Clinical Feeding
Content
[clinical p ra c ti c e g ui de li n es
*
guides
de
pratique clinique]
AND D FEEDING N U T R I E N T N E E D S AN OF PREMATURE I N F A N T S Nutrition Committee, Ca n a d i a n Paediatric Society
Objective: ture
To r e c o m m e n d
infants.
Options: Unfortified f a n t ' s own m o t h e r ,
appropriate intake of nutrients,
food
sources
and
feeding practices for
prema-
own m o t h e r , f o r t i f i e d m i l k f r o m t h e p r e m a t u r e i n m i l k f r o m t h e p r e m a t u r e i n f a n t ' s own formula d e s i g n e d f o r preterm i n f a n t s a n d p a r e n t e r a l nutrition
Outcomes: From birth
to 7
days,
th e minimum a c h i e v a b l e
provision i n premature i n f a n t s ; goal
is the
of sufficient nutrients to
from 7 d a y s to d i s c h a r g e d e f i c i e n c i e s a n d c a t a b o l i s m of n u tr i en t substrate f r o m t h e n e o n a t a l i n t e n s i v e c ar e u n i t , g r o w t h a n d n u t r i e n t r e t e n t i o n a t a r a t e s i m i l a r t o t h a t w h i c h w o u l d h a v e b e e n a c h i e v e d h a d the i n f a n t r e m a i n e d i n u t e r o ; a n d f o r 1 y e a r f o l l o w i n g d i s c h a r g e , nutrie n t i n t a k e to achieve c a t c h- u p g r o wt h . E v i d e n c e : F e w r a n d o m i z e d c l i n i c a l t r i a l s of f e e d i n g i n f a n t s s p e c i f i c n u t r i e n t s o r o f f e e d i n g c h o i c e s have b e e n c o n d u c t e d . O n t h e b a s i s o f a M E D L I N E s e a r c h of t h e l i t e r a t u r e , c o m m i t t e e members p r e p a r e d re v i e w s o f t h e a v a i l a b l e i n f o r m a t i o n on e a c h n u t r i e n t a n d f e e d i n g c h o i c e . T h e r e v i e w s w e r e c r i t i c a l l y a p -
prevent
praised by
the committee. R e c o m m e n d a t i o n s
p o s s i b l e , the e v i d e n c e u n a v a i l a b l e , cohort s t u d i e s
Values: W h e n e v e r
trials
were
lished Benefits,
was
were
based
on
t h e consensus o f t h e c o m m i t t e e .
w e i g h e d i n f a v o u r o f ran d o m i z ed c o n t r o l l e d t r i a l s . I f
were c o n s i d e r e d .
u n a v a i l a b l e , pub-
I f t r i a l s o f e it he r k i n d w e r e
d a t a were r e v i e w e d a n d r e c om me n d a t i on s were b a s e d o n consensus o p i n i o n . h a r m s a n d c o s t s : Th e a d v a n t a g e s o f f e e d i n g p r e m a t u r e i n f a n t s u n f o r t i f i e d m i l k f r o m t h e i r
mothers
ar e
psychologic
benefits
for
such
own own
possibly
t h e mother a s w e l l a s a n t i - i n f e c t i v e b e n e f i t s a nd
im -
own m o t h e r p r o v e d i n t e l l e c t u a l d e v e l o p m e n t f o r t h e i n f a n t . H o w e v e r , u n f o r t i f i e d m i l k f r o m t h e i n f a n t ' s own i s i n a d e q u a t e a s a s o l e s o u r c e o f n u t r i e n t s . Th e us e o f f o r t i f i e d m i l k fro m t h e m o t h e r r e s u l t s i n f a s t e r
growth
infants plicate
as ar e
h a v i n g t h e o t h e r b e n e f i t s of m o t h e r ' s m i l k . i n given a d e q u a t e v o l u m e s , t h e y p r o v i d e an i n t a k e
well
as
When f o r m u l a s
designed
for
premature
o f n u t r i e n ttss t h a t a l l o w s t h e i n f a n t t o d u -
intrauterine growt h w i t h o u t u n d u e me t abolic s t r e s s .
own m o t h e r p r e f e r r e d f o o d f o r p r e m a t u r e i n f a n t s i s f o r t i f i e d m i l k f r om t h e i n f a n t ' s own or , a l t e r n a t i v e l y , f o r m u l a d e s i g n e d f o r p r e m a t u r e i n f a n t s . T h i s r e c o m m e n d a t i o n a p p l i e s t o i n f aann t s w i t h b i r t h w e i g h t s o f a m i n i m u m o f 5 0 0 g t o a m a x i m u m o f 1 8 0 0 t o 2 0 0 0 g , o r wi t h a g e s t a t i o n a l a g e a t b i r t h
R e c o m m e n d a t i o n s : Th e
of
a
minimum o f 2 4 w e e k s t o
Validation: These
guidelines
m a x i m u m of 3 4 t o 3 8 weeks ( u n t i l t h e i n f a n t i s a b l e t o
a
ar e
in line
with,
bu t n ot identical
to,
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guidelines by
nurse
effectively).
t he C o m m i t t e e on
N u t r i t i o n o f t h e A m e r i c a n A c a d e m y o f P e d i a t r i c s a nd t h e C o m m i t t e e o n N u t r i t i o n o f t h e P r e t e r m f a n t o f t h e E u r o p e a n S o c i e t y of P a e d i a t r i c G a s t r o e n t e r o l o g y and N u t r i t i o n .
Sponsor:
Objectif:
Th e
preparation
Re c o m m an d e r
of t h e s e
un
guidelines
apport
m e n t a t i o n p ou r l e s n o u v e a u - n e s
was
s p o n s o r e d and funded b y t h e Canadian
approprie de nutriments, prematures.
d e s so urces
d'aliments
In -
Paediatric Society.
et d e s pratiques
d'ali-
Nuon C o m m i t t e e o f t h e C a n a d i a n P a e d i a t r i c S o c i e t y : D r s . T i l a k R . M a i h o t r a ( d i r e c t o r r e s p o n s i b l e ) , H o l y F a m i l y a nd V i c t o r i a U n i o n H o s p i t a l s , P r i n c e A l b e r t , S a s k . ; S t a n l e y H . Z l o t k i n ( c h a i r ) , D e p a r t m e n t o f P a e d i a t r i c s , H o s p i t a l f o r S i c k C h i l d r e n , T o r o ntn t o , O n tt.. ; M a r g a r e t P . B o l a n d , C h i l d r e n ' s H o s p i t a l o f E ast ern O n t a r i o , O t t a w a , O n t . ; R o b e r t M. I ssen m an , D e p a r t m e n t of P a e d i a t r i c s , M c M a s t e r U n i v e r s i t y , H a m i l t o n , O n t ; E l i z a b e t h R o u s s e a u - H a r s a n y , H o p i t a l S a i n t e - J u s t i n e , M o n t r e a l , Q u e . ; J o h n E . E . Va n A e r d e , D e p a r t m e n t of P a e d i a t r i c s , U n i v e r s i t y of A l b e r t a , E d m o n t o n ,
Alta.
il d r en en , T o r ro onto o, , O n t . ; Stephanie A. S c i e n t i f i c R e v i e w S u b c o m m i t t e e r e s p o n s i b l e f or t i e p r e p a r a t o n o f t h e s e g u i d e l i n e s : D r s . S t a n l e y H . Z l o t k i n ( c h a i r and p r i n c i p a l c o a u t h o r ) , H o s p i t a l fo r S i c k C h il D u n n , Woman s C o l l e g e H o sp i t a l, Toronto f o r O n t ; M i c h a e l Sick J o a n M s . T o r o n t o , C h i l d r e n , D r s . R P D t , M c M a s t e r B r e n n a n , H o s p i t a l o f O n t ; University, Hamilton, Atkinson, D e p a r t m e n t Paediatrics, M. I n n i s , Department of P ae di at r i c s , U n i v e r s i t y of B r itis h C o l u m b i a , S h e i l a fo r S i c k O n t ; T o r o n t o , C h i l d r e n , S t . M i c h a e l ' s T i b o r H e i m , R h o n a T o r o n t o , O n t ; H o s p i t a l Hospital, Hanning, Ont; ck V a n c o u v e r , B C ; G i l l i a n L o c k i t c h , B r i t i s h C o l u m b i a ' s C h i l d r e n ' s H o s p i t a l , V a n c o u v e r , B C ; M s . S u s a n M e r k o , R P D t , W o m e n ' s C o l l e g e H o s p i t a l , T o r o n t o , O n t . ; D r s . P a u l B . P e nc h a r z , H o s p i t a l f o r S i ck of Un i ve r s i t y of fo r T o r o n t o , O n t ; D e p a r t m e n t C h i l d r e n , Re g S i c k S i c k R a d d e , l n g e b o r g O n t ; M a x f o r O n t . ; C h i ld l d r e n , T o r o n t o , P a e d i a t r i c s , Hospital Children, Toronto, Perlman, Hospital Sauve, C a l g a r y , A l t a . ; a n d J o h n E . E . V a n A e r d e , D e p a r t m e n t of P a e d i a t r i c s , U n i v e r s i t y o f A l b e r t a , E d m o n t o n .
R e p r i n t r e q u e s t s to: N u t r i t i o n
*+-
C o m m i t t e e , C a n a d i a n P a e d i a t n c S o c i e t y , 40 1 S m y t h R d . , O t t a w a ON
F o r pp rr ee ss cc rr ii bb ii nn gg i n f o r m a t i o n ss ee ee pp aa gg ee 11 9 22 44
KlH8LH
C AN M E D ASSOC J
1995; 152
11 )
JUNE 1, 1995; 152 (1 1)
o
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Options: L a i t n on f o r t i f i e d e l a mere d u n o u v e a u - n e p r e m a t u r e , l a i t m a t e r n e l f o r t i f i e d e l a mere du n o u ve au -ne premature, lait mat e r nise p o u r n o u v e a u - n e s p r e mat ur e s et alimentation parenterale. R e s u l t a t s : De l a n a i s s a n c e a 7 jours, l o b j e c t i f m i n i m u m a t t e i n d r e est un a p p o r t suffisant en n u t r i m e n t s pour p r e v e n i r d e s c a r e n c e s e t l e c a t a b o l i s m e d u s u b s t r a t d e n u t r i m e n t s c h e z l e s n o u v e a u - n e s p r e m a t u r e s ; d e 7 j o u r s a l a l i b 6 r a t i o n d e l u n i t e d e s s o i n s i n ttee n s i f s n e o n a t a u x , c r o i s s a n c e e t r e t e n t i o n d e s n u t r i m e n t s a un t a u x c o m p a r a b l e a u t a u x q u i a u r a i t et a t t e i n t si l e n o u r r i s s o n e t a i t d e m e u r e d a n s l e s e i n d e s a m e r e ; p e n d a n t I a n a p r e s l a l i b e r a t i o n , a p p o r t d e n u t r i m e n t s pour r e a l i s e r u n r a t t r a p a g e d e c r o i s -
sance.
r a n d o m i s e s s u r l e s n u t r i m e n t s s p e c i fi q u e s a b s o r b e s p a r l e s nouveau-nes ou s u r l e s c h o i x d ' a l i m e n t a t i o n s o n t p eu nombreux. S ' a p p u y a n t s u r une r e c e n s i o n d e s e c r i t s d a n s M E D L I N E , les membres du c o m i t e o n t p r e p ar e de s examens des r e n s e i g n e m e n t s disponibles sur c h a q u e n u t r i m e n t
Preuve: L e s essais cliniqu es
e t c h a q u e c h o i x d a l i m e n t a t i o n . L e comite a p r o c e d e a u n e e v a l u a t i o n c r i t i q u e d e s r e v u e s . S e s recomm a n d a t i o n s s o n t f on d e e s sur un co nsensus. Valeurs: L o r s q u e c e f u t p o s s i b l e , on a p o n d e r e l e s p r e u v e s en f a v e u r d e s e s s a i s c o n t r 6 l e s r a n d o m i s e s . L o r s q u e d e t e l s e ssais n ' 6 t a i e n t p a s d i s p o n i b l e s , on a e n v i s a g e d e s e t u d e s d e c o h o r t e s . S il n'existait p a s d'essais d e l u n ou l a u t r e d e s deux t y p e s , on a examine l e s d o n n e e s p u b l i e e s e t f o n d e l e s recommandations sur le consensus. A v a n t a g e s , p r e j u d i c e s e t c o u i t s : L e s a v a n t a g e s q u e p r e s e n t e pour l e s e n f a n t s p r e m a t u r e s u n e a l i m e n t a t i o n f o n d e e s u r l e l a i t m a t e r n e l n on f o r t i f i e s o n t d 'o rd re p s y c h o l o g i q u e p o u r l a mere e t p r e s e n t e n t a u s s i un moyen de lutte c o n t r e l'infection et, peut-etre, de d e v e l o p p e m e n t intellectuel a m e l i o r e p o u r le n o u v e a u - n e . L e l a i t n o n f o r t i f i e d e l a m e r e d u n o u v e a u - n e n e s u f f i t t o u t e f o i s p a s comme s e u l e s o u r c e d e n u triments. L e lait m a t e r n e l fortifie accelere la croissance et offre aussi les autres a v a n t a g e s du lait m a t e r nel. Lorsqu'on donne a u x n o u v e a u - n e s s u f f i s a m m e n t d e lait m a t e r n i s e p o u r p r e mat ur e s, le lait fournit un a p p o r t d e n u t r i m e n t s q u i r e p r o d u i t chez l e s nouveau-n6s l a c r o i s s a n c e i n t r a - u t e r i n e s a n s c a u s e r d'effort metabolique inutile. Recommandations: L ' alim entatio n privilegi6e c h e z l e s n o u v e a u - n e s p r e m a t u r e s est le lait f o r t i f i e de la mere du nouveau-ne c omme s o l u t i o n d e le lait pour m a t e r n i s e r e c h a n g e , o u , m a n d a t i o n v a u t p o u r l e s n o u v e a u - n e s d o n t l e p o i d s l a n a i s s a n c e v a r i e d ' a u m op ir ne sm a 5t 0u r0e gs . j uCseq tu t ae r1 e 8c 0o m0i 2 0 0 0 g , o u d o n t 1 S a g e d e l a g r o s s e s s e a l a n a i s s a n c e v a r i e d ' a u m o i n s 2 4 s e m a i n e s a a u p l u s 34 a 3 8 s e maines ( j u s q u a c e que l e nouveau-ne p u i s s e t e t e r e f f i c a c e m e n t ) . V a l i d a t i o n : C e s l i g n e s d ir ec tr i ce s s o n t c o n f o r m e s mais n on i d e n t i q u e s au x l i g n e s d i r e c t r i c e s e t a b l i e s r e c e m m e n t p a r l e Committee on N u t r i t i o n d e l ' A m e r i c a n A c a d e m y o f P e d i a t r i c s e t p a r l e Committee on N u t r i t i o n o f t h e P r e t e r m In f a n t d e l a E u r o p e a n S o c i e t y o f P a e d i a t r i c G a s t r o e n t e r o l o g y and N u t r i t i o n . Commanditaire: L a p r e p a r a t i o n de c e s lignes directrices a et commanditee et f i n a n c e e p a r la S o c i e t e
canadienne de pediatrie.
