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The Role of Nutrition in Fetal Alcohol
Spectrum Disorders (FASD)
Christina Chambers, PhD, MPH
University of California San Diego
International Conference on FASD – Krakow, Poland
October 1, 2015
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Nutrition and FASD
In
Nutritional status may lead to a
maternal-fetal environment in
which the effect of prenatal alcohol
is either amplified or reduced
In
alcohol-exposed pregnancies
children with FASD
Nutritional status may modify
cognitive, behavior or growth
abnormalities
Keen CL et al, Biofactors, 2010
+
What is the evidence that maternal
nutrition is important in FASD?
+ Maternal iron deficiency exacerbates
the effect of prenatal alcohol on conditioned
responses in rat pups
Rufer et al, PLOS One, 2012
+ Prenatal choline supplementation reduces learning
and growth deficits caused by prenatal alcohol in an
rat model
Thomas et al, Neurotox and Teratol, 2009
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Choline targets
Choline supplementation may be
targeting hippocampus which is
important for learning and memory
Choline may be targeting prefrontal
cortex which is important for executive
functioning (attention, working memory,
behavioral flexibility and regulation)
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Less adequate dietary intake in mothers
of children with FASD in South Africa
Nutrient
Mothers
FASD
N=43
%
<EAR
Mothers
No FASD
N=85
%
<EAR
P-value
Riboflavin
0.97 (0.31)
86%
1.16 (0.63)
62%
0.02
Calcium
305 (83)
100%
392 (187)
94%
<0.001
Choline
239.4 (82.0)
---
271.1 (140.7)
---
0.05
DPA
0.006 (0.01)
---
0.014 (0.03)
---
0.02
May et al, Reproduc Toxicol, 2014
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What is the evidence that nutrition is
important in children with FASD?
+ Postnatal supplementation ameliorates effects
of prenatal alcohol in animal models
Omega-3
supplements restore glutathione levels in
the brain and prevent oxidative damage
Vit
D3 supplementation reduces perseverative
behavior
Choline
supplementation dampens effects on spatial
learning, working memory, reversal learning, and
open field hyperactivity
Patten et al, Neuroscience
J Nutr Biochem,
2013 2013
Letters,
Idrus et al, J Steroid Biochem Molec Biol, 2013
Thomas et al, various
+ Iron deficiency in infants exacerbates
effects of alcohol dose on growth at
5 years of age
Carter et al, Alc Clin Exper Res, 2012
+
Vitamin supplements as an
intervention for FASD in humans
Examples
of two trials recently completed that
tested vitamin supplement interventions – one in
pregnancy and one in children
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Ukraine clinical study
To
assess the effectiveness of a
vitamin/mineral supplement
intervention in pregnancy on
neurodevelopment of alcohol-exposed
infants
+
Rivne Diagnostic Center team
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Khmelnytsky Perinatal Center
team
Enrolled
pregnant women who reported
frequent binge drinking in pregnancy and
pregnant women with no or low alcohol
consumption
Blood
samples collected for nutrition
measures
Randomized
women to a multivitamin/mineral
supplement with or without additional 750 mg.
choline
“No intervention” arm received standard of
care advice to take prenatal vitamins
Bayley
Scales of Infant Development II
Information
processing measured using
cardiac orienting response (COR)
habituation/dishabituation
auditory or visual stimulus
following an
+
Neurobehavioral testing
+ Information processing cardiac
orienting response
+
Bayley Scales of Infant
Development
163
in the alcohol exposed group
evaluated at 6 months of age
204
in the low/unexposed group
evaluated at 6 months of age
+ Psychomotor Developmental Index at 6
months of age
Alcohol p <0.04; MVM – NS
Coles et al, Matern Child Health J, 2015
+ Mental Developmental Index at 6
months of age
Alcohol dose p <0.001
Coles et al, Matern Child Health J, 2015
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Bayley Scales of Infant
Development
No
additional benefit of choline
supplementation
+
Information Processing COR
77
in the alcohol exposed group
evaluated at 6-12 months of age
91
in the low/unexposed group
evaluated at 6-12 months of age
Kable et al, Alcohol 2015 in press
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Information Processing COR
Choline
supplementation resulted in
better performance in both alcohol
exposed and unexposed infants
Greater
change in heart rate in visual
habituation trials (p<0.001)
Improved speed of response
Kable et al, Alcohol 2015 in press
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Information Processing COR
Improvement
in maternal choline blood level
over the course of pregnancy was
associated with better performance
There
was no evidence of a benefit of
multivitamin mineral supplementation on this
measure
Kable et al, Alcohol 2015 in press
Postnatal intervention trial
Tanya Nguyen, PhD
Postnatal choline supplement trial
55
children ages 5-10 years with confirmed
histories of heavy prenatal alcohol exposure
Randomized
to receive choline supplements or
placebo for a 6 week period
Pre
and post-test using a standard neurobehavioral
testing battery, assessment of dietary intake
9
Delayed Matching to Sample
8
Number Correct
Memory
7
6
5
4
3
2
1
Pattern Recognition Memory
0
20
Pre-test
Paired Associates Learning
10
60
5
0
Pre-test
Placebo: d = -.21
■ Choline: d = .03
Post-test
Total Errors (Adjusted)
Number Correct
15
Post-test
Placebo: d = .00
■ Choline: d = -.14
50
40
30
20
10
0
Pre-test
Post-test
Placebo: d = -.25
■ Choline: d = -.17
Spatial Span
4,5
4
Span Length
Executive function
3,5
3
2,5
2
1,5
1
0,5
70
0
Spatial Working Memory
Pre-test
50
40
45
30
Spatial Working Memory
40
20
35
10
0
Pre-test
Placebo: d = -.25
■ Choline: d = -.12
Post-test
Strategy Score
Total Errors
60
Post-test
Placebo: d = .06
■ Choline: d = -.07
30
25
20
15
10
5
0
Pre-test
Post-test
Placebo: d = -.16
■ Choline: d = .36
Dietary choline
Regardless of group, higher levels of dietary choline may be related to
better memory performance at post-test, after controlling for pre-test
performance
Delayed Matching to Sample @ Post-test
16
Choline
14
Placebo
12
Number Correct
10
8
6
4
2
0
0
100
200
300
400
Daily Dietary Choline Intake (mg)
500
Considerations – both trials
Duration,
dose, timing of treatment (trimester? age
of child?)
