FISIOLOGIA BACTERIANA y mecanismos de acción (1).pptx
Importancia concentración proteína en la alimentación del lactante
1. XXII Congreso Nacional de Pediatría
Managua 15-16 de Agosto 2014
Importancia de la concentración de la
proteína en la alimentación del lactante
sobre el crecimiento
Dr. Marco Rivera Meza
Médico – Pediatra
HBCR- SUMEDICO
4. Ingesta de Proteínas
Beneficios de la mayor ingesta de proteínas
Mayor crecimiento y volumen del tejido
magro
Aumento en la construcción de huesos
Aumento construcción y componentes
sanguíneos
Mejoría en la síntesis de las hormonas.
La deficiencia de proteínas en la infancia
Puede causar fallas en el crecimiento
Casos extremos: puede llevar a un edema
Menor resistencia a las infecciones.
5. Sin embargo….
El exceso de proteína aumenta la
urea en sangre, iones de hidrógeno, y
aminoácidos (es decir, fenilalanina,
tirosina), lo que resulta en acidosis
metabólica
7. Hipotesis y Guías de FDA
►La ganancia de peso de los infantes con una formula experimental
(EF) deberá ser:
◦Similar a los bebés alimentados al pecho materno (BF)
◦De 3 gramos por día en los infantes alimentados con una formula
estandar (SF)
Guía de la FDA para una nueva formula infantil
►FDA y otras autoridades internacionales reconocen el crecimiento y
el aumento de peso como indicadores importantes de la inocuidad e
idoneidad de los preparados para lactantes
►La Orientación establece que cuando se realiza un cambio en la
composición de macronutrientes de una fórmula, la ganancia de
peso de los bebés alimentados con la nueva fórmula debe ser
mayor y no menor de 3 gramos por día y sin diferencia de los bebés
alimentados con la fórmula estándar o control
Hipótesis
8. Si el aumento de peso difiere en más
de 3 gramos / día, la fórmula
experimental no se debe considerar
segura
Es por eso que….
9. α-Lactoalbúmina
En la leche humana es la principal
proteína del lactosuero, aumentando
sus niveles desde un 21% hasta un
34% del día 1 al 14 de la lactación, y
alcanzando en la Leche madura
(después del día 30) una
concentración de 2,44 g/L
Funciones
Efectos derivados aporte de aa esenciales: Triptófano
Efectos sobre absorción de minerales
Actividad anti - carcinogénica
Actividad prebiótica
Actividad sobre sistema inmune – antimicrobiana
Otros: anti - hipertensiva, opioide, anti – oxidante
10. Diseño de estudio clinico
Formula Fed
n = 224 Infants
Breast Fed
n = 112 Infants
Experimental Formula (EF)
12.8 g/L protein
ENROLL
n = 112
Breast milk (BM)
11 – 12 g/L protein
ENROLL
n = 112
Standard Formula (SF)
14.1 g/L protein
ENROLL
n = 112
Sujetos: Infantes a término sanos, 5 - 14 dias de vida
Duracion del estudio: 120 dias
Objetivo Primario: Comparar crecimiento de infantes randomizados EF versus SF y BM
Objetivos Secundario: Evaluar proteina y concentración plasmatica de aa esenciales.
Evaluar tolerancia gastrointestinal
randomized
reference
group
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
11. Formula Fed
n = 224 Infants
Breast Fed
n = 112 Infants
Experimental Formula (EF)
12.8 g/L protein
ENROLLED
n = 112
Breast milk (BM)
11 – 12 g/L protein
ENROLLED
n = 112
Standard Formula (SF)
14.1 g/L protein
ENROLLED
n = 112
randomized
reference
group
Study Enrollment and Completion
Completed
n = 108
Discontinued
n = 4
Completed
n = 103
Discontinued
n = 9
Completed
n = 110
Discontinued
n = 2
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula with lower protein on growth.
EJCN (2011) 65, 167–174.