S i nc e t he Canadian P a e d i a t r i c S o c i e t y (CPS) p u b l i s h e d recommendations c o n c e r n i n g t h e f e e d i n g o f p r e m a t u r e infants in 1 9 8 1 , ' t h e r e h a v e been enormous a d v a n c e s i n t h e t y p e an d q u a l i t y o f c l i n i c a l c a r e o f f e r e d to infants b o r n prematurely. It is therefore ap p r o p r iat e to revise t he recommendations c o n c e r n i n g n u t r i t i o n fo r preterm infants. A s u b c o m m i t t e e of the Nutrition Comm i t t e e o f t h e C P S w as f o r m e d t o r e v i e w t h e r e c e n t l i t e r a t u r e on n u t r i e n t m e t a b o l i s m an d f e e d i n g o f p r e m a t u r e i n f a n t s and t o make n e w n u t r i t i o n r e c o m m e n d a t i o n s . The s u b c o m m i t t e e i n c l u d e d n e o n a t o l o g i s t s , c l i n i c a l n ut r i t i o n i s t s an d d i e t i t i a n s .
METHODS F o r most n u t r i e n t s it w as i m p o s s i b l e t o d e r i v e r e c o m mendations through t h e u s e o f e s t a b l i s h e d r e s e a r c h methods for d e f i n i n g nutrient r e q u i r e m e n t s i.e., factori a l a n a l y s e s , i n f o r m a t i o n on n u t r i e n t b a l a n c e s , c o n t r o l l e d s t u d i e s and e p i d e m i o l o g i c d a t a ) b e c a u s e t he d at a s i m p l y do n o t e xist . F o r t e r m i n f a n t s , mother's m i l k is the go ld s t a n d a r d fo r n u t r i e n t r e q u i r e m e n t s . However, it is n o t 1766
C AN M E D ASSOC J * l e r J UI N 1 9 9 5 ; 1 5 2 ( 1 1 )
t h e r e f e r e n c e s t a n d a r d fo r n ut ri e nt s f or p r e m a t u r e i n f a n t s b e c a u s e o f t h e r i s k o f i n a d e q u a t e g row t h a n d n u t r i e n t d ef i c i en c i es w h e n m o th er 's m i l k is u s e d w i t h o u t f o r t i f i c a tion. Th e committee t h e r e fo r e had t o fi n d a different method to establish nutrition r e c o m m e n d a t i o n s . Specific outcome g o a l s were p r e d e t e r m i n e d on t h e b a s i s o f t h e infant's b i rth weight and a g e after birth. Tw o birthw e i g h t c a t e g o r i e s ( b e l o w 1000 g an d 1000 g o r more) and t h r e e a g e c a t e g o r i e s (birth t o 7 d a y s , o r t h e t r a n s i tion period; stabilization to discharge f r o m the n e o n a t a l intensiv e c a r e unit (NICU), o r t he s t a b l e - g r o w i n g period; and 1 y e a r f o l l o w i n g d i s c h a r g e f r o m t h e N I C U , o r t h e p o s t d i s c h a r g e p e r i o d ) were d e f ine d . Th e birthw e i g h t categories reflect the difference i n accretion o f n u t r i e n t s b e f o r e b i r t h , and t h e p o s t n a t a l p e r i o d s reflect t h e c h a n g i n g g rroo w t h a n d n u t r i e n t m e t a b o l i s m t h a t a c company postnatal maturation. During t h e t r a n s i t i o n p e r i o d , i n f a n t s ( p a r t i c u l a r l y t h o s e w i t h a birth w e i g h t below 1 0 0 0 g) a re likely t o be c l i n i c a l l y an d m e t a b o l i c a l l y u n s t a b l e an d to l o s e w e i g h t , p r i m a r i l y a s a result o f s h i f t s in w a t e r b a l a n c e and relativ e s t a r v a t i o n . Th e m i n i m u m a c h i e v a b l e g o a l during
t h i s p e r i o d i s t h e p r o v i s i o n o f s u f f i c i e n t n u t ri en ts , p a re n t e r a l l y o r e n t e r a l l y ( by t u be t h r o u g h t h e gastrointestin a l t r a c t ) , t o p r e v e n t n u t r i e n t d e f i c i e n c i e s and s u b s t r a t e cat ab o lis m . If the infant is stable, h i g h e r intakes c a n b e p r o v i d e d during the later part of the transition period. The s t a b l e - g r o w i n g p e r i o d b e g i n s w h e n t h e infant is m e t a b o l i c a l l y and clinically stab le and e n d s w h e n t h e i n f ant is d i s c h a r g e d f r o m t h e N I C U . During this p e r i o d t h e primary n u t r i t i o n a l g o a l i s g row t h a n d n u t r i e n t r e t e n t i o n rates s im il ar t o t h o s e t h a t wo uld h a v e been a c h i e v e d in u t e r o . A c c o r d i n g t o Lubchenco and associa t e s , 2 b et we en 24 an d 3 6 w e e k s o f g es ta t io n , a fe t u s w h o grows at a rate a t t h e 5 0 t h p e r c e n t i l e g a i n s 1 4 . 5 g / k g p e r day. T h i s means that a 1 kg infant n e e d s to g a i n 1 4 . 5 g p e r d ay t o grow a s if i n u t e r o . A n i n f a n t growing a t a r a t e at t h e 9 0 t h p e r c e n t i l e grows 1 2 . 2 g / k g p e r d a y ; fo r a n i n fant at t h e 1 O t h percentile, t h e rate o f weight g a i n is 1 5 . 6 g / k g p e r day . During t he p o s td i s ch a rg e p e r i o d t h e g o a l is a n u t r i e n t i n t a k e t h at is adequate t o a c h i e v e c a t c h - u p g r o w t h . E s t ablis h ing r e c o m m e n d a t i o n s fo r this p e r i o d w as hampered by a marked l a c k o f r e s e a r c h. Th e nutrient i n t a k e n e e d e d to a c h i e v e t h e s e outcome goals is called the preterm recommended nutrient intake w as If e( sP t- aRbN lIi )s .h a Pt -h Re Nr Ie , a ' b ie ns at d ees qtuiam ta et e i nf of ro rsma af te ti oy n a na vda ie lfafbilcea c ty o w as m a d e . These e s t i m a t e s were b a s e d on t h e e s t i m a t e d n u t ri e n t i n ta ke from p r e t e r m - m o t h e r ' s m i l k ( m i l k p r o duced by t h e mother o f a p r e t e r m i n f a n t for h e r ow n i n f a n t , as d is t ing u is h e d f r o m banked human milk ) fe d to t he i n f a n t a t r e c o m m e n d e d v o l u m e s an d on a v a i l a b l e c l i n i c a l s t u d i e s o f e f f i c a c y . On t h e b a s i s o f t he P-RNI f o r e a c h n u t r i e n t , t h e a d e q u a c y o f p r e t e r m - m o t h e r ' s m i l k an d o f f o r m u l a d e s i g n e d f o r p r e m a t u r e inf ants w as d e t e r m i n e d . Fe w s t u d i e s h a v e examined t h e l o n g - t e r m outcomes among infants fed w i t h different nutrient sources o r fed via different routes. Therefore, estimates o f need were b a s e d m a i n l y on s h o r t - t e r m o u t c o m e s . Th e e v i d e n c e i n cluded m u c h more i n f o r m a t i o n on l o w - b i r t h - w e i g h t ( g r e a t e r t h a n 1000 g ) i n f a n t s t h a n on t h o s e w i t h e x t r e m e l y l ow b i r t h w e i g h t s ( l e s s t h a n 7 50 g ) . T h u s , f o r m a n y nutrients, e s t i m a t e s o f t he i n t a k e r e q u i r e d b y i n fa n t s w i t h e x t r e m e l y l o w birth weigh ts were extrapolated f r o m
d a t a i n v o l v i n g l a r g e r p r e m a t u r e i n f a n t s . T h e r e fo r e , recomm e n d a t i o n s f o r these infants a re more tentative t h a n t h o s e fo r l a r g e r i n f a n t s . As more d a t a on i n f a n t s w i t h e x t r e m e l y l ow b i r t h w e i g h t s a r e c o l l e c t e d , t h e s t r e n g t h o f f u t u r e r e c ommendations f or n u tr i e nt i n t a k e will l i k e l y i m p r o v e . Tthe first s e c t i o n o f this a r t i c l e p r o v i d e s a brief discuss i o n o f t h e i m p o r t a n c e o f each nutrient, f o l l o w e d by specif ic recommendations fo r a c h i e v i n g an a d e q u a t e in t a k e f r o m p r e t e r m - m o t h e r ' s m i l k , f o r m u l a an d p a r e n t e r a l nutritio n. Th e second s e c t i o n p r o v i d e s t h e o p t i o n s fo r f ee di n g p r e te r m infants. These guidelines are i n t e n d e d to assist h e alt h c a r e
professionals i n making i n f o r m e d d ec i s i on s a b o u t infant f o o d s and f e e d i n g , t o p r o v i d e background i n f o r m a t i o n fo r r e g u l a t i o n o f i n f a n t f o o d s , and t o s t i m u l a t e t h e i n f a n t - f o o d i n du st ry t o c o n t i n u e t o m a n u f a c t u r e p r o d u c t s t h a t m e e t t h e n e e d s o f premature i n f a n t s . W h e n e v e r p o s s i b l e , t h e e v i d e n c e s u p p o r t i n g recommendations w as weighed in f a v o u r o f randomized c o n t r o l l e d trials. If s u c h trials were u n a v a i l a b l e , c o h o r t studies were c o n s i d ered. If b o t h t y p e s o f s t u d y were unavailable, p u b l i s h e d d a t a were r e v i e w e d an d recommendations were b a s e d on c o n s e n s u s o p i n i o n . Th e recommendations a r e in line w i t h , b u t n o t i d e n t i c a l t o , r e c e n t g u i d e l i n e s from t h e Committee on N u t r i t i o n o f t h e American A c a d e m y o f P e d i a t r i c s an d t h e C o m m i t t e e on N u t r i t i o n o f t h e P r e t e r m I n f a n t o f t h e European S o c i e t y o f P a e d i a t r i c G a s t r o e n t e r o l o g y and N u t r i t i o n . 3 4
RECOMMENDATIONS CONCERNING N U T R I E N T S P-RNIs e s t a b l i s h e d b y t h e c ommi t t ee a r e g i v e n i n T a b l e 1.
WATER W a t e r i n t a k e must m a i n t a i n normal f l u i d an d e l e c -
trolyte balances, through renal excretion of metabolic w a s t e s and r e p l a c e m e n t o f w a t e r lost t h r o u g h t h e s k i n an d t h e r e s p i r a t o r y and d i g e s t i v e t r a c t s , and meet t h e need for g r o w t h . A c h i e v i n g t h e s e g o a l s is c o m p l i c a t e d by t he i m m a t u r i t y o f h o m e o s t a t i c mechanisms in pret e r m infants, b y any c o e x i s t i n g illnesses an d b y nonphysiologic environmental conditions.56 During t h e t r a n s i t i on p e r i o d , p r e t e r m inf ants a r e c l i n i c a l l y u n s t a b l e , and d ev i ce s o r i n t e r v e n t i o n s t h a t affect w a t e r b a l a n c e (e.g., warming the infant w i t h a radiant h e a t e r ) a r e f r e q u e n t l y u s e d . T h e r e f o r e , water r e q u i r e ments must b e d e t e r m i n e d fo r e a c h i n f a n t , an d a s t a n d a r d recommendation cannot be made. I n t h e results o f t w o randomized c l i n i c a l t r ia l s, h i g h - v o l u m e w a t e r i n t a k e w as a s s o c i a t e d w i t h a n i n c r e a s e d r i s k o f p a t e n t d u c t u s a r t e r i o s u s . 7 8 H o w e v e r , i n t a k e must b e sufficient t o p r e v e n t d e h y d r a t i o n . C a r e f u l m o n i t o r i n g o f water i n t a k e and o u t p u t as w e l l a s at l e a s t on e d a i l y w e i g h t measurement and e le ct r o ly t e a s s e s s m e n t a r e n e e d e d . D u r i n g t h e stab l e - g r o w i n g p e r i o d , we r e c o m m e n d i n t a k e w i t h i n a r a n g e (s e e T a b l e 1 ) b e c a u s e o f t h e w i d e v a r i a t i o n in w ater n e e d s fo r infants o f different g es ta ti on a l an d p o s t n a tal a g e s and o f v a r y i n g clinical c i r c u m s t a n c e s . Th e r a n g e i s b as e d on t h e a s s u m p t i o n s t h a t t h e i n f a n t i s s t a b l e , n ot e x p o s e d t o a r a d i a n t h e a t e r , h e a t s h i e l d or c e l l o p h a n e w r a p a n d i s n ot g i v e n p h o t o t h e r a p y . I n f a n t s who a r e s m a l l for their gestational a g e lose l e s s water t h r o u g h t he s k i n t h a n i n f a n t s w h o a r e an a p p r o p r i a t e s i z e f o r t h e i r C AN M E D ASSOC J
o
JUNE 1,
1995; 152 (11)
1767
g e s t a t i o n a l a g e . T h e r e f o r e , t h e f o r m e r group m a y have l o w e r w a t e r n e e d s . Although f e e d i n g a n infant in this p e r i o d 1 2 0 m l i k g p e r d ay o f p r e t e r m - m o t h e r ' s m i l k o r f o r m u l a m a y m e e t fl u i d n e e d s , it is t o o l ow a v olume t o me e t P-RNIs fo r some n u t r i e n t s ( T a b l e 2 ) . During t h e p o s t d i s c h a r g e p e r i o d , water needs a r e assumed t o be equivalent to those for t e r m infants (Table 1). r F a b l e 1 : Recommended n u t r i e n t
1768
intakes f o r premature
C AN M E D ASSOC J * l e r J U I N 1 9 9 5 ; 1 5 2 ( 1 1 )
EN[ERGY
Growth is v e r y r a p i d d u r i n g the third trimester o f gestation, and total e n e r g y n e e d s a r e v e r y h i g h . I n f a n t s i n utero g a i n 1 2 to 1 6 g / k g p e r day.2 Energy e x p e n d i t u r e duri n g this p e r i o d v a r i e s w i d e l y , d e p e n d i n g on c o n d i t i o n s and d i s e a s e s a f f e c t i n g t h e i n f a n t . Energy e x p e n d i t u r e by
infants (P-RNk
I
infants c a n be d i v i d e d into f our categories: the resting m e t a b o l i c rate ( 1 9 6 t o 217 k J / k g [ 4 7 t o 5 2 k c a l / k g ] p e r day); the rate d u r i n g activity (1 3 to 1 7 kJ/kg [3 to 4 kcal/kg] p e r day); the loss o f e n e r g y t h r o u g h excretion ( 4 6 t o 74 k J / k g [ i 1 t o 1 8 k c a l / k g ] p e r d a y ) ; and t h e e n e r g y c o s t o f w e i g h t g a i n ( 1 3 to 1 7 kJ [ 3 to 4 kcal] p e r gram o f w e i g h t gained).'9 Therefore, required e n e r g y intake varies
w i d e l y d e p e n d i n g on t he g o a l fo r w e i g h t g a i n ; i t is b e t w e e n 209 an d 250 k J/ kg ( 5 0 t o 6 0 k c a l / k g ) p e r d a y f o r a n i n f a n t f e d p a r e n t e r a l l y w h o i s n o t g r o w i n g a n d i s i n a t heh e r m o n e u t r a l e n v i r o n m e n t ; h o w e v e r , i t is 5 4 2 t o 584 k J / k g ( 1 3 0 t o 1 4 0 k c a l / k g ) p e r d ay fo r a n i n f a n t growing a t a ' c a t c h - u p rate ( f a s t e r t h a n a n intrauterine growth r a t e ) . I n f a n t s f ed p ar en t er a ll y have l o w e r t o t a l e n e r g y n e e d s
Table 1 continued
P e r i o d after birth; P-RN p e r (stabilization to d i s c h a r g e from
Postdischarge (1 year following d is ch arg e from NICU)
Volume of p r e t e r mm oth er's milk needed to meet P-RN d u r i n g stable-growi ng p e r i o d , m L U k g p e r d ay
7.7-12.3
15.0 ( e s t i m a t e )
120-190
Stable-growing
Transition (birth to 7 days)
N utrient
Zinc, pmol/kg Copper,t¶
6.5
pmol/kg
Selenium,t¶
pmol/kg nmol/kg
Chromium,t¶
Manganese,tjl
nmol/kg
1.1-1.9**
1.1-1.9
115-200
1.1-1.9**
0.04-0.06
0.04-0.06
0.04-0.06
1.0-1.9
1.0-1.9
1.0-1.9
10-20
10-20
10-20
120-200
2.0-4.0
2.0-4.0
2.0-4.0
120-200
0.20
0.25-0.50
0.25-0.50
190-375
40 0 (800 for
40 0
NA
45 0 (birth weight < 1000 g ) 200-450 (birth weight
40 0 p g
NA
0.5**
120-200
2 0 mg
120-200
nmol/kg
Molybdenum,t¶
NICU*)
d ay
l o d i n e , t ¶ pmol/kg
120-200 12
2
Vitamins Vitamin D ,
IU
40-120 (birth weight
1000 g)
4 0 - 260 (birth weight > 1000 g ) Vitamin
A, pg/kg
45 0
certain infants; se e t e x t )
>
g;
1
lower i n t a k e f o r larger infants)
V i t a m i n E, m g / k g Vitamin C , mg/kg
0.5-0.9
6-10
0.5-0.9 6-10
Bi, mg/kg
0.04-0.05
0.04-0.05
0.05
120-200
Vitamin B2, mg/kg
0.36-0.46
0.36-0.46
0.05
NA
0.015
0.015
120-200
0.15
0.15
0.15
120-200
Ni a c i n , NEtt/5000 kJ
8.6
8.6
8.6
120-200
FoIate,
50
50
25
NA
1. 5
1. 5
1. 5
120-200
0.8-1.3
120-200
Vitamin
Vitamin
B6, mg/g o f p r o t e i n
Vitamin B,,
pg
pg
B i o t i n , pg/kg Pantothenic
acid, mg/kg
0.8-1.3
0.8-1.3
tt e ed d fr ro o m p a r e n t e r a l n u t r i t i o n d u r i n g t he t ra n si t i o n p e r i o d . ¶ M a y b e o mmii tt * * F o r i n f a n t s f e d f o r m u l a , t h i s a m o u n t ma y d i f f e r ; se e d i s c u s s i o n i n t e x t .
