Regulação da proteólise e
ótimo acréscimo de proteína
nos recém-nascidos
extremamente prematuros
(Regulation of proteolysis and optimal protein
accretion in extremely premature newborns)
Scott C Denne
The Department of Pediatrics-Neonatology, Indiana University
School of Medicine , Indianapolis, IN.
Am J Clin Nutr. 2007;85:621S-624S.
Apresentação: Daniela Vilela
Coordenação: Albaneyde Formiga
Unidade de Neonatologia do Hospital Regional da Asa Sul
(HRAS)/SES/DF
INTRODUÇÃO
Resultados sobre crescimento em pré-termos
MMBP(<1000 g) continuam pobres;
 National Institutes of Health Neonatal Network documenta que 90-99% pré-termos MMBP
apresentam peso menor que o percentil 10 com 36
semanas de idade gestacional corrigida;
 Promover crescimento nos recém-nascidos 9RN)
pré-termos de muito muito baixo peso (PTMMBP)
requer mais compreensão em limitar a proteólise
e favorecer melhor incorporação protéica nesta
população.

PROTEÓLISE EM RECÉM-NASCIDOS PRÉTERMOS E TERMOS
A grande característica metabólica do pré-termo
extremo é a intensa proteólise (catabolismo
intenso); o dobro comparado em adultos
saudáveis.
 Administração de nutrientes em adultos
responde com redução da proteólise total,
enquanto que nos prematuros extremos a
supressão apresenta mais dificuldade; no adulto
a infusão de glicose aumenta a insulina
reduzindo a proteólise, resposta que é diferente
nos PTMMBP.

PROTEÓLISE EM RECÉM-NASCIDOS PRÉTERMOS E TERMOS
Hertz et al( Intravenous glucose suppresses
glucose production but not proteolysis in
extremely premature newborns,1993),
administrando TIG 6-9 observou altas taxas de
insulina e aminoácidos essências fenilalanina e
leucina sendo que proteólise não se
alterou(Figura-1).
 Avaliando a capacidade dos aminoácidos (aa)
administrados EV em suprimir a proteólise:
RN- termos – aa 1,2g/kg/dia redução 10%
aa 2,4g/kg/dia redução 20%
RN pré-termos – demonstraram resistência à
variação na proteólise (Figura-2).

Figura 1 Mean (±SE) leucine and phenylalanine rates of appearance (Ra)
(reflecting proteolysis) and insulin concentrations in extremely
preterm infants at 2 different glucose infusion rates: 6 (branco )
and 9 (preto ) mgkg–1min–1. *Significantly different from 6
mgkg–1min–1, P < 0.05. Data are from reference 6.
Figura 2 Mean (±SE) endogenous leucine rate of appearance (Ra; reflecting
proteolysis) in premature and term infants during the basal state ( )
and during graded infusion of amino acids: 1.2 (branco ) and 2.4 (preto
) gkg–1d–1. *Significantly different from basal, P < 0.05. **Significantly
different from 1.2 gkg–1d–1, P < 0.05. Data are from references 7 and
8.
PROTEÓLISE EM RECÉM-NASCIDOS PRÉTERMOS E TERMOS
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Administrando aminoácidos, lipídeos e glicose
associados equilibradamente em quantidades
suficientes para suporte de crescimento o grau de
proteólise total em pré-termos (PT) de 26sem e
PT de 32sem foi menos afetado.(Figura-3)
Quando se atinge a nutrição parenteral (NP)
plena 17% dos RN termo conseguem suprimir a
proteólise, mas nos prematuros praticamente não
se tem resposta.
Figura 3 Mean (±SE) percentage suppression of proteolysis from basal
values in response to full parenteral nutrition in 26-wk
gestation (gest) infants, 32-wk gestation infants, and full-term
infants. Data are from references 9 and 10.
SOLUÇÕES DE AMINOÁCIDOS E
PROTEÓLISE
Soluções de aminoácidos atuais não contem
glutamina, cistina e tirosina; uma potencial
explicação para limitação aos efeitos de proteólise
nos prematuros.
 Estudos com acréscimo destas proteínas estão
sendo feitos ; com glutamina mostrou significante
redução na proteólise em prematuros, entretanto
o efeito não foi visto nos pré-termos extremos.

ADMINISTRAÇÃO PRECOCE AMINOÁCIDOS
EV E INCORPORAÇÃO PROTÉICA
Apesar de limitações nas soluções atuais de
aminoácidos em inibir a proteólise nos PTMMBP,
está claro que o seu uso precoce resulta em
significante aumento de proteína sintética e
melhor balanço protéico.
 Rivera et al( Effect of intravenous amino
acids on protein metabolism of preterm
infants during the first three days of
life,1993), relata aumento de proteína sintética
em 40% nos pré-termos que receberam 1,5 g/kg/
dia aminoácido, tendo um balanço protéico
significante melhor(Figura-5).