Inscripción y realización
321 de 336 (96%) infantes se inscribieron y completaron el estudio
13. Mean Weight Gain Velocity:
Standard Formula Compared to Breast Fed Group
Weight Gain Velocity: Day 120
20
22
24
26
28
30
32
Treatment groups
Meanweightgainvelocity(g/d)
p = 0.0413
SF EF BF
■ Standard Formula group
■ Breast fed group
• Ganancia de peso en grupo SF fue significativamente mayor que en el
grupo BF
Velocidad media en la ganancia de peso:
Fórmula Standart comparada con leche materna
14. Mean Weight Gain Velocity:
Experimental Formula Compared to Breast Fed Group
20
22
24
26
28
30
32
Treatment groups
Meanweightgainvelocity(g/d)
Weight Gain Velocity: Day 120
SF EF BF
NS
■ Experimental Formula group
■ Breastfed group
• No se encontraron diferencias significativas entre el EF y BF
Velocidad media en la ganancia de peso:
Fórmula experimental comparada con leche materna
15. Mean Weight Gain Velocity:
All Groups
Weight Gain Velocity: Day 120
20
22
24
26
28
30
32
Treatment groups
Meanweightgainvelocity(g/d)
p = 0.0413
NS
SF EF BF
NS ■ Standard Formula group
■ Experimental Formula group
■ Breastfed group
• Ganancia de peso en el grupo EF no diferencia significativa con el grupo BF
• Crecimiento con EF según guía FDA es seguro en nueva formula infantil
Velocidad media de ganancia de peso:
Todos los grupos
16. Weight for Age Z-scores:
All Subjects
Weight for Age Z-scores
All Subjects
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
baseline study day 30 study day 60 study day 90 study day 120
MeanWeightforAgeZ-score
SF EF BF
* EF significantly different than BF
* SF significantly different than BF
** *
Usando grafico crecimiento OMS, peso para edad score Z No se observaron diferencias
significativas en los grupos EF y BF al final del estudio
Peso para edad scores - Z
17. Weight for Length Z-scores:
All Subjects
Weight for Length Z-scores
All Subjects
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
baseline study day 30 study day 60 study day 90 study day 120
MeanWeightforLengthZ-score
*
*
*
*
* EF significantly different than BF
* SF significantly different than BF
SF EF BF
Peso para Talla score - Z
Usando grafico crecimiento OMS, peso para talla score Z No se observaron diferencias
significativas en los grupos EF y BF al final del estudio
18. Infant growth on WHO growth charts
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
Crecimiento de infantes en curvas OMS
19. X
X
X
X
X
X = BF group
Weight-for-Length of Infants Fed Experimental Formula
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
Crecimiento de infantes en curvas OMS
20. X
X
X
X X
X = BF group
= EF group
Peso – talla para infantes alimentados EF es similar al grupo BF
Weight-for-Length of Infants Fed Experimental Formula
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
Crecimiento de infantes en curvas OMS
21. Weight-for-Length of Infants Fed Experimental Formula
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
Crecimiento de infantes en curvas OMS
22. X = BF group
X
X
X
X
X
Weight-for-Length of Infants Fed Experimental FormulaCrecimiento de infantes en curvas OMS
23. X = BF group
= EF group
X
X
X
X
X
Weight-for-Length of Infants Fed Experimental Formula
Peso para Talla en Infantes con EF fue similar al grupo BF
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
Crecimiento de infantes en curvas OMS
24. Conclusion
►Infantes alimentados con EF no difirieron en el
crecimiento de los alimentados con BF en los
parametros:
◦Ganancia en la velocidad media de peso
◦Peso para edad/Talla en el score-Z
◦Peso para la Talla
La tasa de crecimiento en infantes alimentados
con EF baja en proteínas enriquecida con alfa-
lactoalbúmina fue comparable con el crecimiento
de infantes que fueron alimentados con pecho
materno – en este estudio clínico controlado -
Conclusiones relacionadas al crecimiento
26. Protein Status
Total Protein
48
53
58
63
68
73