ttNE
=
niacin equivalents.
C AN M E D ASSOC J
*
JUNE 1 ,
1995; 152 (11)
1769
l a b I e 2 : i n t a k e f r v o m p r e t e r m - r n o t h t . r m e) i l k f 3 2 0 2 0 ( : m L / f k g
1770
C AN M E D ASSOC J * l e , J UI N 1 9 9 5 ; 1 5 2 ( 1 1 )
pe r
d a y ) a l o n e , an d in c o m bi n ati o n w i t h comnmerr:i l f o r t i f i e r S
than those fed enterally b ec a u s e of l o w e r e n e r g y losses i n s t o o l s a n d , p o s s i b l y , more e f f i c i e n t u s e o f e n e r g y . 2 0 During t h e transition p e r i o d , w e i g h t g a i n is u n l i k e l y . I n faf a n t s l o s e u p t o 1 5 o f b o d y w e i g h t d u r i n g t h i s p e r i o d . Th e m a i n t e n a n c e energy i n t a k e i s 209 t o 250 k J / k g ( 5 0 t o 6 0 k c a l / k g ) p e r d ay if t h e i n f a n t i s t o t a l l y p a r e n t e r a l l y f e d and h i g h e r if t h e infant is f e d e n t e r a l l y ( Table 1). If t he infant is m e t a b o l i c a l l y stable, a n e n e r g y i n t a k e h i g h e r t h a n t h e P-RNI m a y b e a c h i e v e d . During
intrauterti nh ee rs attae b lo fe - 1g 2r o tw oi n 1g 6 p ge /r ki og d ,p e wr e di ga hy t c ga an i nb e a tr et ah se o n a b l y e x p e c t e d w i t h t h e r e co m m e nd e d e n e r g y i n t a k e . 2 S i n c e t he mean gross (metabolizable) e n e r g y c o n t e n t o f pretermm o t h e r ' s m i l k is a b o u t 3046 k J / L ( 7 5 0 k c a l / L ) after t h e s e c o n d w e e k o f l i f e 9,21 a n i n t a k e o f 1 4 5 t o 1 8 5 ml i k g p e r d ay i s n e e d e d . If t h e i n f a n t i s f e d p a r e n t e r a l l y , e n e r g y n e e d s a r e 334 t o 4 59 k J/ kg ( 8 0 t o 1 1 0 k c a l l k g ) p e r d a y . 2 O During t h e p o s t d i s c h a r g e p e r i o d , growth rates e q u i v a le nt t o t h o s e o f t e r m i n f a n t s o r g r e a t e r c a n be a c h i e v e d w i t h the recommended e n e r g y intakes, unless the infant ha s u n u s u a l l y h i g h c o n t i n u i n g e n e r g y n e e d s as a result o f a n illness such as chronic lung disease of infancy.22 PROTEIN
P r e t e r m infants grow at similar rates d e s p it e v a r y i n g protein intake, as l o n g as e n e r g y intake d o e s n o t limit growth.2023 However, p r e m a t u r e infants are m e t a b o l i c a l l y i m m a t u r e ; t h e r e f o r e , p r o t e i n t u r n o v e r is h i g h 2 4 an d t h e endogenous synthesis o f certain amino acids is d e l a y e d d u r i n g t h e fir st months o f life. 9 7 T h i s m e t a b o l i c immaturity affects the q u a n t i t y o f protein as well as the bala n c e o f amino acid s r e q u i r e d by i n f a n t s . A g o a l in p r o viding protein is o p t i ma l nitrogen retention, often defined as equivalent to the intrauterine protein gain of a n o r m a l fetus w i t h o u t m e t a b o l i c st r e ss, s u c h as u r e m i a o r distorted b l o o d a m i n o - a c i d patterns. 3 28 Recently, however, it h a s been s u g g e s t e d that o p t i m a l n e u r o d e v e l o p m e n t a l outcome may be an equally i m p o r t a n t g o a l . 2 9 During t h e t r a n s i t i o n p e r io d , p r o t e i n ( a m i n o - a c i d ) int ak e s h o u l d be sufficient to p r e v e n t breakdown o f e n d o g e n o u s tissue; that is, a pproxi ma tel y 1.5 g/kg per day.24 If t he infant is stable d u r i n g t he la t t e r part o f the transit i o n period, h i g h e r amounts o f p r o t e i n ( a m i n o a c i d s ) may be given with safety. D u ri n g the stable-growing p eri od, t h e g o a l i s t o p r o v i d e t h e p r o t e i n i n t a k e n e e d e d to a c h i e v e i n t r a u t e r i n e a c c r e t i o n . I n inf ants with a b i r t h w e i g h t l o w e r t h a n 1 0 0 0 g , t hi s g o a l can be a c h i e v e d w i t h the P - R N I , as l o n g as the e n e r g y intake is adequate. In infants fed p a r e n t e r a l l y , a r a n g e o f 2. 7 to 3.5 g / k g p e r d a y is r e c o m m e n d e d . P r e t e r m - m o t h e r ' s m i l k h a s ta h me e a n p r o t ei in naverage concentration of 16 to 18 g/L;9 2 hence, t a k e v o l u m e s o f m i l k m a y n ot m e e t t h e g o a l s f o r p r o t e i n intake.26,30 A p r o t e i n s u p p l e m e n t to augment p r e t e r m -
mo t h e r ' s m i l k is therefore recommended ( T able 2 ). Th e recommended p o s t d i s c h a r g e p r o t e i n i n t a k e is b a s e d on t h e C a n a d i a n RNI fo r t e r m n e w b o r n s . F o r p r e m a ture infants w h o are g r o w i n g rapidly d u r i n g thi s period, higher intakes are acceptable to achieve catch-up growth.,, Clinical trials h a v e n o t p r o v e d that taurine is a n essent i a l co m p o ne nt o f n ut ri ti o n fo r n e w b o r n s ; h o w e v e r , t a u rine is f o u n d i n h i g h c o n c e n t r a t i o n s i n human milk. All f o r m u l a s b a s e d on c o w ' s m i l k a re c u r r e n t l y s u p p l e m e n t e d should not exceed Such wt hi et ht a tu ar ui rn ie n ec .o n t e n t o sf u hp up lmeam ne nm ti al tk i (o n0 . 2 5 t o 0 . 7 5 m m o l / L ) . The u s e o f f o r m u l a s c o n t a i n i n g n u c l e o t i d e s u p p l e ments h a s n o t been shown to i m p r o v e r e s i s t a n c e a g a i n s t infections in prem ature infants;32 therefore, addition of nu cle o t id e s to f o r m u l a s for p r e m a t u r e infants is n o t recommended. FAT
Fa t , is t he m a j o r s o u r c e o f dietary e n e r g y for p r e m a t u r e i n f a n t s , an d it c o n s t i t u t e s 4 0 t o 6 0 o f t h e e n e r g y in h u m a n m i l k and i n f a n t f o r m u l a s . O x i d a t i o n o f f a t p r o -
v i d e s e n e r g y t o s u p p o r t b a s a l m e t a b o l i c f u n c t i o n s and t o
t h e e n e r g y costs o f tissue synthesis. Th e amount o f f a t r e q u i r e d by p r e m a t u r e infants is d e t e r m i n e d by t he e n e r g y r e q u i r e m e n t , t h e limits to t he amounts o f p r o t e i n and c a r b o h y d r a t e s t h a t c a n b e f e d t o t h e i n f a n t , and t h e volume o f f o o d t he infant c a n eat.33 Essential fatty a c i d s w6 a n d w 3 a r e n e e d e d f o r c e l l - m e m b r a n e f u n c t i o n , meet
e i c o s a n o i d m e t a b o l i s m an d c e n t r a l - n e r v o u s - s y s t e m d e velopment.34 Hence, the recommended fat r e q u i r e m e n t s a r e b a s e d on t h e amount needed t o e n s u r e a d e q u a t e e n e r g y i n t a k e fo r a p p r o p r i a t e g r o w t h and t h e amount o f w 3 an d w6 e s s e n t i a l f a t t y a c i d s n e e d e d f o r o p t i m a l t i s s u e f a t t y - a c i d c o m p o s i t i o n and f u n c t i o n . D u r i n g the transition period, providing a source of fat that includes the e s s e n t i a l f a t t y acids is critical. B i o c h e m i cal indices of essential-fatty-acid deficiency are common in p r e m a t u r e infants 2 to 3 d a y s o l d w i t h birth weights of l e s s t h a n 1250 g . 3 3 5 During t h e s t a b l e - g r o w i n g p e r i o d , t h e recommended t o t a l f a t i n t a k e is b a s e d on t h e f a t c o n t e n t o f h u m a n m i l k . 3 6 I n t a k e o f l i n o l e i c an d l i n o l e n i c a c i d s s h o u l d b e t h e same a s d u r i n g t h e t r a n s i t i o n period. F o r i n f a n t s f e d p a r e n t e r a l l y , f a t i n t a k e m a y c o m p r i s e 20 t o 45 o f t h e t o t a l e n e r g y i n t a k e . L i t t l e i s k n o w n a b o u t t h e fat needs of preterm infants during the postdischarge period. T h e r e f o r e , t h e recommendation is identical t o t h a t during the stable-growing period. Lipid composition
Long-chain fatty acids There is n o definitive
information that arachidonic acid
CA N M ED ASSOC J * JUNE 1, 19 9 5 ; 152 (11)
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( 2 0 : 4 w 6 ) an d d o c o s a h e x a e n o i c a c i d ( 2 2 : 6 w 3 ) a r e e ss en t ia l dietary nutrients at a n y period of d e v e l o p m e n t . H o w e v e r , a n e x o g e n o u s s o u r c e o f t h e s e f at ty a c i ds , c o n s t i t u t i n g 0.25 o f t o t a l e n e r g y intake, is l i k e l y n e e d e d . A l t h o u g h several sources o f these f a t t y acids (such as fish oils) may b e a v a i l a b l e , their l o n g - t e r m safety and efficacy in i n fa n t nutrition ha s n o t been determined.37-3 B e c a u s e suitable s o u r c e s o f o i l s h a v e n o t b e e n a d e q u a t e l y t e s t e d an d i n a p propriate s u p p l e m e n t a t i o n a p p e a r s to present r ea l r is ks o f
gestational a g e is o n l y 30 o f adult a c t i v i t y . 4 5 Salivary and m a m m a r y a m y l a s e s , a l o n g w i t h s m a l l - i n t e s t i n a l gluc o a m y l a s e , p a r t l y compensate f o r t h e r e l a t i v e d e f i c i e n c y o f p a nc r ea t ic a m y l a s e , t h e r e b y a l l o w i n g p r e m a t u r e infants to digest a-glucosides better t h an lactose.44,45 Alt h o u g h , theoretically, l a c t o s e d i g e s t i o n should be l i m it e d , there is no e v i d e n c e o f clinical intolerance among t he s e i n f a n t s . 4 6 4 7 However, t h e r e a re o t h e r r e a s o n s for a d d i n g g l u c o s e p o l y m e r s to formulas: t h e y may result in
recomw e cannot make md ee ln edt ae tr ii oo un ss ef fo fre ci tn sc ,l u s i o n o f t h e s e f a t t y aa nc iy d ss p ien c if fo ir cm u l a s .
and df ae sn ts eirt yg aws it tr hi co u et m ap tc yo ir nr ge ,s p o n d i nt gh e r yi s em ai ny o si mn oclrael ai st ey . c a l o r i c H e n c e , despite these theoretic considerations, there is n o p r o o f t ha t l a ct os e s h o u l d be r e p l a c e d b y g l u c o s e p o l y m e r s in f orm ulas for p r e t e r m infants to i m p r o v e carbohydrate absorption. Nevertheless, to ensure that the o s m o l a l i t y o f f o r m u l a is c l o s e to tha t o f h uman milk, some l a c t o s e may need to be r e p l a c e d by g l u c o s e p o l y mers in f o r m u l a s w i t h h i g h e n e r g y an d m i n e r a l c o n t e n t . During t h e transition p e r i o d , t h e serum g l u c o s e c o n centration in infants s h o u l d b e carefully m o n i t o r e d . I n fants w h o are s mall for their gestational a g e o r w h o w e i g h l e s s t h a n 1000 g a r e p a r t i c u l a r l y v u l n e r a b l e t o h y p o g l y c e m i a and h y p e r g l y c e m i a d u r i n g t h e fi rs t d a y s o f life. In parenteral nutrition, c a r b o h y d r a t e (as g l u c os e) s h o u l d be s u p p l i e d at a rate that a l l o w s t he infant to re ma in e u g l yc e mi c ( T a b l e 1 ) . 4 8 4 9 T h e u s e o f l a c t o s e c o n t a i n i n g milks s h o u l d n o t b e restricted duri n g thi s per i o d . During t h e s t a b l e - g r o w i n g p e r i o d , c a r b o h y d r a t e i n t a k e s h o u l d b e 35 t o 5 0 o f t o t a l e n e r g y intake. Th e recommended c a r b o h y d r a t e i n t a k e is b a s e d on t h e l a c tose c o n t e n t o f human milk. C a r b o h y d r a t e may be g i v e n in the f o r m o f lactose, g l u c o s e p o l y m e r s o r both. F o r i n fants fed parenterally, g l u c o s e s h o u l d c o m p r i s e 50 to 6 0 o f t o t a l e n e r g y intake. Th e recommendation fo r carb o h y d r a t e intake d u r i n g the p o s t d i s c h a r g e p e r i o d is identical to that during the stable-growing period.
