Postnatal Malnutrition and Growth Retardation: An Inevitable Consequence of

Current Recommendations in Preterm Infants?

Nicolas E. Embleton, Naomi Pang and Richard J. Cooke
Pediatrics 2001;107;270-273
DOI: 10.1542/peds.107.2.270

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
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 Postnatal Malnutrition and Growth Retardation: An Inevitable
Consequence of Current Recommendations in Preterm Infants?
Nicolas E. Embleton, MB, BS, BSc, MRCPCH; Naomi Pang, BMedSci; and
Richard J. Cooke, MD, FRCPCH, FRCPI, FAAP
ABSTRACT. Background. Nutrient intakes meeting
recommended dietary intakes (RDIs) take time to estab-
lish and once established are rarely maintained through-
out hospital stay in preterm infants. A nutrient deficit,
therefore, accrues. RDI are based on needs for mainte-
nance and growth, with no provision to replace this def-
icit. We, therefore, hypothesized that postnatal malnutri-
tion and growth retardation were inevitable in infants
fed current RDI.
Methodology. Dietary intakes were prospectively col-
lected, by a single observer (N.P.), on a daily basis in a
group of preterm infants (n ⴝ 105; birth weight <1750 g;
gestational age <34 weeks) admitted to neonatal inten-
sive care unit over a 6-month period. Actual was sub-
tracted from recommended energy (120 kcal/kg/day)
and protein (3 g/kg/day) intakes and nutritional deficits
calculated. Infants were weighed on admission and
throughout hospital stay. The data were analyzed using a
combination of repeated measures analysis of variance
and stepwise regression analysis.
Results. Nutrient intakes meeting current RDIs were
rarely achieved during early life. By the end of the first
week, cumulative energy and protein deficits were 406 ⴞ
92 and 335 ⴞ 86 kcal/kg and 14 ⴞ 3 and 12 ⴞ 4 g/kg in
infants <30 and those at >31 weeks. By the end of the
fifth week, cumulative energy and protein deficits were
813 ⴞ 542 and 382 ⴞ 263 kcal/kg and 23 ⴞ 12 and 13 ⴞ 15
g/kg and the z scores were ⴚ1.14 ⴞ .6 and ⴚ.82 ⴞ .5 for
infants at <30 and >31 weeks. Stepwise regression anal-
ysis indicated that variation in dietary intake accounted
for 45% of the variation in changes in z score.
Conclusions. Preterm infants inevitably accumulate a
significant nutrient deficit in the first few weeks of life
that will not be replaced when current RDIs are fed. This
deficit can be directly related to subsequent postnatal
growth retardation. Pediatrics 2001;107:270 –273; postna-
tal growth retardation, preterm infants.
ABBREVIATIONS. RDI, recommended dietary intake; TPN, total
parenteral nutrition; SD, standard deviation; ANOVA, analysis of
variance.
From the Special Care Baby Unit, Royal Victoria Infirmary, Newcastle upon
Tyne, United Kingdom.
Received for publication Jan 3, 2000; accepted Jun 6, 2000.
Address correspondence to Richard J. Cooke, MD, FRCPCH, FRCPI, FAAP,
Ward 35, Leaze’s Wing, Royal Victoria Infirmary, Newcastle upon Tyne,
United Kingdom NE1 4LP. E-mail: r.j.cooke@ncl.ac.uk
PEDIATRICS (ISSN 0031 4005). Copyright © 2001 by the American Acad-
emy of Pediatrics.
270 PEDIATRICS Vol. 107 No. 2 February 2001
Downloaded from www.pediatrics.org by on July 26, 2009
A
dequate nutrition is critical to prevent early
postnatal growth retardation and to optimize
long-term growth and development in pre-
term infants. Current recommendations are to “pro-
vide nutrients to approximate the rate of growth and
composition of weight gain for a normal fetus of the
same post conceptional age.”1 However, nutrient in-
takes meeting recommended dietary intakes (RDIS)
take time to establish and once established are rarely
maintained throughout hospital stay.2– 4 We, there-
fore, hypothesized that postnatal malnutrition and
postnatal growth retardation were inevitable in pre-
term infants fed current RDI. Our purposes were to
prospectively document energy and protein intakes,
to compare these intakes with RDI, and to examine
the relationship between the accumulated deficit and
postnatal growth during initial hospital stay in pre-
term infants admitted to the neonatal intensive care
setting.
METHODS
This prospective study was conducted over a 6-month period
on all infants admitted to the neonatal intensive care unit at the
Royal Victoria Infirmary, Newcastle on Tyne. The local ethics
committee determined that written informed consent was not
necessary for the purpose of this audit.
Preterm infants with a gestational age of ⱕ34 weeks and a birth
weight ⱕ1750 g were considered eligible. Only those alive on day
2 of life were enrolled in the study. Gestational age was assessed
using maternal dates and fetal ultrasound. Body weight was mea-
sured using standard unit scales, accurate to 5 g.
All infants were fed according to a standard protocol that was
uniformly applied. The aims of this protocol are to establish an
energy intake ⱖ40 kcal/kg/day on day 1, commence total paren-
teral nutrition (TPN; 10% dextrose, 2.0 g protein/100 mL) on day
2, and commence intravenous lipids (2 kcal/mL) and enteral feeds
on day 3. Enteral feeds, with human milk or a term infant formula
(20 cal/oz, 2.0 g protein/100 kcal) are begun at .5 to 1.0 mL/kg/
hour and increased at a rate of 20 mL/kg/day. When an enteral
intake of 150 mL/kg/day is established infants fed human milk
are transitioned to 50% human milk and 50% standard preterm
formula (24 kcal/oz, 2.7 g protein/100 kcal) over a 2-day period,
fed in alternate syringes. Infants not fed human milk were tran-
sitioned to 100% preterm formula over a 4-day period. Infants are
fed by continuous infusion until ⬃32 to 33 weeks’ corrected age, at
which point bolus feeds are introduced.
The unit approach to supplementation of human milk is, per-
haps, unusual. Seventy to 80% of our mothers choose to provide
breast milk. However, the volume of milk varies and infants may
be fed varying amounts of mother’s milk ⫹ human milk fortifier
and/or preterm formula. Because infants fed preterm formula
grow better than those fed fortified human milk4,5 and because it
is easier to implement in a consistent manner we choose to sup-
plement human milk with preterm formula.
Intake data, actual not prescribed, were collected on a daily
basis by a single observer (N.P.). Human milk was assumed to
contain 75 kcal/100 mL and 1.4 g of protein/100 mL.6,7 Formula
intakes were based on published manufacturer’s figures. An en-
ergy intake of 120 kcal/kg/day was assumed to be adequate.1
Recommended protein intakes vary from 3.0 to 3.8 g/kg/day8 and
an intake of 3.0 g/kg/day was considered acceptable.
Actual intake was subtracted from RDI to calculate daily defi-
cit, which was then summed to calculate cumulative deficit.
Weight was converted to standard deviation (SD; z) scores using
the British reference standards.9 Changes in z score were calcu-
lated by subtracting current z score, corrected for postconceptual
age, from that at birth.
Infants were stratified by gestational age (ⱕ30 and ⱖ31 weeks’
gestation. The data are presented as mean (⫾ SD) unless otherwise
stated and were analyzed using repeated measures analysis of
variance (ANOVA), with gestational age as a blocking variable.
Stepwise regression analysis was used to examine the relationship
between birth weight, gestational age, postnatal age, energy def-
icit, and protein deficit and changes in z score. Results were
considered significant at P ⬍ .05.

