneficial effects
of maternal choline supplementation on offspring memory, attention, and affect, few studies
have evaluated the effects of increasing maternal choline intake in humans. Moreover, results
from existing human studies are not sufficiently conclusive to alter dietary intake
recommendations for pregnancy. However, a randomized choline feeding trial from the
investigators' laboratory demonstrated beneficial effects of increased maternal choline
intake (930 mg/d vs. 480 mg/d) on offspring cognitive functioning during infancy and at 7
years of age (work supported in part by previous ENC funding). Based on these findings, the
investigators propose to follow up children born to mothers participating in this trial, to
examine longer-term effects of maternal choline supple-mentation on child cognition and
emotional well-being at thirteen years of age. This will be the first randomized controlled
trial (RCT) following children into adolescence, a time when tests are highly predictive of
adult functioning.
Choline is an essential nutrient that plays critical roles in fetal neurodevelopment. The
demand for choline increases markedly during pregnancy, indicated by a pronounced depletion
of maternal choline pools even when women consume the Adequate Intake (AI) level. It is a
concern that fewer than 10% of reproductive age women achieve the recommended AI level, and
that choline is not included in standard prenatal vitamin regimens.
Decades of rodent studies show that maternal choline intake affects offspring brain
structure, neural function and cognitive performance throughout life the lifespan. Maternal
choline deficiency produces lasting offspring cognitive impairment, whereas increasing
maternal choline intake markedly improves offspring cognition and provides widespread
neuroprotection in various diseases and early insults.
Only 3 Randomized Controlled Trials (RCTs) have evaluated offspring cognition following
maternal choline supplementation (MCS) in healthy human pregnancies. One trial conducted in
the investigators' lab demonstrated that MCS improves offspring cognition during infancy and
early childhood, but no studies have yet determined whether the beneficial effects observed
in the immature human brain are maintained in adulthood. This question can be addressed by
assessing the cognitive performance of MCS offspring in adolescence, a time when many
neurocognitive tests are strong predictors of ultimate adult functioning.
The planned study will take advantage of the unique opportunity to follow up the offspring of
women who participated in a controlled feeding study comparing two levels of choline intake
during pregnancy: 480 vs 930 mg/d. The offspring will be tested at 13 years old, an age when
cognitive functioning predicts adult functioning. The investigators predict that the
cognitive performance of the children born to women consuming 480 mg/d (approximately the AI)
during the last trimester of pregnancy will be poorer than children born to women consuming
930 mg/d.
The predicted results would strongly indicate that the low choline intake of most pregnant
women impedes the lifelong cognitive functioning of their children. Demonstrating this effect
would spur the addition of choline to standard prenatal vitamin regimens-the predicted result
being population-wide improvements in cognitive functioning, in part due to widespread
neuroprotection. These effects would be particularly beneficial for at-risk pregnancies and
underserved populations.