Medium-chain triglycerides (MCTs) MCTs u s u a l l y c o n s t i t u t e o n l y 1 t o 2 o f f a t t y a c i d s in human milk.36 Results of r e c e n t studies show that g r o w t h i s n o t i m p r o v e d w i t h t h e u s e o f MCTs a n d d o n o t s up po rt its rou ti n e u s e in formula.40 T h e r e fo r e , the amount in f o r m u l a s h o u l d a p p r o x i m a t e that found in h u m a n m i l k w i t h o u t compromising t o t a l f a t a b s o r p t i o n o r
n e c e s s i t a t i n g t h e u s e o f large amounts o f linoleic acid. Nutrients involved in f at m e t a b o l i s m Inositol
Th e need to i n c l u d e t h i s n u t r i e n t in parenteral o r e n -
t e r a l f o r m u l a t i o n s cannot b e c o n f i r m e d . I n o s i t o l c an b e s y n t h e s i z e d e n d o g e n o u s l y , and i n o s i t o l d e f i c i e n c y in p r e m a t u r e infants ha s n ot been found.4 Choline
Choline can be synthesized endogenously from prot e i n an d is f o u n d i n mammalian m i l k . There is n o d o c u m e n t a t i o n o f c h o l i n e deficiency in p r e m a t u r e infants; t h e r e f o r e , t he a dd it io n o f c ho l i n e t o f o r m u l a s b a s e d on cow's m i l k o r to human m i l k is unwarranted.42 Likewise, t h e r e i s n o d o c u me me n t a t i o n o f t h e e f f i c a c y o f a d d i n g c h o l i n e t o f o rm u la t io n s u s e d fo r p a r e n t e r a l n u t r i t i on .
C al ci um a n d p h o s p h o r u s
L a c t o s e makes up 4 0 to 50 o f the n o n p r o t e i n e n e r g y in human milk. Most p r e m a t u r e i n f a n t s , e v e n t h o s e f e d 2 0 0 mUkg p e r d ay ( 1 3 . 0 t o 1 5 . 5 g o f l a c t o s e / k g p e r day), c a n tolerate the h i g h intake o f lactose f r o m human m i l k . 4 3 A total c a r b o h y d r a t e intake h i g h e r t h a n 15. 5 g/kg p e r d ay m a y b e a c c e p t a b l e f o r i n f a n t s w h o s e w e i g h t g a i n is p o o r . M a n y f o r m u l a s for p r e t e r m infants n ow i n c l u d e
N e i t h e r p r et e rm - m o th e r' s m i l k a l o n e n o r s t a n d a r d f o r m u l a s p r o v i d e sufficient c a l c i u m and p h o s p h o r u s t o meet t h e p r e d i c t e d n e e d s o f growing p r e m a t u r e i n f a n t s . 5 o 5 Th e u s e o f prolonged t ot a l p a r e n t e r a l n u t r i t i o n , p r e t e r m m oth er' s m i l k o r s ta n da r d f o r mu l a ha s been associated w i t h l ow s e r u m an d u r i n e l e v e l s o f p h o s p h o r u s , h y p e r c a l c i u r i a 1 5 2 e l e v a t e d levels o f a l k a l i n e p h o s p h a t a s e 5 3 an d 1 , 2 5 - d i h y d r o x y v i t a m i n D 3 , 5 4 l ow c o n t e n t o f r a d i a l - b o n e m i n e r a l s (c o m pa r ed w i t h i n t ra u te r i ne s ta n da r ds )5 5 5 6 a n d
gd rl aut ce o. s Te h pe o la cy tm iev ri ts y ao sf ct xh -e gi lr u cp or s ii md aa sr ey s si on u tr hc ee foeft u cs a rr ebaoc hh ye -s at least 7 0 of the activity in adults a t a gestational a g e o f a b o u t 26 t o 3 4 w e e k s , w h e r e a s l a c t a s e activity a t that
af vr aa ic lt au br le es sat nu dd i er si cokfe tt sh ei nc asl oc mi uem i an nf adn t ps h. 5o 7 s pAh o cr oun ss en ne se ud ss oo ff p r e m a t u r e infants is that f e e d i n g s c o n t a i n i n g a b o u t 20 t o 30 m m o l / L o f c a l c i u m a n d 1 6 t o 2 0 mmoUL o f p h o s p h o -
CARBOHYDRATE
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RECOMMEN DA r i O N S CONCERN I N G M I N E R A L S
C AN M E D A S S O C J * l e r J U I N 1 9 9 5 ; 1 5 2 ( 1 1 )
rus a re a p p r o p r i a t e in e a r l y n e o n a t a l life. C a u t i o n must be t a k e n if i nf an ts a r e f e d l a r g e amounts o f c a l c i u m an d p h o s p h o r u s i n c o m b i n a t i o n w it h l oo p diuretics or glucoc o r t i c o i d s , both o f w h i c h c a u s e i n c r e a s e d c a l c i u r i a an d increase the risk of renal calcification.58 Some studies 59 60 bu t n o t all,566 h a v e shown that c a l c iu m an d p h o s p h o r u s s u p p l e m e n t a t i o n a c h i e v e s p o s t n a t a l b o n e - m i n e r a l c o n t e n t consistent w i t h intrauterine accret i o n . S m al l i n cr em e nt s i n b o ne - mi n er a l c o n te n t i n early
e s t i m a t e d to be similar to tha t fo r t e r m infants fed hu man milk. Infants fed preterm-mother's m i l k , which c o n t a i n s 1 . 2 m m o l / L o f m a g n e s i u m , f o r t i f i e d pretermmother's milk, s t a n d a r d f o r m u l a o r f o r m u l a for p r e t e r m infants retain magnesium at o r just below t he p re di c te d intrauterine-retention rate ( 0 . 1 5 mmol/kg p e r day). 68,69 High co nce nt r at io ns of c a l c i u m in f o r m u las for p r e t e r m i n f a n t s an d f o r t i f i e d p r e t e r m - m o t h e r ' s m i l k m a y d e p r e s s m a g n e s i u m a b s o r p t i o n ; j 7 t h e r e f o r e , i n t a k e s from t h e s e
Al i sf e wme al ly, b se oimm ep o pr rt ae nm ta tt uo r le o ni gn -f ta ne tr sm ws ki et lhe t aa l vd ee rv ye l lo op mw e nb ti .r 6t 2h w e i g h t w h o h a v e had l o n g p e r i o d s o f f l u i d r e s t r i c t i o n an d
st oh ua rn c te hs a ts hf oo uu ln dd ic no nu tn fa oi rn t i hf ii eg dh ep rr e at me romu-nm to st h oe fr ' ms amgi nl ke .s i u m During t h e t r a n s i t i on period, t h e i n f a n t s magnesium i n t a k e s h o u l d b e a d e q u a t e to m a i n t a i n t h e n o r m a l serum c o n c e n t r a t i o n o f magnesium If t h e i n f a n t is stable duri ng the later part of the transition period, higher intakes ma y be g i v e n w i t h s a f e t y . During t h e s t a b l e - g r o w i n g p e riod, the intake needed to meet intrauterine accretion, r eg ar dl es s o f b i r t h w e i g h t , c a n be a c h i e v e d w i t h t he u s e of preterm-mother's milk or formula. For prematureinfant formulas that hav e a hi gh c a l c i u m c on ten t the ratio o f calcium t o m a g n e s i u m should be less t h a n 1 1 mmol o f c a l c i u m to I mmol o f magnesium i n o r d e r to maximize a b s o r p t i o n o f magnesium.70 Th e Canadian
an d d i b a s i c s o d i u m o r p o t a s s i u m phosphate) a r e 1 5 mmol/L f o r b o t h c a l c i u m an d p h o s p h o r u s . 6 3 T h i s c o n c e n tration is o n l y attainable w h en the a m i n o - a c i d c o n t e n t of t h e p a r e n t e r a l f o r m u l a t i o n is 25 g / L o r l e s s ; o t h e r w i s e , there is a risk o f c a l c i u m o r p h o s p h o r u s precipitation. During t h e s t a b l e - g r o w i n g p e r i o d , t h e g o a l is t o a c h i e v e i n t r a u t e r i n e c a l c i u m an d p h o s p h o r u s a c c r e t i o n an d bone mineralization. Unfortunately, we c a n n ot yet accurately predict intakes that w i l l a c h i e v e n o r m a l l o n g - t e r m bone
RNI fo r t e r m i n f a n t s 6 s is b a s e d on t h e c o n t e n t o f magnes i u m in human milk; this RNI is likely to be a d e q u a t e for premature infants during the postdischarge period.
t he ra p y w i th calciuric d r u g s may benefit f r o m receiving s u p p l e m e n t s for 2 to 3 months to attain c a t c h - u p bone g r o w t h . Th e amount and d ur at io n o f m in er al s u p p l e m e n t a t i o n an d t h e c o m p l i c a t i o n s o f p r o l o n g e d i n f a n t f e e d i n g w i t h mineral-fortified m i l k require further study. During t h e transition p e r i o d , c a l c i u m and p h o s p h o r u s intake should be adequate to achieve norm al serum conc e n t r a t i o n s o f t he se m in e r al s an d t o p r e v e n t h y pe rc a l c i uria ( T a b l e 1). If t he infant is f e d e x c l u s i v e l y t h r o u g h t o t a l parenteral nutrition, the u p p e r limits o f solubility w i t h a v a i l a b l e s a l t s ( c a l c i u m g l u c o n a t e a n d m i xe d m o n o b a s i c
mineralization. Fo r prem ature infants, regardless of birth w e i g h t , intrauterine bone g r o w t h may be a p p r o x i m a t e d by p r o v i d i n g t h e recommended c a l c i u m and p h o s p h o r u s i n t a k e s .5 9 Th e r e c o m m e n d e d molar r a t i o o f c a l c i u m t o p h o s p h o r u s is 1 .6 to 2.0. F o r infants fed p r e t e r m - m o t h e r ' s milk, this intak e c a n b e a c h i e v e d o n l y t h r o u g h a d d i n g c a l c i u m and p h o s p h o r u s a s i n d i v i d u a l s a l t s o r a s a humanm i l k fortifier64 (T able 2) . Some f o r m u l a s d e s i g n e d for preterm i n f a n t s c o n t a i n t h e a m o u n t s o f c a l c i u m an d p h o s p h o r u s needed to a c h i e v e intrauterine a c c reti o n o f bone m inerals; h o w e v e r , due to v ariations in absorption, a d e q u a t e r e t e n t i o n i s n ot g u a r a n t e e d i n a l l i n f a n t s . T h e r e c o m m e n d e d p o s t d i s c h a r g e i n t a k e o f c a l c i u m and p h o s p h o r u s is b a s e d on t h e c u r r e n t Canadian RNI f o r term infants d u r i n g the first 6 months.65 L o n g - t e r m studies suggest that t he u s e o f fortified f o r m u l a s o r p r e t e r m - m o t h e r ' s milk is a s s o c i a t e d with improved bone-mineral conhe r s t u di e s a r e r e q u i r e d . t e n t , 6 6 , 6 7 b u t f u r t he
Magnesium Th e magnesium r e q u i r e m e n t for p r e m a t u r e infants is
Sodium, chloride a n d potassium
P r e m a t u r e infants g e n e r a l l y require a h i g h e r sodium i n t a k e t h a n t e r m i n fa n t s and a h i g h e r i n t a k e t h a n t h a t s u p plied in human m i l k of m o t h e r s delivered at t e r m (5 to 7 mmoVL) o r in fo r m u l a s d e s i g n e d for t e r m infants (8 to 9 m m o V L ) . 6 9 7 1 7 2 T h e s u p p l y o f c h l o r i d e an d p o t a s s i u m f r o m human milk, h o w e v e r , is generally a d e q u a t e for p r e t e r m infants.