Genetic
susceptibility
polymorphisms
in PEMT, MTHFD1 and choline
dehydrogenase may relate to higher dietary
requirement for choline
+
Nutrition and growth in children with
FASD: Growth deficiency or
obesity?
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Dietary intake in children with
prenatal alcohol exposure/FASD
31
children with an FASD, 2.5-4.9 years of
age
Children with an FASD had significantly
lower intakes of saturated fats, Vitamin D
and calcium compared to NHANES
Fugelstad et al, Neurotox and Teratol, 2013
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Dietary intake in children with
prenatal alcohol exposure/FASD
19
children with prenatal alcohol exposure, mean
age 9.6 years
50% of girls overweight/obese; 37% of boys had
reduced stature, weight or BMI for age
More than 50% had dietary intakes <RDA/AI for
choline, Vitamin E, potassium, B-carotene, Vitamin
D, and essential fatty acids
Werts et al, Alc Clin Exper Res, 2014
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Overweight/obesity in children with
FASD
Increased
rates of overweight or
obesity seen in 445 children with
FASD, particularly in adolescent
females
Fugelstad et al, Alc Clin Exp Res, 2014
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Follow-up of children in Ukraine
Following
children in the cohort to 5 years
of age
neurobehavior
growth
eating
behavior
nutrition
+
+
Eating behaviors in 4 year old
children
Unexposed
N = 50
Exposed
N = 33
P-value
Food Resp
Enjoy Food
Satiety
2.0 (0.6)
3.3 (0.7)
3.2 (0.6)
2.3 (0.5)
3.3 (0.7)
3.2 (0.5)
0.002
0.996
0.855
Slow
Eating
Emotional
Eating
Fussy
Eating
2.6 (1.0)
3.0 (0.9)
0.052
2.3 (1.0)
2.8 (1.2)
0.100
3.0 (0.8)
2.9 (0.9)
0.627
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Eating behaviors in 4 year old
females
Food Resp
Emotional
Eating
Unexposed
N = 19
Exposed
N = 15
P-value
1.8 (0.6)
2.1 (0.9)
2.6 (0.6)
3.1 (1.1)
0.002
0.008
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Eating behavior and growth
Postnatal
BMI Z scores collected at 2-5 time
points from 1 month to 4 years of age
Correlations
between eating behaviors and
growth trajectory compared within alcohol
exposure groups
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+
+
Summary
Iron
deficiency in mother and infant may
exacerbate the effects of prenatal alcohol
Multivitamin/mineral
and choline
supplements given during an alcoholexposed pregnancies were beneficial for
infants on some measures of performance
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Summary
Choline
supplements given over a 6 week
period to school age children with FASD did
not show benefit on neurobehavioral
measures
Dose,
timing, duration, age of child, genetic
susceptibility and dietary intake of choline
may be important
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Summary: eating behavior and
growth
Some
evidence that children with FASD have
altered dietary intakes
Eating
behavior up to 4 years of age is
associated with BMI trajectory in alcoholexposed children
Are
children with FASD at increased risk for
becoming overweight?
If yes, is this mediated by altered eating
behaviors?
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Much more to be learned!
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Thanks to collaborators and funders
NIH-NIAAA and the Office of Dietary Supplements
Lyuba Yevtushok, MD – Rivne Diagnostic Center
Natalya Zymak, MD – Khmelnystky Perinatal Center
Ken Jones, MD – UCSD
Kerri Boutelle, PhD - UCSD
Carl Keen, PhD – UC Davis
Jan Uriu-Adams, PhD – UC Davis
Claire Coles, PhD – Emory University
Julie Kable, PhD – Emory University
Wladimir Wertelecki, MD – University of South Alabama/UCSD
Tanya Nguyen, PhD - SDSU
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Thank you!
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