78
baseline day 60 day 120
MeanTotalProteinconcentration(g/L)
* EF significantly different than BF
* SF significantly different than BF
SF EF BF
El estado de los Marcadores proteicos fueron normales para todos los grupos
Estado de las Proteinas
Albumin
30
35
40
45
50
baseline day 60 day 120
MeanAlbuminconcentration(g/L)
**
27. Glucose
Day 60
60
70
80
90
100
110
Glucose
meanGlucoseconcentration(mg/dl)
NS NS
NS
SF EF BF
Insulin
Day 60
0
3
6
9
12
15
18
INSULIN
meanInsulinconcentration(mcU/mL)
NS NS
NS
SF EF BF
Glucose and Insulin Concentrations
Insulin
Concentraciones Medias de glucosa e insulina fueron similares en todos los
grupos
Data on File. Wyeth Nutritionals Clinical Study Report 9052A1-3000
Concentraciones Post-prandiales glucosa/insulina
28. 0
50
100
150
200
250
300
Standard Formula Experimental Formula Human Milk
Mean ± 95% Confidence Interval (of the Standard Deviation)
*Statistically significant difference between EF and BF, p-value adjusted for multiplicity (p < 0.0015)
µmol/L
Cystine
Leucine
Histidine
*Isoleucine
*Methionine
*Phenylalanine
*Threonine
Tryptophan
*Tyrosine
*Lysine
Valine
Breast Fed
Concentraciones plasmáticas post – pandrial de Amino-ácidos
Trabulsi et al, Effect of an a-lactalbumin-enriched infant formula
with lower protein on growth. EJCN (2011) 65, 167–174.
29. Baja concentración de proteínas en la formula era apropiado para RN
Crecimiento sostenido
Marcadores proteicos dentro de los límites normales
Concentraciones de aa esenciales en Plasma similares o > que
lactancia materna
Crecimiento con formula baja en proteina fue similar a lactancia materna
en:
Tasa de ganancia de peso
Peso por Edad en Z-score
Peso para talla en Z-score
Tolerancia Gastrointestinal de la formula baja en proteina fue favorable
Bajo puntaje GI índice de síntomas (resultado informado por el padres)
Resumen
30. Resultados del estudio versus otros estudios
La evidencia de una relación positiva entre la
concentración de proteínas de la alimentación y el
aumento de peso se apoya en estudios aleatorizados
y observacionales
Varios ensayos prospectivos aleatorizados encuentran que los
niños que recibieron una fórmula más alta de proteína en
comparación con los que recibieron una fórmula de proteína
baja tienen:
• Mayor ganancia de peso (Raiha et al, 1986;.. Axelsson et al,
1989)
• Mayor peso y talla (Koletzko et al., 2009)
31. Resultados del estudio versus otros estudios
• Algunos ensayos prospectivos aleatorizados no han
encontrado diferencias en el crecimiento de los niños
alimentados con Fórmula bajas en proteínas versus altas
– Janas et al., 1987
– Picone et al., 1989
– Turck et al., 2006
• Estos estudios tienden a tener un tamaño de muestra
más pequeños, además de pequeñas diferencias en la
concentración de proteína entre las fórmulas
32. Resultados del estudio versus otros estudios
• Estudios de cohortes observacionales, han demostrado
una asociación entre el índice de masa corporal y
aumento de sobrepeso a la edad de 5-8 años :
• Mayor ingesta proteica (Gunnarsdottir and Thorsdottir, 2003)
• Mayor porcentaje de energía alimentaria en forma de
proteínas (Rolland-Cachera et al., 1995; Scaglioni et al., 2000)
• También se ha demostrado una asociación entre el
aumento de peso y la obesidad en la infancia más tarde
(Stettler et al., 2002; Ong et al., 2009)
33. Resultados del estudio versus otros estudios
En resumen, la concentración de proteínas en la
alimentación infantil desempeña un papel fundamental en el
aumento de peso durante la infancia, lo que a su vez
afectaría más su peso en el transcurso de la vida. Esto
subraya la importancia de la resultados de la ganancia de
peso observada en el grupo EF en el presente ensayo clínico
34. Otras observaciones
• La concentración de proteína de la primera fórmula (Inicio) de
aproximadamente 12 - 13 g / L de proteína está muy cerca de la
concentración de proteína total medio de la leche materna