During t h e t r a n s i t i o n p e r i o d , sod iu m an d c h l o r i d e
needs are difficult to predict b ecause of d e v e l o p m e n t a l and c l i n i c a l f actors a ffec ti n g h o m e o s t a s i s o f t he se m i n e r als. The n e e d s o f e a c h infant s h o u l d be assessed to determine if t h e y are h i g h e r o r l o w e r t h a n basal r e q u i r e m e n t s ,
w h i c h can be me t through f e e d i n g with pretermm o t h e r ' s m i l k . 7 2 During t h e s t a b l e - g r o w i n g p e r i o d , h u man m i l k may meet t h e recommended i n t a k e o f sodium and c h l o r i d e if t h e i n f a n t is f e d lar g e volumes ( 1 8 5 t o 200 m L l k g p e r d a y ) . 7 However, c o n c e n t r a t i o n s o f t he se nutrients in human m i l k d e c l i n e after this period, so a supplement m a y be r e q u i r e d . S eru m l e ve l s o f sodium
s h o u l d b e monitored t o d e t e r m i n e t h e ne e d f o r s u p p l e m e n t a t i o n . Estimated p o t a s s i u m r e qu i r e m en t s c an be
with c o n t ati hn rs o u1 g2 h. 5 f te oe d i1 n6 g m m o l / pLr eo tf e rp om t- am so st ih ue mr .' s T mhi el k ,c ownhc ie cn ht r a t i on s o f s o d i u m , c h l o r i d e and p o t a s s i u m in f o r m u l a s d e s i g n e d for p r e m a t u r e infants may exceed t he P - R N I ;
me t
C AN M E D ASSOC J * JUNE 1 ,
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h o w e v e r , there a re no reports o f toxi c effects a s s o c i a t e d with t h e s e levels. During t h e p o s t d i s c h a r g e p e r i o d , s o d i u m , c h l o r i d e and p o t a s s i u m n e e d s a r e l i k e l y s i m i l a r to those of term infants. Iron Th e major r e s e r v e o f i r o n fo r p r e m a t u r e i n f a n t s a t birth is the h e m o g l o b i n mas s ; there is little iron stored in
Instead, there are three acce p t able objectives in setting intake a m o u n t s : p r e v e n t i o n of trace-mineral deficiencies, r e p l e n i s h m e n t o f stores that would n o r m a l l y h a v e been deposi ted in the d e v e l o p i n g fetus d u r i n g the last trim e s t e r , and t h e a v o i d a n c e o f e x c e s s i v e i n t a k e s , w h i c h could have toxic effects. During t h e transitio n p e r i o d , w h e n t h e inf ant is l i k e l y t o b e c l i n i c a l l y u n s t a b l e , i nt a ke s o f t r a c e m i n e r a l s m a y n ot b e n e c e s s a r y , s i n c e d e f i c i e n c i e s a r e u n l i k e l y t o d e -
t h e l i v e r o r t h e s p l e e n . D e s p i t e t h e l ow s t o r e s , i r o n d e f i c i e n c y is unlik ely to p l a y a role in t he anemia o f p r e m a turity d u r i n g t h e fir st 2 months o f life u n l e s s b l o o d w as l o s t d u r i n g birth o r as the result o f p h l e b o t o m i e s to coll e c t s p e c i m e n s fo r l a b o r a t o r y t e s t s , an d t h e l o s t blood was n o t r e p l a c e d t h r o u g h a n e r y t h r o c y t e t r a n s f u s i o n . 7 3 7 4 I n a d d i t i o n , e r y t h r o c y t e s y n t h e s i s is l i m i t e d b y v e r y l ow erythropoietic activity until 5 to 7 weeks a f t e r b i r t h . Prop hy l ac ti c u se o f i r o n s u p p l e m e n t s o r i r o n - fo r t i fi e d f o r mula d u r i n g t h e f i r s t 2 months o f l i f e h a v e no effect on t h e fall in hemoglobin c o n c e n t r a t i o n d u r i n g this p e riod.7576 Once active erythropoiesis begins, h o w e v e r , all prem ature infants require iron to maintain optimal hem o g l o b i n production.7778 During t h e transition p e r io d , t h e r e is no need fo r i r o n . At t h e s t a r t o f t h e s t a b l e - g r o w i n g p e r i o d , i r o n s u p p l e m e n t s are n o t recommended. H o w e v e r , starting 6 to 8 w e e k s a f t e r b i r t h , i n f a n t s w i t h b i r t h w e i g h t s o f 1000 g o r more s h o u l d h a v e t h e i r d i e t s u p p l e m e n t e d w i t h i r o n (2 to 3 mg/kg pe r d a y ) o r b e given fo r mu la c o n t a i n i n g iron (1 2 m g / L ) to prev en t iron-deficiency anemia.77 The i r o n n e e d s o f i n f a n t s w i t h b i r t h w e i g h t s b e l o w 1000 g a re l i k e l y greater. Theref ore, fo r th ese i n f a n t s , a t o t a l inta ke o f 3 to 4 mg/kg p e r d a y starting 6 to 8 weeks after b i r t h is recommended.77 An oral i r o n supplement is needed to a c h i e v e this intake. Iron s u p p l e m e n t a t i o n s h o u l d b e c o n t i n u e d until t he infant is 1 2 months cor-
v el o p d ur i ng s u c h a sh ort period. If trace m i n e r a l s are i n cluded in t h e f e e d i n g regimen o f i n f a n t s d u r i n g this period, the intake should be adequate to prevent defic i e n c y y e t n ot e n o u g h t o c a u s e t o x i c e f f e c t s . I f p a r enteral nutrition is g iv e n d u r i n g the transition period, trace minerals, w i t h the e x ce p t io n of zinc, need n o t b e included. Th e recommended i n ta kes for infants f e d parenterally are in k e e p i n g w i t h t h e r e c e n t recommendat i o n s b y t h e Committee on C l i n i c a l P r a c t i c e I s s u e s o f t h e American S o c i e t y fo r C li ni ca l N u t r i t i o n . 6 3 During t h e s t a b l e - g r o w i n g p e r i o d , w h e n r a p i d growth r e s u m e s , t r a c e m i n e r a l s s h o u l d b e i n c l u d e d in infants' diet at conc e n t r a t i o n s t h a t p r e v e n t d e f i c i e n c i e s or a t t h e h i g h e r c o n c e n t r a t i o n s that also r e p l a c e body stores. Higher int a k e s s h o u l d continue d u r i n g t h e p o st di s ch ar ge p e ri o d w h e n growth is r a p i d and t h e r i s k o f t r a c e - m i n e r a l d e f i ciencies is high.
rt ee rc mt) e. d7 8 a Ag te t(htahte t i in mf ae n ti n sf a an tg es hh ae md o hg el o ob ri ns h ae n db efee nr r i bt oi nr nl e va -t els should b e m o n i t o r e d to ensure adequate h e m a t o l o g i c
Nutritionally essential trace minerals include zinc, c o p p e r , s e l e n i u m , chromium, m a n g a n e s e , m o l y b d e n u m an d i o d i n e . P u b l i s h e d r e p o r t s o f m i n e r a l d e f i c i e n c i e s among p r e m a t u r e infants h a v e i n v o l v e d o n l y si x of these e l e m e n t s . However, inf ants b o r n p r e m a t u r e l y are a t i n c r e a s e d r i s k o f t r ac e -m i ne ra l d e f i c i e n c i e s b e c a u s e o f l ow s t o r e s a t b i r t h , v e r y r a p i d p o s t n a t a l ' g r o w t h and v a r i a b l e
sh taavt eu s f oofu npdr et mh aa tt ut rh ee s ie n fi an nf ta sn t sd u hr ai vn eg at h he a if ri r zs ti nyce al re v eo lf l i f e sign i f i c a n t l y l o w e r t h a n t h a t o f term i n f a n t s . 8 3 8 4 T h i s evidence s u p p o r t s the s u g g e s t io n that a zinc d e f icie ncy limits growth d u r i n g t h e first year. No c a s e s o f a c u t e z i n c d e f i c i e n c y d u r i n g t h e f i r s t w e e k s a f te r b i r t h h a v e b e e n d e s c r i b e d . T h e r e f o r e , d u r i n g the transition period, t he amount o f z inc in human m i l k is likely ad e q u at e . F o r parenteral nutrition, a z inc intake o f 6 . 5 g m o l / k g p e r d ay i s r e c o m m e n d e d . 8 5 During t h e s t a b l e -g r o wi n g period, infants fed preterm-mother's milk h a v e n o t had a z i n c d e f i c i e n c y . O u r recommendation is b a s e d on t h e z i n c c o n t e n t o f p r e t e r m - m o t h e r ' s m i l k , f e d to infants in a d e q u a t e a m o u n t s . B e c a u s e of a postulated
ti nht ea k ge .o7 l9 ,d 8 0 s tTa hn ed a rt dr afco er - rm ei nq eu ri ar le m ce on nt ts e nf ot r ot fe rhm u mi n af ann t sm ,i l pkr o i-s v i d e d th a t t h e y i n gest a n a d e q u a t e volume o f milk.65 However, fo r p r e t e r m infants t h e r e is no g o l d s t a n d a r d .
di ne p r e s s i o n o f z i n c a b s o r p t i o n c a u s e d b y o t h e r m i n e r a l s human-milk fortifiers,59 fortified p r e t e r m - m o t h e r ' s milk an d h i g h - c a l c i u m f o r m u l a s s h o u l d c o n t a i n a d d i tional zinc. During t h e p o s t d i s c h a r g e p e r i o d , z i n c i n t a k e
status.
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C AN M E D ASSOC J * l e, JU IN 1 9 9 5 ; 1 5 2 ( 1 1 )
Zinc Th e z i n c content o f h uma n m i l k cannot be used as a
g o l d s t a n d a r d to establish dietary zinc r e q u i r e m e n t s for preterm infants. In fact, frank zinc deficiency d e v e l o p e d in ma n y b rea s t- f ed p r e t e r m i n f a n t s . 8 8 2 Although s u c h f r a n k d e f i c i e n c y is r a r e , m a ny br e as t - fe d p r e m a t u r e i n f a n t s m a y s u f f e r from a z i n c d e p l e t i o n w i t h o u t s h o w i n g any s i g n s o f d e f i c i e n c y . L o n g i t u d i n a l s t u d i e s o f t h e z i n c
f r o m h uman m i l k may be i n a d e q u a t e to meet t he n e e d s o f a r a p i d l y growing infant.882 An i nta ke o f 1 5 g i m o l / k g p e r d ay s h o u l d m e e t t h e s e n e e d s an d can be a c h i e v e d t h r o u g h t h e u s e o f formulas d e s i g n e d f o r te r m o r preterm infants. B r e a s t - f e d i n f a n t s w o u l d n e e d a z i n c g l u c o n a t e o r z i n c - s u l fa t e supplement o f 7. 5 , u m o l / k g p e r day t o a c h i e v e this intake. However, t h e effect o f z i n c s u p p l e m e n t a t i o n on b r e a s t - f e d p r e t e r m i n f a n t s h a s n o t been studied; thus, a definitive recommendation for z i n c
supplementation
cannot be made.
Copper Copper d e f i c i e n c y h a s been r e p o r t e d in p r e t e r m an d
t e r m infants fed primarily c ow's milk, iron-fortified f o r m u l a , p a s t e u r i z e d h u m a n milk o r a t o t a l - p a r e n t e r a l nutrition f orm ulation that d o es n ot include copper.8989 D e f i c i e n c y h a s n o t o c c u r r e d in infants fe d c u r r e n t form u l a s o r p r e t e r m - m o t h e r ' s milk. Although a c u t e toxic e f f e c t s o f copper a r e r a r e , l o n g - t e r m e x c e s s i v e i n t ak e o r r e duced h e p a t i c e x c r e t i o n c a n result in liver c i r r h o s i s . 9 During t h e t r a n s i t i o n p e r i o d , copper i n t a k e s h o u l d b e equivalent to that p r o v i d e d by human milk. If short-term total parenteral n u t r i t i o n is used, s u p p l e m e n t a t i o n may n o t b e necessary.63 During t h e s t a b l e - g r o w i n g and p o s t d i s c h a r g e p e r i o d s , t h e i n t a k e o f copper f r o m h u m a n m i l k p r e v e n t s d ef ic i en c y . H o w e v e r , b e c a u s e copper a b s o r p t i on may b e d e p r e s s e d by t he large o f amounts o f z i n c 9 f o u n d i n some p r e t e r m f o r m u l a s an d human- milk f o r t i f i e r s , a copper i n t a k e o f 1 . 6 t o 3. 2 g m o l / k g p e r d ay i s recommended for infants, regardless o f birth w e i g h t , fe d f o r t i f i e d human m i l k o r f o r m u l a d e s i g n e d for p r e t e r m inf a n t s . F o r t ho se f e d parenterally, r e c o m m e n d e d i n t a k e s a re 0. 3 g . m o l / k g p e r d a y . 8 5 6 3 Infants with c h ol es ta s i s s h o u l d n o t r e c e i v e copper parenterally, s i n c e b i l i a r y e x c r e t i o n is t he main e x c r e t o r y route. Selenium Although s e l e n i u m d e f i c i e n c y in i n f a n t s is rare, t h e m i n e r a l is r e c o g n i z e d as nutritionally e s s e n t i a l . 9 2 Infants
fed preterm-mother's milk (which contains 0.3 i m o l / L of selenium), s t a n d a r d f o r m u l a for p r e m a t u r e infants ( w h i c h c o n t a i n s 0 . 1 j I m o l / L ) or f o r m u l a f o r p r e m a t u r e i n f a n t s s u p p l e m e n t e d w i t h 0 . 4 g m o l / L o f s e l e n i u m have been s hown t o have s i m i l a r e r y t h r o c y t e selenium and glut a t h i o n e - p e r o x i d a s e c o n c e n t r a t i o n s . There is n o e v i d e n c e o f s e l e n i u m d e ficie ncy among o l d e r p r e t e r m infants. During t h e t r a n s i t i o n p e r i o d , s e l e n i u m i n t a k e s h o u l d be e q u i v a l e n t t o t h a t p r o v i d e d in h u m a n mi l k . Selenium m a y b e o m i t t e d from s o l u t i o n s used i n t o t a l p a r e n t e r a l and
nutrition. During t h e s t a b l e - g r o w i n g postdischarge periods, h o w e v e r , total parenteral nutrition s h o u l d pro-
vide
0.02 t o 0.025
g m o l / k g p e r d a y o f s e le n i um . B e c a u s e
selenium is p r i m a r i l y excreted b y t h e k i dn ey s, t h e amount s h o u l d be lowered if t h e ren a l o u t p u t o f t h e i n fant is decreased.63
Chromium C h r o m i u m d e f i c i e n c y h a s b e e n reported i n t h r e e adult patients receiving l o n g - t e r m total parenteral nutrition that d i d n o t c o nt ai n chromium; h o w e v e r , s u c h defi-
