repeated neonatal oral sucrose treatment affects growth
TRANSCRIPT
Repeated Neonatal Oral Sucrose Treatment Affects Growth and Alters Insulin-Like Growth Factor-1 and Liver Choline Metabolism in Female Mice
Departments of Medicine1, Pediatrics2, Obstetrics and Gynecology3, Pathology4 , Nursing5, Psychology6, and Occupational Science and Occupational Therapy 8; University of British Columbia and British Columbia Children’s Hospital Research Institute.
Cynthia Yamilka Ramírez-Contreras 1, Alejandra M. Wiedeman 2, Ei-xia Mussai 3, Nicha Boonpattrawong 4, Arya Mehran2 ,Manon Ranger 5, Kiran Soma 6 Liisa Holsti 7, Angela M. Devlin2.
Background Results
AcknowledgementsHealthy StartsCatalyst Grant
• Premature infants (<37 weeks of gestation) often require hospitalization in the neonatal intensive care unit, where they experience painful procedures due to medical care.
• Oral sucrose is the non-pharmacological standard of care for minor procedural pain relief.1
• Approximately 0.5-2mL of a 24% sucrose solution is administered orally prior to each painful procedure.
• Infants can be exposed to high and cumulative volumes of sucrose.2
Concerns about neonatal sucrose treatment• Adult mice treated with neonatal sucrose have
reduced white and grey matter.3• Very preterm infants that received multiple doses of
sucrose have poorer attention and motor function.4
ObjectiveTo determine the long-term effects of repeated neonatal oral sucrose treatment on growth, glucose homeostasis and liver choline metabolites using an animal model.
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1.0
0.5
0.1
Methods
• Neonatal sucrose treatment affects growth in female, but not in male mice and may involve an IGF-1 and choline-dependent pathways.
Conclusions
1. Stevens et al. Cochrane Database Syst Rev 2016; 7:CD0010692. Holsti and Grunau. Pediatrics 2010;125:1042-10473. Tremblay et al. Pain 2017;158:1586-15984. Johnston et al. Pediatrics 2002;110;523-8
References
Growth
Data presented as mean ± SD. One-way ANOVA (Tukey post hoc analysis)
Serum IGF-1
** p<0.01, *p<0.05
Contact: [email protected]
Water Sucrose Fructose Glucose0
4
8
12
16
Nos
e/an
us
leng
th (c
m)
Water Sucrose Fructose Glucose0
4
8
12
16
Nos
e/an
us le
ngth
(cm
)
Water Sucrose Fructose Glucose0
6
12
18
Tibi
a le
ngth
(mm
)
✱✱ ✱✱
✱✱
p=0.001 p=0.003
p=0.001
Water (16.73 ± 0.2mm)Sucrose (16.07 ± 0.4 mm)Fructose (16.59 ± 0.28mm)Glucose (16.50 ± 0.22mm)
Water Sucrose Fructose Glucose0
6
12
18
Tibi
a le
ngth
(mm
)
Water Sucrose Fructose Glucose0
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Seru
m IG
F-1
(ng/
mL)
Water Sucrose Fructose Glucose0
200
400
600
800
1000
Seru
m IG
F-1
(ng/
mL)
✱
p=0.028
Figure 3.Liver water-soluble choline metabolites at 16 weeks
Figure 1. Body weight
Figure 2. Body size and serum IGF-1 at 16 weeks
Female
Postnatal day 1
Male
Postnatal day 7
0 3 6 9 12 15 18 210
5
10
15
Day
Bod
y w
eigh
t (g
)
Water
Sucrose
Fructose
Glucose
* p=0.001Sucrose vs AllRepeated Measures
✱ ✱
0 3 6 9 12 15 18 210
5
10
15
Day
Bod
y w
eigh
t (g
)
Water
Sucrose
Fructose
Glucose
* p=0.001Sucrose vs AllRepeated Measures
✱ ✱
Water Sucrose Fructose Glucose0
1
2
3
Bod
y w
eigh
t (g)
Water Sucrose Fructose Glucose0
1
2
3
4
5
Bod
y w
eigh
t (g)
✱✱✱✱
✱✱
Water Sucrose Fructose Glucose0
5
10
15
Bod
y w
eigh
t (g) ✱✱✱
p=0.007 p=0.020
Suckling period Weaning (3weeks)
Water Sucrose Fructose Glucose0
10
20
30
40
Bod
y w
eigh
t (g)
Adulthood (16 weeks)
Water Sucrose Fructose Glucose0
1
2
3
Bod
y w
eigh
t (g
)
Water Sucrose Fructose Glucose0
2
4
6
Bod
y w
eigh
t (g
)
0 3 6 9 12 15 18 210
5
10
15
Day
Bod
y w
eigh
t (g
)
Water Sucrose Fructose Glucose0
5
10
15
Bod
y w
eigh
t (g
)
Water Sucrose Fructose Glucose0
10
20
30
40
Bod
y w
eigh
t (g
)
0 3 6 9 12 15 18 210
5
10
15
Day
Bod
y w
eigh
t (g
)
Water
Sucrose
Fructose
Glucose
* p=0.001Sucrose vs AllRepeated Measures
✱ ✱
** p<0.01, *p<0.05
Water Sucrose0
500
1000
1500
2000
2500
Free
cho
line
(nm
ol/g
)
p=0.009
✱✱
Water Sucrose0
400
800
1200
Pho
spho
chol
ine
(nm
ol/g
)
✱
p=0.026
Water Sucrose0
500
1000
1500
2000
Betaine
(nmol/g)
✱✱
p=0.009
Free choline
Water Sucrose0
400
800
1200
(nmol/g)
p=0.036
✱✱
Phosphocholine Glycerophosphocholine BetaineFemale Male Female
Water Sucrose0
500
1000
1500
2000
2500
Free
cho
line
(nm
ol/g
)Water Sucrose
0
400
800
1200
Pho
spho
chol
ine
(nm
ol/g
)
Water Sucrose0
400
800
1200
(nmol/g)
Water Sucrose0
500
1000
1500
2000
Betaine
(nmol/g)
Male
** p<0.01, *p<0.05
p<0.05 sucrose vs all
0 3 6 9 12 15 18 210
5
10
15
Day
Bod
y w
eigh
t (g
)
Water
Sucrose
Fructose
Glucose
* p=0.001Sucrose vs AllRepeated Measures
✱ ✱
• Neonatal female and male mice (C57BL/6J) were randomly assigned to one of four treatment groups (n=7-10 mice/group/sex): sterile water, sucrose, fructose, or glucose.
• Pups were treated 10 times/day for the first six days of life with 0.2g/kg weight of respective treatments (1-4 μl/dose; 24% solutions) orally to mimic what is given to preterm babies.
• Mice were weaned at 3 weeks onto a control diet (D12450K Research Diets ®) and fed until age 16 weeks.
• Nose to anus length was measured on the day of euthanasia before cervical dislocation. Tibia length was treated in 2% KOH and measured using a digital caliper.
• Serum IGF-1 was measured using a commercial ELISA kit (ALPCO ®).
• Liver water-soluble choline metabolites were quantified by LC-MS/MS.