Totalprotein,g/L
35. Otras observaciones: fórmulas de seguimiento (6-12 meses)
• Muchas fórmulas de seguimiento, en particular de los países
en donde las regulaciones de fórmulas infantiles están en línea
con el Codex Alimentarius, tienen concentraciones de proteínas
totales que son mucho más altos que la leche materna
Totalprotein,g/L
Follow – on
~20 g/L
36. Baja concentración de proteinas en primer año y
fórmulas de seguimiento
Formula Fed
n = 1138 Infants
Breast Fed
n = 619 Infants
randomized
reference
group
Higher Protein
infant formula
20.5 g pro/L
(0-6 months)
Breast milk (BM)
11 – 12 g/L protein
ENROLL
n = 112
Lower Protein
infant formula
12.5 g pro/L
(0-6 months)
Higher Protein
follow on formula
32.0 g pro/L
(6-12 months)
Lower Protein
follow on formula
16.0 g pro/L
(6-12 months)
(AJCN 2009)
39. Conclusion
Teniendo en cuenta el efecto que la dieta hace sobre el
crecimiento en la infancia es importante tener en
cuenta la ingesta de proteínas a lo largo de la vida
temprana, a partir del nacimiento
FF infants were randomly allocated to one of the study formulas.
The study was designed to enroll at total of 336 infants, 224 infant were FF and randomized to receive either Standard or Experimental formula. A total of 112 breast fed infants were enrolled as a reference group
A total of 321 infants (96%) completed the study.
SF Discontinued group:
3 AE: Vomiting (n=1), Constipation (n=1), Diarrhea (n=1)
1 Parent Request: advise from relatives to not participate in study (n=1)
EF Discontinued group:
3 AE: Gastro esophageal reflux disease (n=3)
6 Parent Request: refused blood extraction (n=3), parents moved (n=2), family problem/separation (n=1)
HM Discontinued group:
Lost to follow up (n=1)
Death (n=1): subject had a congenital malformation that was not apparent at enrollment; subject diagnosed with aqueduct stenosis
Total protein concentration of our term infant formula to 13 g/L
Key point
Moving to the results, we will review the data related to Growth first
Growth was evaluated in terms of weight gain velocity, Z-scores, and change in Z-score.
In addition to growth, the primary objective, this study also evaluated
Protein status and blood urea nitrogen concentrations
Post-prandial amino acid, glucose, and insulin concentrations among groups
Gastrointestinal tolerance
Before we discuss the results shown in this graph, let’s go over a few points to help you understand what you see here.
Weight gain velocity is a measure of rate, in other words is the amount of weight gain within a specified time period (usually expressed in g/d). Actual weight gain refers to the absolute amount of weight gained; it would be expressed in grams.
Weight gain velocity was utilized because the FDA and other international authorities recognize it as an important assessment in the suitability of infant formula.
This graph and 2 others to follow represent the primary efficacy endpoint, weight gain velocity over the course of the entire study, from baseline to day 120; a difference in weight gain velocity was observed between groups after 4 months of feeding (day 120).
The results demonstrate that the weight gain velocity of infants was significantly higher in the standard formula group versus the HM group.
Key Points
Weight gain velocity of infants was significantly higher in the standard formula group
versus the HM group
Rate of gain in length and head circumference of infants fed Experimental formula was similar to and at some time points slightly greater than that of the HM group, these data demonstrate that we were able to lower the total protein content of the formula without compromising growth.
Statistical Notes: Mean weight gain velocity: SF: 28.1 g/d; BF: 26.6 g/d
The weight gain velocity of the EF group was not significantly different from the HM group
Statistical Notes: Mean weight gain velocity: EF: 27.8 g/d; BF: 26.6 g/d.