cc ih ernocmy i uh am s h na os t a b ve eerny rleop wo r ot re dd e ri n o fc h ti ol dx ri ec n .e 9f 3f 4e c4 t s T. r9 5i v Ta le ernmt infants fe d their p r et e rm - mo t h er ' s m i l k receive about 1.0 t o 1 . 9 n mol / k g p e r d ay o f c h r o m i u m . 9 5 There is n o i n f o r mation on t h e c h r o m i u m c o n t e n t o f t h e h u m a n m i l k o f m o t h e r s who h a v e d e l i v e r e d p r e t e r m ; h o w e v e r , s i n c e p r e t e r m i n f a n t s f e d t h e i r p r et e rm - mo t h e r ' s m i l k have n o t d e v e l o p e d chromium def iciency, this i n t a k e is likely a d e q u a t e . S im i la rl y, s i n c e i n f a n t s f e d f o r m u l a w i t h h i g h e r c o n c e n t r a t i o n s o f chromium t ha n t ho s e found i n h u m a n m i l k h a v e n o t suffered ov ert toxic e f f e c t s , there is likely a wide r a n g e of safe i n t a k e . 9 5 D u r i n g the transition period, a n intake equivalent to that p r o v i d e d in human m i l k is r e c o m m e n d e d , 9 6 b u t chromium may b e o m i t t e d f r o m solutions for t o t a l parenteral nutrition. Th e same amount is r e c o m m e n d e d d u r i n g t h e s t a b l e growing and p o s t d i s c h a r g e p e r i o d s ; h o w e v e r , total p a r enteral nutritio n s h o u l d p r o v i d e 3.8 n m o l / k g p e r d a y. B e c a u s e chromium is e x c r e t e d by t he k idney s, t he amount s h o u l d b e l o w e r if infants renal o u t p u t is decreased.63 Manganese Manganese deficiency in humans ha s n o t been c o n -
clusively s h o w n ; h owever, the toxic effects of excessive m a n g a n e s e i n a d u l t s h a v e b e e n w e l l d e s c r i b e d . Human m i l k c o n t a i n s a b o u t 0. 1 g i m o l / L o f manganese, and f o r contain c o n c e n t r a t i o n s . There is n o evimd ue ln ac se t h a t t h e lh oi wg h ien rt a k e o f m a n g a n e s e i n i n f a n t s r e c e i v i n g preterm-mother's m i l k is associated w i t h deficiency o r that higher intakes in infants fed formulas are associated with toxic effects.97 During t h e transition p e r i o d , t h e manganese i n t a k e s h o u l d be equivalent to that p r o v i d e d in human milk; manganese ma y be o m i t t e d from s o l u t i o n s fo r total p a r enteral nutrition. T h i s intake is also c o n s i d e r e d ad e q u at e d u r i n g t h e s t a b l e - g r o w i n g an d p o s t d i s c h a r g e p e r i o d s . T o t a l p a r e n t e r a l n u t r i t i o n s h o u l d p r o v i d e 0.02 j m o l / k g p e r d a y o f m a n g a n e s e . M a n g a n e s e sh o u l d b e omi tt ed from t o t a l p a r e n t e r a l n u t r i t i o n g i v e n t o i n f a n t s w i t h h e p atic cholestasis.6398
Molybdenum O n l y on e c a s e o f mol ybden u m d e f i c i e n c y i n an a d u l t
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a n d n on e i n i n f a n t s h a s b e e n r e p o r t e d . 9 9 T h e m o l y b d e n u m c o n c e n t r a t i o n i n t h e b r e a s t m i l k o f mothers d e l i v e r e d a t
t e r m is a b o u t 2.0 nmol/L,'° bu t that o f m o t h e r s delivered p r e t e r m i s u n k n o w n . D u r i n g t h e t r a n s i t i o n p e r i o d , an i n f a n t f e d h u m a n m i l k r ec ei ve s 2 . 0 t o 4 . 0 n m o V k g p e r d a y , which is also c o n s i d e r e d a d e q u a t e d u r i n g t he stableg r o w i n g an d p o s t d i s c h a r g e p e r i o d s . M o l y b d e n u m s u p p l e m e n t a t i o n o f 2. 6 n m o l l k g p e r d a y is recommended o n l y f o r i n f a n ttss n e e d i n g l o n g - t e r m t o t a l p a r e n t e r a l n u t r i t i o n . 6 3 Iodine
I n p r e m a t u r e i n f a n t s , t h e mechanisms that r e g u l a t e iod i n e l e v e l s a re i m m a t u r e . H e n c e , if t h e i n f a n t s diet is de f i c i e n t , t h e inf ant c a n n o t c o m p e n s a t e by r e t a i n i n g more i o d i n e and r e q u i r e s a h i g h e r i o d i n e i n t a k e t o m a i n t a i n a euthyroid state. P r e m a t u r e infants may e xp e r i e n c e transient h y p o t h y r o i d i s m when receiving iod ine intakes of 0.08 to 0 . 2 4 J m o l V k g pe r day. ° If p r e m a t u r e infants o f a g e s t a t i o n a l a g e o f l e s s t h a n 34 w e e k s a r e e x p o s e d t o h i g h amounts o f i od in e (0.8 g m o l p e r d a y o r m o r e ) by c u t a n e o u s administration of iodine solutions, a d e c r e a s e d level o f T 4 ( t e t r a i o d o t h y r o n i n e ) an d a n i n c r e a s e d serum level o f t h y r o i d s ti mu l a ti n g hormone may result. 02 Th e c o n t e n t o f i o d i n e i n h u m a n m i l k v a r i e s , d e p e n d i n g on t h e d i e t a r y i n t a k e o f t h e m o t h e r , b e t w e e n 1 . 1 t o 1 . 4 J m o V L .L F o r m u l a s for p r e t e r m infants c o n t a i n similar amounts.'03 T h u s , a n a v e r a g e intake is a b o u t 0. 2 j m o l / k g p er day. Si n c e breast-fed infants receiving less t ha n 0 . 2 4 imol/kg per d a y h a v e a negative i od i n e balance'04 ( a s s u m i n g they
i o d i n e from i o d i n e - c o n t a i n i n g s k i n c l e a n s e r s ) , s u p p l e m e n t a t i o n is recommended. D u r i n g the transition period, a n intake equivalent to t he amount in human m i l k is recommended. I o d i n e may b e o m i t t e d f r o m solutions for t o t a l parenteral nutrition. D u r i n g t h e s t a b l e - g r o w i n g and p o s t d i s c h a r g e p e r i o d s , if d o n ot absorb
ap l pe rm eetnetr m i s i nn feaen dt e ids bt or e aa sc th i fe ev de e tx hc el u sri ev ec loy m, ma en n di oeddi n ien t sa uk pe -. Neither breast-milk fortifiers n o r c o m m e r c i a l l y available mineral-and-vitamin s u p p l e m e n t s co nt ain iodine. Most inf ants r e c e i v i n g total p a r e n t e r a l n ut ri ti o n a re c l e a n e d w i t h i o d i n e - c o n t a i n i n g d i s i n f e c t a n t s o r d e t e r g e n t s , and on e m a y assume t h a t a s i g n i f i c a n t amount o f i o d i n e is a b s o r b e d t h r o u g h t h e s k i n . On t h e basis o f this a s s u m p t i o n , t h e r e c o m m e n d e d p a re n te r a l i n ta k e o f i o d i n e i s 8 n m o l / k g per day.
early life is t he i n f a n t s v i t a m i n - D status at birth, which is related to maternal intake of vitamin D during pregnancy. Human milk contains only small concentrations o f v i t a m i n D ( 1 0 t o 80 I U L ) , w h e r e a s t h e v i t a m i n - D req u i r e m e n t of p r e m a t u r e infants ha s been e s t imat e d at bet w e e n 4 00 an d 5000 IU p e r d a y . 0 5 - o 0 7 E s t i m a t e s v a r y s o wi d e l y because, in the populations studied, the vitaminD status o f m o t h e r s , and t h u s o f i n f a n t s at b i r t h , dif f ered greatly. P r e ma t u r e infants of a gestational a g e of greater
t h a n 28 w e e k s a p p e a r t o b e a b l e t o h y d r o x y l a t e v i t a m i n D m e t a b o l i t e s a d e q u a t e l y an d t o e l i c i t a n o r m a l p h y s i o l o g i c response t o hypocalcemia an d hypophosp h a t e m i a l 8 as w ell as to a b s o r b a n a d e q u a t e amount o f fat-soluble vitamins. L i t t l e is known a b o u t t he c a p a c i t y o f p r e m a t u r e i n f a n t s w i t h a v e r y l ow b i r t h w e i g h t an d a g e s t a t i o n a l a g e o f l e s s t h a n 28 w e e k s t o a b s o r b o r h y droxylate vitamin D. During t h e t r a n s i t i o n p e r i o d , t h e need t o i n c l u d e v i t a mi n D in f o r m u l a t i o n s fo r total p a r e n t e r a l n u t r i t i o n is u n known. R ecommended total intake o f the v i t a m i n f r o m p a r e n t e r a l an d e n t e r a l f e e d i n g i s 40 t o 120 IU p e r d ay f o r i n f a n t s w i t h a b i r t h w e i g h t o f l e s s t h a n 1000 g an d 4 0 t o 2 6 0 IU p e r d ay f o r i n fa n ts w i t h a b i r t h w e i g h t o f 1000 g o r mor e .6 3 If t he infant is stable d u r i n g t he l a t t e r part o f the transition period, higher intakes o f v i t a m i n D may be used w i t h s a f e t y . During t h e s t a b l e - g r o w i n g p e r i o d , r e ga r dl e ss o f t h e i n f a n t s b i r t h w e i g h t , a v i t a m i n - D i n t a k e o f 4 00 IU p e r d ay i s n e e d e d t o a c h i e v e a n o r m a l ser um c o n c e n t r a t i o n o f 25-OH v i t a m i n D w i t h o u t i n c r e a s i n g t h e r i s k o f t o x i c e f f e c t s . 06 I f t h e i n f a n t i s b l a c k o r o f A s i a n d e s c e n t o r h a s a l ow plasma c o n c e n t r a t i o n o f 25-OH v i t a m i n D ( 1 0 t o 2 0 n g / m L ) , t h e r e c o m m e n d e d v i t a m i n - D i n t a k e is 8 00 IU p e r d a y . F o r m u l a s o r h u m a n m i l k f o r t i f i e r s s h o u l d c o n t a i n 3 00 I U / 4 1 7 kJ ( 3 0 0 I U / 1 0 0 k c a l ) o f v i t a m i n D t o e n s u r e t h a t most i n f a n t s r e c e i v e a d e q u a t e amounts. F o r s m a l l i n f a n t s , v i t a m i n D s u p p l e ments are r e q u i r e d to
During p o s t d i s c h a r g e p e r i o da,c h ti he ev e vtihte as me ia nm -o Du n ti ns t. a k e r e c otmh -e m e n d e d is 4 00 IU p e r d a y . 6 5
Vitamin A Th e r e t i n o l c o n c e n t r a t i o n o f e a r l y m i l k o f mothers
Fat-soluble vitamins
d e l i v e r e d p r e t e r m ( f r o m t h e 6 t h t o t h e 3 7 t h d ay o f l a c t a t i o n ) v a r i e s b u t i s u s u a l l y h i g h e r t h a n t ha t o f m o t h e r s d e l i v e r e d a t t e r m . B o t h r et in o l e s te r an d t o t a l c a r o t e n e c o n centrations in human m i l k decrease d u r i n g the co u r s e o f lactation.15 9 In addition, p ho t o d e g r a d a t i o n of vitamin A may occur in f o r m u l a o r h u m a n m i l k f e d t o i n f a n t s t h r o u g h plastic nasogastric tubes. P r e t e r m infants h a v e
Vitamin D
b e e n s h o w n t o h a v e l ow h e p a t i c s t o r e s o f r e t i n o l a t b i r t h an d l o w e r c o n c e n t r a t i o n s o f p l a s m a retinol an d retinol-
R E C O M M E N D A T I O N S CONCERNING V I T A M I N S
Th e main factor affecting t h e need fo r v i t a m i n D i n 1776
C AN M E D ASSOC J * l e r J U I N 1 9 9 5 ; 1 5 2 ( 1 1 )
binding protein (RBP) than term newborns. Many inf ants have a p l a s m a c o n c e n t r a t i o n o f retinol o f below
0 . 3 5 ,umol/L, which indicates a deficiency. Serum retinol and RB P c o n c e n t r a t i o n s a r e h i g h e r i n i n f a n t s r e c e i v i n g f o r m u l a s d e s i g n e d for p r e t e r m infants t h a n in t h o s e r e ceiving human milk; however, o n l y infants fed formula supplemented w i t h 450 t o 8 40 jig p e r d ay o f r e t i n o l m a i n t a i n serum c o n c e n t r a t i o n s o f r e t i n o l at p r e f e e d i n g lev els. ° ' Th e l a c k o f c l i n i c a l and b i o c h e m i c a l t o x i c e f fects a m o n g i n f a n t s g i v e n a v i t a m i n - A supplement s u g g e s t s t h a t t h i s s u p p l e m e n t r a n g e ( 4 5 0 t o 840 j i g p e r d a y )
to I g total lipids. M i l k f r o m m o t h e r s delivered preterm c o n t a i n s g r e a t e r c o n c e n t r a t i o n s o f v i t a m i n E (4. 5 mg/L) t h a n t h a t from mothers d e l i v e r e d at t e r m . ' 5 H e n c e , p r e t e r m infants fed their ow n mother's m i l k m a in t ai n adeq u at e levels o f v i t a m i n E. 5 D u r i n g the transition period, infants receive parenteral nutrition, which co nt ains multivitamins inclu d ing v it am in E; therefore, no a d d i t i o n a l v i t a m i n E is recommended. A parenteral intake of 2.8 mg/kg per d a y appears to b e ade-
ci so ns ta rf eo l fl oerd ps rt eu td ie er sm h i an vf ae n tbs e. e An lctohnod uugcht es de v te or a dl e rt ae nr dm oi nm ei zt eh de e f f e c t o f r e t i n o l s u p p l e m e n t a t i o n on t h e i n c i d e n c e o f a n d o u t c om om e s f r o m b r o n c h o p u l m o n a r y d y s p l a s i a ( B P D ) , t h e results have b e e n i n c o n c l u s i v e . 5 , , 2 T h e r e f o r e , w e c a n n o t recommend g i v i n g a v i t a m i n - A s u p p l e m e n t to all infants at r i s k o f BPD. During t h e transition p e r i o d , infants g e n e r a l l y r e c e i v e n u t r i t i o n both p a r e n t e r a l l y an d e n t e r a l l y . Th e recomm e n d e d amount o f v i t a m i n A to b e i n c l u d e d i n parenteral n u t r i t i o n i s 5 0 0 u g / k g p e r d a y . 6 3 No a d d i t i o n a l v i t a m i n - A s u p p l e m e n t s a re recommended. O n c e parenteral nutrit i o n is d i s c o n t i n u e d , and d u r i n g t h e s t a b l e - g r o w i n g p e r i o d , t he intake f r o m human m i l k is below t he e s t i m a t e d
qd uu art ie n. g6 3 t hOe n sc tea bpla er -e gn rt eo rw ai ln g n pu et rr ii ot di ,o n t hi se dv ii st ca omnitni-n Eu ec do ,n t ae nn dt o f a d e q u a t e volumes o f h u m a n m i l k s h o u l d meet t h e n e e d s o f most p r e t e r m i n f a n t s w i t h n o r m a l a b s o r p t i v e c a pacity. F o r infants fed f o r m u l a d e s i g n e d for p r e t e r m i n f a n t s , t h e n eed fo r a d d i t i o n a l v i t a m i n E d e p e n d s on t h e c o n c e n t r a t i o n s o f p o l y u n s a t u r a t e d f a t t y a c i d s and i r o n i n t h e f o r m u l a . A v i t a m i n - E i n t a k e f r o m f o r m u l a o f 4 mg p e r d a y o r m o r e , w i t h a r a t i o o f 1 . 0 mg o r m o r e o f v i t a m i n E t o l g o f l i n o l e i c an d l i n o l e n i c a c id s, r es ul ts i n n o r m a l plasma concentrations of vitamin E. During t h e p o s t d i s c h a r g e p e r i o d , no s u p p l e m e n t s are recommended for breast-fed infants. A m o n g t h o s e fed f o r m u l a , t h e n eed fo r a d d i t i o n a l v i t a m i n E depends on
intake needed to m a i n t a i n n o r m a l s e r u m concentrations.
t he c o n c e n t r a t i o n o f p o l y u n s a t u r a t e d fatty a c i d s and i r o n in the formula.