RESULTS
One hundred five infants were studied with a
mean (⫾ SD) birth weight of 1285 ⫾ 322 g and a
gestational age of 30 ⫾ 2.3 weeks. Infants were fol-
lowed until death (n ⫽ 11), transfer to referral hos-
pital (n ⫽ 57), or discharge home (n ⫽ 37). None of
the surviving infants developed necrotizing entero-
colitis, a patent ductus arteriosus, or required steroid
therapy.
TPN was commenced at 3 ⫾ 1 days of age. Enteral
feeds were begun at 3 ⫾ 1 days; by 4 days, 84% of
infants had received enteral feeds. Full enteral feeds
were established at 10 ⫾ 6 days; by 12 days, 80% of
infants were tolerating an enteral intake of ⱖ150
mL/kg/day.
Daily energy intake and daily cumulative deficits
during the first week of life are presented in Fig 1.
Although intakes increased rapidly (P ⬍ .0001), in-
fants ⱕ30 had lower daily energy (60 ⫾ 25 ⬍ 72 ⫾ 30
kcal/kg/day; P ⬍ .001) and protein intakes (1.0 ⫾
1.0 ⬍ 1.4 ⫾ 1.0 g/kg/day; P ⬍ .001) than those at ⱖ31
weeks’ gestation. By the end of the first week, cumu- Fig 1. Nutrient intake and cumulative nutrient deficit during the
lative energy and protein deficits were 406 ⫾ 92 and first weeks of life. Data were analyzed using ANOVA. The asterisk
335 ⫾ 86 kcal/kg and 14 ⫾ 3 and 12 ⫾ 4 g/kg in indicates the overall level of significant difference between infants
at ⱕ30 weeks and ⱖ31 weeks as determined using ANOVA.
infants ⱕ30 and those at ⱖ31 weeks, respectively.
Weekly nutrient intakes and cumulative deficits
are presented in Fig 2. Intakes and deficits increased DISCUSSION
between weeks 1 and 2 (ⱖ31 weeks; P ⬍ .001) and This was a observational study designed to deter-
between weeks 1 and 5 (ⱕ30 weeks; P ⬍ .001) but mine what really happens in this unit and the results
stabilized thereafter. Overall, intakes were less and are influenced by our approach to nutritional care.
deficits were greater in infants ⱕ30, compared with Thus, more aggressive TPN with higher energy and
those at ⱖ31 weeks’ gestation (P ⬍ .0001). By the end protein intakes might have reduced the energy and
of the fifth week, cumulative energy and protein protein deficit. However, early TPN is limited by
deficits were 813 ⫾ 542 and 382 ⫾ 263 kcal/kg and glucose and lipid intolerance and concerns regarding
23 ⫾ 12 and 13 ⫾ 15 g/kg for those at ⱕ30 and ⱖ31 amino acid metabolism. Constant energy and protein
weeks, respectively. intakes of ⱖ80 kcal and ⱖ2.0 g/kg/day are rarely
The mean changes in z scores between birth and 7 established in the smaller sicker infants during early
weeks are also presented in Fig 2. Mean changes in z life, irrespective of the regimen used.2– 4
score fell from 0 at birth to ⫺1.04 ⫾ .8 at 7 weeks (P ⬍ More aggressive enteral feeding might also have
.0001). Between birth and 14 days, scores were sim- reduced the deficit. Nevertheless, enteral feeds were
ilar in infants ⱕ30 and ⱖ31 weeks’ gestation. After 2 introduced early and full enteral feeds were estab-
weeks, z score stabilized in infants ⱖ31 weeks but lished in 80% of infants by day 12. No infants devel-
continued to decrease until 5 weeks in infants at ⱕ30 oped necrotizing enterocolitis during the study but
weeks’ gestation. Stepwise regression analysis indi- whether earlier introduction and more rapid ad-
cated that ⬃52% of the variation in z scores could be vancement in enteral volumes is achievable without
explained by the cumulative energy deficit (⬃45%) adverse effects is not clear.
and gestational age (⬃7%), cumulative protein defi- What is clear is that early nutritional deficits were
cit had no significant effect. not regained before hospital discharge. This is not