Key Points
Weight gain velocity of infants fed EF was closer to HM and did not differ significantly from HM
These data support the hypothesis that the protein concentration of the formula plays a role in
weight gain velocity
The mean weight gain in all evaluable subjects in the SF and EF groups was comparable. The weight gain velocity of the EF group was intermediate between the SF and the breast fed group. The weight gain velocity of the EF group was not significantly different from the HM group
Key Points
Weight gain hypothesis was confirmed, weight gain velocity of the EF group was
intermediate between the SF and HM group
2. Weight gain of the EF group did not differ significantly from the breast fed group
3. These data suggest that even a modest reduction in the protein concentration of the
formula can have a effect of weight gain velocity
Statistical Notes: Mean weight gain velocity: SF: 28.1 g/d; EF: 27.8 g/d; HM: 26.6 g/d.
Like we did before, let’s take a minute to go over a few points to help you understand what you see here
1) A z-score is the deviation of the value for an individual from the mean value of the reference
population divided by the standard deviation for the reference population. A z-score of 0
means that the study population has the same growth parameters as the reference population.
2) The reference population for these Z-score data are the World Health Organization (WHO)
growth charts.
3) We would expect nearly all infants in a population to fall within +2.0 and -2.0 Z-scores.
Background on WHO growth charts
These growth standards were developed using data collected in the WHO Multicentre Growth Study. These standards represent the growth of healthy infants and children from six countries: Brazil, Ghana, India, Norway, Oman, and the United States. Subject were fed according to WHO feeding recommendations (which include breast feeding for 12 months with complementary foods introduced only after 6 months).
The comparison of the SF vs HM groups at baseline showed a significant difference between groups in weight-for-age.
EF had a weight for age z-score similar to HM fed infants at the end of the study
This is the first of several graphs that will be presented
The study visits are on the x-axis
Mean Z-score along the y-axis
SF blue, EF red, HM green
Red * EF signif from HM, blue * SF signif diff HM
EF infants had a WLZ similar to HM fed infants at the conclusion of the study SHOWS WT IN PROPORTION TO LENGTH- WANT APPROPRIATE WT FOR LENGTH
2) The formula fed infants started the study with a weight for length that was greater than the HM group
3) and after a 4 months of receiving the study formula or breast feeding, the weight for length was similar among groups.
We were also interest in the change in WLZ from baseline to the completion of the study
Key point
Moving to the results, we will review the data related to Growth first
Growth was evaluated in terms of weight gain velocity, Z-scores, and change in Z-score.
In addition to growth, the primary objective, this study also evaluated
Protein status and blood urea nitrogen concentrations
Post-prandial amino acid, glucose, and insulin concentrations among groups
Gastrointestinal tolerance
The y-axis for all analytes is scaled according to the lower and upper range of normal.
For example, the lower end of the range for albumin is 30 g/L and the upper limit is 50 g/L
The EF group had the highest albumin concentration at the end of the study,
The BUN concentration at day 120 were consistent with the protein concentration of the feedings,
The SF group had the highest BUN followed by the EF and HM group
In general though, means of all groups were within the normal range
Key Point
Mean blood urea nitrogen concentration was within normal limits for all groups at all time points.
Mean BUN concentrations at day 60 and day 120 were consistent with total protein concentration of the feeding, BUN concentrations were lowest in the HM group and highest in the SF group.
Key Points:
Mean glucose and insulin concentrations did not differ between groups
.
Key Points:
Mean glucose concentration did not differ between groups
Mean glucose concentrations were within normal range for all groups.
Mean insulin concentration did not differ between groups.
A Normal reference range for insulin concentration in infants has not been established.
Key points
Mean plasma essential amino acids concentrations of the formula fed infants were similar to or greater than those of HM group normal range
2. No significant differences in mean amino acid concentration between SF and EF group
3. These data indicate that while the total protein concentration of the formula was decreased, infants in the EF group were supplied with sufficient quantities of essential amino acids.