A t o t a l i n t a k e o f 4 5 0 j i g //kk g p e r d a y i s r e c o m m e n d e d f o r
i n f a n t s w i t h a b i r t h weight o f l e s s t h a n 1000 g b i r t h w e i g h t an d o f 200 t o 450 jig/ k g p e r d a y f o r t h o s e w i t h a b i r t h w e i g h t b e t w e e n 1000 an d 2000 g ( h i g h e r a m o u n t s p e r k i l o g r a m s h o u l d b e supplied to lo w e r - bir t h - w e ig h t infants and l o w e r amounts t o h e a v i e r i n f a n t s ) . F o r infants fed f o r m u l a for p r e t e r m i n f a n t s , t he need for additional v i t a m i n A d e p e n d s on t he c o n c e n t r a t i o n o f v i t a m i n A in t h e f o r m u l a and t h e volume o f f o r m u l a ingested. During t h e p o s t d i s c h a r g e p e r i o d , i t i s r e c o m m e n d e d t h a t i n fa n ts fed preterm-mother's milk receive a vitamin-A supplement u n t i l t h e y h a v e a c h i e v e d a w e i g h t o f 3.5 kg, w h e n be discontinued. Infants fed formula tf oh re ts eu rp mp l ie nmf ea nn tt s maat ya n a d e q u a t e v o l u m e ( 1 5 0 m t l i g p e r d a y or m o r e ) achieve the RNI. 5 Vitamin E
D i e t a r y v i t a m i n - E r e q u i r e m e n t s d e p e n d on t h e d i e t a r y c o n t e n t an d i n t e r a c t i o n o f vitamin E , p o l y u n s a t u r a t e d f a t t y a c i d s an d i r o n . V i t a m i n E i s f o u n d i n l ow c o n c e n t r a t i o n s in t h e p l a s m a and l i v e r o f infants b o r n p r e m a t u r e l y .' 3 At l e a s t 1 0 t r i a l s o f v i t a m i n E s u p p l e m e n t a t i o n have exami n e d it s effects on t h e r e t i n o p a t h y o f p r e m a t u r i t y ( R O P ) . A meta-analysis of the trials d o e s no t support supplem entation for the treatm ent o r prevention o f ROP.5' A l t h o u g h t h e r e i s n o c l e a r c l i n i c a l b e n e ift i ts eo ef mvsi t a m i n - E s ut po p lm ea mi en tn at ia nprudent tion in p r e m a t u r e i n f a n t s , p l a s m a v i t a m i n - E c o n c e n t r a t i o n s i n a r a n g e o f 10 t o 30 m g / L , a n d a r a t i o o f s e r u m c x - t o c o p h e r o l o f I mg or m o r e
Vitamin K
I n 1 9 8 8 t h e F e t u s an d N e w b o r n Commit t ee o f t h e Canadian P a e d i a t ri c S o ci et y ' r e c o m m e n d e d t h a t a l l p r e t e r m an d ill i n f a n t s r e c e i v e a 1 . 0 - m g i n t r a m u s c u l a r i n j e c t i o n o f v i ta m i n K , w i t h i n 6 h o u r s a f t e r b ir th t o p r e v e n t h e m o r r h a g i c d i s e a s e o f t he n e w b o r n . There is c o n f l i c t i n g evidence c o n c e r n i n g the efficacy of single or multiple oral d o s e s of vitamin K in c o m p a r i s o n w i t h intramuscular injection among t e r m infants; 5,116 the effect o f v i t a m i n - K s u p p l e m e n t a t i o n given orally among preterm infants ha s n o t been studied. In infants fed human m i l k e x c l u s i v e l y , serum c o n c e n t r a t i o n s o f p h y l l o q u i n o n e and i n t a k e o f vit a m i n K are v e r y l o w ; ' h o w e v e r , there is insufficient data to recommend suppl em en ta ti on in addition to the recommended prophylactic dose. Infants breast fed exclusively after discharge w h o are g i v e n antibiotics for a prol o n g e d p e r i o d o r w h o h a v e fat m a l a b s o r p t i o n may need
vitamin-K supplements. We c o n t i n u e to recommend that all p r e m a t u r e infants receive a 1.0-mg intramuscular dose of vitamin K within 6 h o u r s o f birth. F o r infants r e c e i v i n g parenteral nutrit i o n , 2 t o 100 j i g / k g p e r d a y o f v i t a m i n K s h o u l d b e p r o v i d e d until oral feeding is started.63 Water-soluble vitamins
T he r e i s little information a v a i l a b l e from w e l l -
CAN ME D ASSOC J * JUNE 1, 19 9 5 ; 152 (11)
1777
d e s i g n e d c l i n i c a l trials to s u p p o r t s p e c i f i c recommendat i o n s fo r i nt ake s o f most w a t e r - s o l u b l e v i t a m i n s . T h e r e f o r e , most o f t h e c u r r e n t recommendations a r e b a s e d on o b s e r v e d b i o c h e m i c a l responses to variations in enteral o r p a r e n t e r a l i n t ak e. , , - , To t h e b e s t o f c u r r e n t k n o w l edge, these estimates are safe. Further research is needed to d e t e r m i n e the optimal vitam in intakes. F o r inf ants f e d p a r e n t e r a l l y d u r i n g t h e t r a n s i t i o n and s t a b l e - g r o w i n g p e r i o d s , w e a g r e e w i t h t h e 1988 g u i d e -
b e c o n s i d e r e d o p t i ma l p r i m a r y nutritio n for p r e t e r m infants. In addition to the nutritional properties of human milk, breast-feeding ha s p s y c h o l o g i c benefits for the mother and anti-infective b e n e f i t s fo r t h e infant. I n f a n t s f e d t h e i r own m o t h e r ' s m i l k h a v e a l o w e r r i s k o f n e c r o t i z i n g e n t e r o c o l i t i s , 4 0 an d e v e n s h o r t - t e r m use o f preterm-mother's m i l k may b e associated w i t h long-term advantages for intellectual development.29 41 H o w e v e r , preterm -m other's m i l k is n o t c o m p l e t e l y ade-
on P e di a t ri c P a r e n te r a l N u t r i lines o f the e n t R e q u i r e Sm ue bn tc so m om fi tt th ee e A m e r i c a n S o c i e t y f o r C l i n i c a l N u t r i t i o n for t he u s e o f v i t a m i n s in t o t a l parenteral nutrition given to infants, including prem ature infants.63 Fo r infants fed e n t e r a l l y , t he P - R N I s for w a t e r - s ol u b l e vitam i n s , t h e v o l u m e s o f p r e t e r m - m o t h e r ' s m i l k and f o r m u l a r e q u i r e d to meet t h e s e P-RNI d u r i n g t h e s t a b l e - g r o w i n g p e r i o d and t h e r e c o m m e n d e d s u p p l e m e n t a l i n t a k e s a r e p r o v i d e d in Tab les 1 to 3.
q u a t e as a sole s o u r c e of nutrients, particularly protein, m i n e r a l s and some v i t a m i n s , o r t o d u p l i c a t e i n t r a u t e r i n e g r o w t h ( T a b l e 2 ) . 4 2 Th e u s e o f h u m a n - m i l k f o r t i f i e r s cont a i n i n g p r o t e i n , m i n e r a l s and v i t a m i n s e n s u r e s t h a t i n f a n t s fed their preterm-mother's m i l k receive a nutrient intake that meets e s t i m a t e d n e e d s . Powdered o r liquid f o r t i f i e r s may b e a d d e d to preterm -m other's m i l k that is expressed and f e d t o t h e i n f a n t b y t u b e o r b o t t l e . S i n c e l i q u i d hu m a n - m i l k fortifiers, u s e d in a 5 0 : 5 0 r a t i o w i t h human m i l k , contribute a s i g n i f i c a n t p r o p o r t i o n o f the infant s f l u i d inta ke , they are designed to contain adequate quantities of all e s s e n t i a l nutrients. H o w e v e r , m i x i n g preterm -m other's m i l k w i t h a n e q u a l volume o f liquid f o r t i f i e r dilutes t h e constituents of the human milk, including the nutrients, g r o w t h factors and anti-infective p r o p e r t i e s . 4 3 Powdered fortifiers allow the feeding of undiluted preterm-mother's milk. Lik e a n y p o w d e r e d - m i l k prod u ct, powdered fortifiers are n o t guaranteed microbiologically sterile, 4 although their u se is n o t associated w i t h i n c r e a s e d rates o f n e o n a t a l i n f e c t i o n . B e c a u s e p o w d e r e d f o r t if ie r is added to u n d i l u t e d milk, some n u t r i e n t s (particularly p r o t e i n and c a l c i u m ) ma y b e o v e r s u p p l i e d , d e p e n d i n g on t h e c o n t e n t o f t h e s e n u t r i e n t s in t h e mi l k . I n a d d i ti on , b e c a u s e a v a i l a b l e powd e r e d fortifiers may b e insoluble i n human milk, unless the f o r t i f i e r - m i l k m i x t u r e is well shaken, the nutrients may n o t b e available for absorption. There is limited e v i d e n c e to s u p p o r t nutrient forti fi ca-
F E E D I N G T H E I N F A N T B O R N PREMATURELY Th e C P S N u t r i t i o n Committee recommends f o r t i f i e d preterm-mother's milk or, alternatively, formula designed
for p r e t e r m infants as t he f e e d i n g o f c h o i c e for p r e m a t u r e i n f a n t s w i t h a b i r t h w e i g h t o f l e s s t h a n 1800 g an d p o s s i b l y u p t o 2 0 0 0 g o r a g e s t a t i o n a l a g e o f l e s s t h a n 34 w e e k s and p o s s i b l y up t o 3 8 weeks ( a t t h i s a g e t h e i n f a n t i s o f t e n a b l e t o n u r s e e f f e c t i v e l y ) . T h e b e n e fi fi t s o f f o r t i f i e d p r e t e r m - m o t h e r ' s m i l k and t h e need fo r a f o r m u l a fo r preterm infants become less apparent as the infant app r o a c h e s t h e w e i g h t and g e s t a t i o n a l a g e o f a t e r m i n f a n t , although a n exact we ig ht or gestational-age cut-off cann o t b e clearly defined. An e xc e p t i o n should b e made to t h e recommendation fo r l a r g e r p r e m a t u r e inf ants whose f l u i d intake is restricted o r w h o grow p o o r l y w h e n fed unfortified preterm-mother's milk. F o r infants w i t h a birth
wa be l ie g, h mt al ye s sb et hua sn e d 1 8w 0i 0t hg o, u tp r feo tr et ir f mi -c am to i to hn e ur nst i ml i lf ku l,l iff e ae vd a ii nl gha s been established d u r i n g the s t a b l e - g r o w i n g period, a t which point preterm-mother's m i l k s h o u l d b e f orti f i ed w i t h a n additional s o u r c e o f nutrients. If p r e t e r m- mo t h e r ' s m i l k is unavailable, f o r m u l a for p r e t e r m infants is r e c o m mended f r o m the beginning of enteral feeding.
for p r e t e r m infants ha s b e e n the subject of c o n t r o v e r s y and d e b a t e d u r i n g r e c e n t y e a r s . 3 9 E a r l y p r e t e r m - m o t h e r ' s m i l k ( fr o m the first p r o d u c t i o n o f c o l o s t r u m to 4 weeks
tn ui to rn i eo nf t sp r te htee re mv -i mdoetnhc ee r 'ss h om iwl sk . 5 3 6 9 , 4 H o w e v e r , f o r s o m e that a deficiency may deve lop if prem ature infants are fed preterm-mother's m i l k a l o n e an d t h a t their status i m p r o v e s i f t h e y a r e f e d f o r t i fied milk. The r e fo r e , f o r t i f i c a t i o n w i t h th ese nutrients total energy, protein, calcium, phosphorus, sodium, vitamins ( r i b o f l a v i n , v i t a m i n s A an d D) and i r o n ( d u r i n g t h e postdischarge period) s definitely indicated (Table 2). F o r zinc, f o l a t e , i o d i n e and m a g n e s i u m , t h e o r e t i c calculations s u p p o r t the n e e d for f orti f i cati on ; h o w e v e r , there is no e v i d e n c e o f nutrient deficiencies o r responses to fortification. Therefore, f o r t i f i c a t i o n w i t h these nutrients is o n l y provisionally recommended (Table 2). S u p p l e m e n t a t i o n may also b e i n d i c a ted if e l e m e n t s c o n t a i n e d i n a human-
am fo tte hr e br isr tdh e) l i i vs e rm eodr aet dt ee nr sm e a ni nd nt uh tu rs i ecnot ms e ts h ca ln o sme ir l k f r o m to providing the nutrient requirements of preterm infants. This observation supports the position that such milk should
milk fortifier reduce the b i oav ai l ab i l i ty of a n o t h e r nutrient ( e . g . , zinc, magnesium and ' m a n g a n e s e ) o r i n c r e a s e t h e r e q u i r e m e n t for a m e t a b o l i c c o f a c t o r (e.g., for v i t a m i n B 6 i n a protein supplement).
PRETERM-MOTHER'S MILK Th e us e o f human m i l k as a sole s o u r c e o f nutrients
1778
C AN M E D ASSOC J * l e r J U I N 1 9 9 5 ; 1 5 2
(11)
I n t a k e v o l u m e s o f formulas des ig ned f o r preterm i n f a n t s n e e d e d t o m e e t P-RNIs d u r i n g t he s t a b l e - g r o w i n g p e r i o d ( s e e Table 1 ) Table 3 :
F o r m u l a ; i n t a k e v ol u me n e e de d t o m e e t P-RNI, m L / k g p e r d a y except where i n d i c a t e d S i mi l a c S pe ci a l Care*t
Nutrient
EPF-Plus*t
SMA P r e e m i e * §
120-200
120-200
120-200
Energy
130-167
130-167
130-167
Protein
160-182
145-167
175-200
Carbohydrate
110-180
109-17 8
110-18 0
Calcium
122-182
122-182
214-3201F
Phosphorus
108-164
117-178
194-2951
Water Macronutrients
Minerals
81-16251
50-10091
Magnesium
70-140
Sodium
164-2631
180-287P
180-2871
Chloride
137-218i
129-206w
167-2681
122-17 0
130-18 2
Potassium
98-13711
Iron
750011
75001I
Zinc
42-671T
63-10091
63-1001T
Copper
34-60'1
73-125
100-1701T
Selenium
207-4141:
Chromium
NA
NA**
NA
NA
NA
8-759
4-3891
Manganese
7500'
4-38¶
NA
NA
NA
205-41011
500-10001i
360-7201
Vitamin D , m L / d
800
725
833
Vitamin A
4801
42711
6251'
Molybdenum
Iodine Vitamins
Vitamin E, m L / d
83-1 1 79
V i t a m i n C, mL/d
259
68-959
2591
167-2331T 10791
Vitamin B
20-259
20-259
50-6391
V itam in B,
72-929
72-921T
277-35411
Vitamin B .
25-3091
25-309
1 00-1209 1
3391
33T
Niacin
19-249
19-24T
Folate
16 7
Vitamin
B,,
mL/d
591
Biotin Pantothenic
acid
120-154
16 7
500Gb
5 09
839
160-20711
160-20711
751
665-8601
* E n e r g y concentration o f a l l formulas i s a s s u m e d t o b e 3 3 8 0 k J / L L tAbbott
Laboratories, Montreal.