Figura 4
Top panel: Leucine for protein synthesis and leucine balance in premature infants
receiving no amino acids (AA) or 1.5 g AAkg–1d–1. *Significantly different from no AA, P
< 0.05. Data are from reference 16. Bottom panel: Leucine for protein synthesis and
leucine balance in premature infants receiving amino acids at 1 or and 3 gkg–1d–1.
*Significantly different from AA 1, P < 0.005. Data are from reference 18. In both panels,
error bars indicate SEs.
ADMINISTRAÇÃO PRECOCE AMINOÁCIDOS
EV E INCORPORAÇÃO PROTÉICA

Thureem et al( Effect of low versus high
intravenous amino acids intake on very low
birth weight infants in the early neonatal
period,2003),examinado efeito 1 g versus 3g aa
/kg /dia houve aumento 35 % no grupo que
recebeu a maior taxa de aa( o efeito na proteólise
não alterou).
NUTRIÇÃO ENTERAL(NE) E PROTEÓLISE
NE é muito mais efetiva que NP na diminuição
efeito proteólise e aumento a incorporação
protéica.
 Van der Schoor et al( Lysine kinetics in
pretem infants: the importance of enteral
feeding,2004); proteólise foi 40% menor durante
a NE plena e o balanço protéico total significante
maior(Figura-5)
 Prematuros extremos não alcançam NE plena por
um período de semanas sendo proveitoso
combinar NP e NE, podendo assim diminuir
proteólise e aumentar incorporação protéica .

Figura 5
Mean (±SE) endogenous lysine rate of appearance (Ra; reflecting
proteolysis) and lysine balance during 60% parenteral and 40%
enteral nutrition (branco ) and full enteral nutrition (preto ).
*Significantly different from parenteral + enteral, P < 0.05. Data are
from reference 21.
PROTEÍNA VIA ENTERAL E AUMENTO
INCORPORAÇÃO PROTÉICA
Fazer a transição equilibradamente NP para NE
nos pré -termos extremos, a fim de aumentar a
incorporação protéica, continua sendo um
significante desafio clinico.
 Embleton et al (Postnatal malnutricion and
growth retardation: an inevitable
consequence of current recommendation in
pretem infants?,2001); relata a dificuldade de
incorporação protéica nos pré-termos < 30 sem
recebendo NE plena com formulas padrão para
estes, sugerindo ter beneficio aumentar conteúdo
protéico nas formulas interais.

PROTEÍNA VIA ENTERAL E AUMENTO
INCORPORAÇÃO PROTÉICA
Zello et al( Minimum protein intake for the
preterm neonate determined by protein and
amino acid kinetics,2003); há uma correlação
linear entre o balanço protéico ofertando maior
proteína -1 -1,5 g/kg/dia.
 Cooke et al ( High protein pre-term infant
formula: effect on nutrient balance,
metabolic status and growth,2006); estuda
um balanço protéico ainda maior administrando
proteínas 3,4 -6,2 g /kg /dia.
 Estudos com um grupo controle maior, usando
formula com alto conteúdo protéico é necessário.

EM RESUMO;
Administrar aminoácidos EV precoce 3 g /kg/dia
pode aumentar a incorporação protéica e o
crescimento PTMMBP ;
 Pré-termos aparentemente tem resistência aos
efeitos anti- proteolíticos da NP; estudos
examinando uma melhor composição dos
aminoácidos na proteólise são promissores ;
 Promover uma sistemática investigação sobre os
efeitos nutrição enteral(NE) plena e a
combinação NP e NE na proteólise aumentando
incorporação protéica ;
 Priorizar estudos a fim de melhorar formulas
atuais para PT, suprindo as necessidades
protéicas dos PTMMBP.



ABSTRACT
Growth outcomes for extremely premature infants remain poor,
and improving growth in this population will require a better
understanding of how to limit proteolysis and promote protein
accretion. Extremely premature infants exhibit high rates of
proteolysis that are unrestrained by physiologic increases in
insulin, intravenous amino acids, and full parenteral nutrition.
Imbalances in current amino acid solutions may be in part
responsible for the inability of parenteral nutrition to reduce
proteolysis in preterm infants. However, amino acids in
parenteral nutrition are effective for increasing protein synthesis
in extremely preterm infants, which leads to improved protein
balance. Current evidence suggests that early administration of 3
g amino acidskg–1d–1 to extremely premature infants is safe and
effective. Enteral nutrition may be more effective than parenteral
nutrition in limiting proteolysis and producing protein accretion
in preterm infants, but the protein content of current preterm
formulas may be inadequate for supporting optimal growth in
this population. Important areas of future research include
determining whether altered intravenous amino acid solutions
can better effect reductions in proteolysis, investigating the effect
of enteral nutrition on proteolysis and protein accretion, and
conducting a large randomized controlled trial of formula with a
higher protein content.
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