PMe ad Johnson, Ottawa. § W y e t h - A y e r s t , North Y o r k , O n t . T h i s v o l u m e i s a b o v e t h e r e c o m m e n d e d f l u i d i n t a k e ( 1 2 0 t o 20 0 l i T h i s v o l u m e i s b e l o w t h e r e c o m m e n d e d f l u i d i n t a k e ( 1 2 0 t o 20 0 '-Not a v a i l a b l e .
mLikg
per d a y ) . m l/k g per day).
OC J C A N M E D A SSSS OC
* JUNE 1, 1 9 9 5 ; 152 (11)
1779
A l t h o u g h t he l o n g - t e r m effects o f f o r t i f i c a t i o n o f hu ma n m i l k h a v e y e t t o b e e v a l u a t e d , randomized t r i a l s h a v e shown th at infants g i v e n fortification h a v e faster rates o f growth t h a n t h o s e r e c e i v i n g unf ortif ied p r e t e r m mother's milk.6,69,47148 T h i s increas ed g r o w t h rate may l e a d t o s h o r t e r h o s p i t a l s t a y s , w i t h e conomic and p s y c h o l o g i c b e n e f i t s fo r t h e h o s p i t a l and t h e p a r e n t s . D u r i n g the transition period, w h e n g r o w t h is variable and inf ants a r e m e t a b o l i c a l l y unstab le, all i n f a n t s , r e g a r d -
similar to estimates of intrauterine growth, the c o m p o s i t i o n o f t h e n e w t i s s u e m a y n ot be i d e n t i c a l t o i n t r a u t e r i n e t i s s u e c o m p o s i t i o n . F o r m u l a s d o n ot c o n t a i n an y o f t h e b i o l o g i c a l l y a c t i v e i m m u n e s u b s t a n c e s , n or s o m e o f t h e e n z y m e s , hormones o r g r o w t h f a c t o r s , f o u n d in hu man m i l k . T h e l o n g - t e r m s i g n i f i c a n c e o f t h e l a c k o f t h e s e c o m p o n e n t s h a s n ot b e e n d e t e r m i n e d ; h o w e v e r , r e c e n t s t u d i e s s u g g e s t t h a t m e n t a l and motor d e v e l o p ment are affected by the t y p e of early fe e d ing pro-
less of birth weight, s h o u l d receive a c o m b i n a t i o n of p a r e n t e r a l an d e n t e r a l n u t r i t i o n . E x p r e s s e d p r e t e r m m o t h e r ' s milk , w i t h o u t f o r t i f i c a t i o n , is t h e first c h o i c e f or e nt er al f e e d i n g d u r i n g this p e r i o d . During t h e s t a b l e - g r o w i n g period, for all p r e t e r m infants regardless o f b ir t h w e i g h t , f e e d i n g e x c l u s i v e l y with p r e t e r m mother's m i l k d o e s n o t meet the P - R N I s . S u p p l e m e n t s o f energy, protein, calcium, phosphorus, sodium, vitamins A and D and r i b o f l a v i n a r e needed t o a c h i e v e t h e s e r e c ommended intakes (Table 2). Supplementation with vit a m i n B 6 , f o l a t e , z i n c , m a g n e s i u m an d i o d i n e a r e p r o v i s i o n a l l y i n d i c a t e d . I n a d d i t i o n , an i r o n s u p p l e m e n t i s r e c o m m e n d e d a f t er e r 2 m o n t h s . When a n i n f a n t i s a b l e t o n u r s e e f f e c t i v e l y ( a t a p o s t n a t a l a g e o f 34 t o 3 8 w e e k s an d a w e i g h t o f 1800 t o 2000 g ) , f o r t i f i c a t i o n m a y be stopped. There a re f e w d a t a on t h e g r o w t h and d e v e l o p m e n t of prem ature infants breast-fed m i l k exclusively during t h e p o s t d i s c h a r g e p e r i o d . I n f a n t s w i t h i l l n e s s e s and c o n d i t i o n s r e q u i r i n g c o m p l i c a t e d an d m e d i c a l c a r e a r e l i k e l y t o r e q u i r e more n u tri en ts . 3 T h i s g r o u p m a y b e n e f i t f r o m p r o l o n g e d f e e d i n g w i t h hum a n m i l k , accompanied by specific nutrient supplements. Until further data are a v a i l a b l e , h o w e v e r , e x c l u s i v e b r e a s t - f e e d i n g is recomm e n d e d u n t i l t he infant r e a c h e s 4 to 6 months c o r r e c t e d age, when solid f o o d s ho u ld b e introduced. Iron supplements s h o u l d be g i v e n beginning at 2 months and
v i d e d . 8 , 41
s( Th ao bu lle d 1 b) .e Gcro on wt ti hn u ae nd d t dh er vo eu lg oh po mu et n tt h me u sf itr s bt e y em ao rn i otf o rl ie f de c l o s e l y . A l t h o u g h t h e e f f e c t i v e n e s s an d t i m i n g o f b i o c h e m i c a l and h e m a t o l o g i c m o n i t o r i n g h a s n o t been e s t a b l i s h e d , blood tests s h o u l d be c a r r i e d o u t at 4 to 5 months c o r r e c t e d a g e to e n s u r e that t h e inf ant d o e s n o t ha v e a zinc deficiency, iron-deficiency a n e m i a o r early
P r e m a t u r e f o r m u l a s available in Canada h a v e e n e r g y c o n c e n t r a t i o n s o f 2796 o r 3380 k J / L , an d t h e n u t r i e n t c o m p o s i t i o n of e a c h fo r mu l a is s l i g h t l y d i f f e r e n t , r e f le c t i n g t he u n c e r t a i n t y a b o u t p r e m a t u r e infants' n e e d s for n u t r i e n t s , s p e c i f i c a l l y p r o t e i n - e n e r g y r a t i o , f a t b l e n d an d amounts o f c a l c i u m and p h o s p h o r u s . I n g e n e r a l , t h e f o r m u l a s p r o v i d e i n a d e q u a t e amounts o f s o d i u m , chloride, i o d i n e an d v i t a m i n s A an d D , an d e x c e s s i v e c o n c e n t r a t i o n s o f t r a c e m i n e r a l s and w a t e r - s o l u b l e v i t a m i n s ( T a b l e 3 ) . O t h e r t y p e s o f s p e c ia l i ze d i n f a n t f o r m u l a s , i n c l u d i n g soy-based, protein-hydrolysate, lactose-free, low-solute and h y p e r c a l o r i c f o r m u l a s , 5 were d e s i g n e d fo r t e r m inf ants and s h o u l d b e u s e d o n l y fo r l i m i t e d p e r i o d s , if at all, to feed premature infants. D u r i n g the transition period, if preterm-mother's milk is n o t available, f o r m u l a for p r e t e r m infants s h o u l d b e used; it may b e u s e d w i t h o u t s u p p l e m e n t a t i o n . M a n y clinicians a d v o c a t e a gradual increase in the c o n c e n t r a tion of e n e r g y in the formula to facilitate gastrointestinal tolerance; h o w e v e r , t h e be ne f it o f this practice is u n prov en. 52'53 During t h e stable-growing p e r i o d , if p r e t e r m- mo t he r 's m i l k is unavailable, f o r m u l a for p r e t e r m i n f a n t s is recommended. To meet t h e P - R N I s , t h e c o n c e n t r a t i o n o f e n e r g y in the f o r m u l a s h o u l d be 3 3 8 0 k J / L , an d s u p p l e m e n t s o f sodium an d c h l o r i d e , v i t a m i n s A an d D and i o d i n e may be n e e d e d . F o r m u l a fo r p r e t e r m i n -
c i r c u m s t a n c e s i n which f ee di ng a n i n f a n t p r e t e r m - m o t h e r ' s m i l k is i m p o s s i b l e , an d c o w ' s m i l k - b a s e d formulas for p r e t e r m infants s h o u l d b e used.
of fa n t1s8 0i s 0 u st uo a l2 l0y0 0g i gv, e nw hu in tci hl ci no fr arn et ss p ho an vd es at to t at ih ne e du s au awl e it gi hm et of discharge from the NICU.'54'56 Preliminary evidence shows th at p r e m a t u r e infants, e s p e c i a l l y t h o s e w i t h a b i r t h w e i g h t o f l e s s t h a n 1000 g , w h o h a v e i l l n e s s e s o r c o n d i t i o n s n e c e s s i t a t i n g c o m p l i c a t e d an d m e d i c a l c a r e may benefit f r o m p r o l o n g e d feeding w i t h formulas w i t h a higher nutrient concentration during the postdischarge period.3'.67 T h i s applies as well to infants w h o r e m a i n b e l o w t h e 3 r d p e r c e n t i l e f o r g r o w t h o r who h a v e i l l n e s s e s s u c h a s bronchopulmonary d y s p l a s i a . There have been f e w studies o f t he adequacy o f s t a n d a r d f o r m u l a d e s i g n e d fo r term i n f a n t s i n meeting v i t a m i n , m i n e r a l an d t r a c e - e l e m e n t n e e d s o f p r e m a t u r e infants, an d more re-
W p rho ev ind ef ea dn t io n ti na kf ea n ot sf ni un t ar di ee nq tusa tt eh a vt o pl ru mo em so ,t e tsh et sh ee fd ou rp ml ui lc aa -s t i o n o f i n tra u teri n e growth w i t h o u t undue m e t a b o l i c s t r e s s . 7 49 50 However, a l t h o u g h growth rates may be
se ev ai rd ce hn c ie n i ts h ai vs a ia lr aebal e i, s wr ee q u i r e d . H o w e v e r , u n t i l m o r e recommend the use of ironfortified f o r m u l a s d e s i g n e d for t e r m infants b e g i n n i n g at d i s c h a r g e until 1 2 months c o r r e c t e d age.
rickets.
FORMULA There a re m a n y
1780
CAN MED ASSOC J * le JUIN 1995; 152 (11)
1. N u t r i t i o n Committee, Canadian P aediatric S o c i e t y : F e e d i n g t h e l o w - b i rt h w ei g h t infant. C a n M ed As s oc J 1 9 8 1 ; 124: 1301-1311 2 . Lubchenco LO, H ans man C , D r e s s i e r M et al: Int r au t e r ine gr o wth a s e s t i m a t e d from l i v e - b o r n b i r t h wei gh t d a t a a t 24 t o 42 w e e k s o f g e s t a t i o n . P e d i a t r i c s 1 9 6 3 ; 32 : 793-800 3. American A c a d e m y o f P e d i a t r i c s Committee on N u t r i t i o n :
N u t r i t i o n a l needs for l o w - b i r t h - w e i g h t infants. P e d i a t r i c s 1985;
976-986
4 . C o m m i 7t5t: e e o n N u t r i t i o n o f t h e P r e t e r m I n f a n t , E u r o p e a n S o c i e t y o f P a ed i a tr i c G a s t r o e n t e r o l o g y an d N u t r i t i o n . N u t r i t i on an d f e e d i n g o f p r e t e r m infant s . A c t a P aediatr S c a n d S u p p i 1987; 3 3 6 : 1-14 5 . S h a f f e r S G , B r a d t S K , M e a d e SK e t a l : E x t r a c e l l u l a r f l u i d volume i n v e r y l ow b i r t h weight i n f a n t s d u r i n g t h e f i r s t 2 p o s t n a t a l m o n t h s . J Pe di a tr 1 9 8 7 ; 1 1 1 : 124-128 6 . B a u e r K , B o v e r m a n n G , R o i t h m a i e r A e t al: B o d y composit i o n , n u t r i t i o n , an d f l u i d b a l a n c e d u r i n g t he f i r s t t wo w ee ks o f l i f e i n p r e t e r m n e o n a t e s w e i g h i n g l e s s t h a n 1500 g r a m s . JPediatr 1 9 9 1 ; 1 1 8: 615-620 7 . L o r e n z J M , K l e i n m a n L I , K o t a g a l UR e t a l : W a t e r b a l a n c e i n v e r y l o w - b i r t h w e i g h t i n faf a n t s : r e l a t i o n t o w a t e r a n d sodium i n t a k e an d e f f e c t on o u t c o m e . J P e d i a t r 1 9 8 2 ; 1 0 1 : 423-432
d e t e r m i n a t i o n o f energy e x p e n d i t u r e , w a t e r i n t a k e , an d me t a b o l i z a b l e en ergy i n t a k e i n premature i n f a n t s . A m J C l i n N u t r 1 9 8 6 ; 4 4 : 315-322 sa n g R C , L u c a s A , U a u y R e t a l ( e d s ) : 1 9 . P u t e t G : E n e r g y . I n T sa N u t r i t i o n a l N eeds o f the Preterm In fan t: Scientific Basis a n d P r a c t i c a l G u i d e l i s i s , W i l l i a m s an d W i l k i n s , B a l ti m o r e , 1 9 9 3: 15-28 2 0. Z l o t k i n SH , B r y a n MH, Anderson G H : I n t r a v e n o u s n i t r o gen and energy i n t a k e s r e q u i r e d t o d u p l i c a t e in u t e r o nitrog e n a c c r e t i o n i n p r e m a t u r e l y born h u m a n i n f a n t s . J Pe di a t r 1 9 8 1 ; 9 9 : 115-120 2 1 . L e pa ge G , C o l l e t S , B o u g l e D e t al : T h e composition o f p r e t e r m m i l k i n r e l a t i o n t o t h e d e g r e e o f p r e ma t u ri t y . A m J C l i n N u t r 1 9 8 4 ; 4 0 : 1042-1049 2 2 . K u r z n e r S I , G a r g M , B a u t i s t a DB e t a l : G r o w t h f a i l u r e i n infants w i t h bronchopulmonary displasia: n u t r i t i o n and elev a t e d r e s t i n g metabolic e x p e n d i t u r e . P e d i a t r i c s 1 9 8 8 ; 8 1 : 379-384
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June 24-28, 1995: Canadian Paediatric Society A nnual M eeting Montreal Special lecturer: Dr. S usan King Study credits available. Danielle Solimka, C a n a d i a n Paediatric Socie t y , 4 01 S my th R d . , O t t a w a ON K 1 H 8 L 1 ; tel 6 1 3 7 38 - 39 0 0, fa x 6 1 3 7 3 7 - 2 7 9 4 June 26-27, 1995: S y m p o s i u m on Ge ne TherCurrent Status; Future a p y in Canada Prospects (cosponsored by the Canadian Institute for Biotechnology) Toronto Vicky F r a n c a v i l l a , administrative assistant, T o r o n t o B i o t e c h n o l o g y I n i t i a t i v e , PO B o x 4 46 , S t n . A , T o r o n t o O N M 5W 1 C 2 ; t e l 4 1 6 3 9 2 - 4 7 8 0 , fax 4 1 6 3 9 7 - 0 9 0 6 July 3-6, 1 9 9 5 : 1st International MultiDisciplinary C o n g r e s s o n Men -The D a w n i n g o f a Ne w M i l l e n n i u m : M e n R e s e a r c h , Knowledge and Action (in collaboration with the Faculty of Education, Continuing Profes-
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