ARTICLES 271
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Fig 2. Nutrient intake, cumulative nutrient deficit, and changes
in Z score during hospital stay. The asterisk indicates the overall
level of significant difference between infants at ⱕ30 weeks and
ⱖ31 weeks as determined using ANOVA. Numbers in enclosed
brackets indicate sample size at that time point.
surprising. Infants were fed nutrient intakes de-
signed to meet current RDI. Current RDIs are based
on needs for maintenance and normal growth and no
provision is made for catch-up growth. The situation
is further compounded during subsequent weeks
when feeds were interrupted for clinical reasons but
a delay ensued before full feeds were reestablished.
There is no good evidence to suggest that needs for
272 POSTNATAL MALNUTRITION AND GROWTH RETARDATION FOR PRETERM INFANTS
Downloaded from www.pediatrics.org by on July 26, 2009
catch-up are different from those of normal growth.
It has, therefore, been suggested that needs for
catch-up be added to those of normal growth and
replaced before hospital discharge.10 Depending on
the size of the deficit, this may or may not be possible
but such an approach is not widely practiced and
merits consideration.
In this study, energy deficit (374 kcal/kg) peaked
by 14 days in infants ⱖ31 weeks’ gestation. Assum-
ing that intake was maintained between 14 days and
36 days of age, the mean age at hospital discharge, a
further 18 kcal/kg/day would be needed for catch-
up. Infants at ⱕ30 weeks had an energy deficit of 590
kcal at 14 days. However, this continued to increase
to 813 kcal/kg at 35 days and it is unlikely that the
deficit (39 kcal/kg/day) could have been replaced
before hospital discharge at 56 days of age.
The relationship between nutrient intake and
growth is intriguing. Carlson and Ziegler4 examining
growth in preterm infants noted that poorer gain was
more marked in infants fed fortified human milk
than preterm formula. Because energy intakes were
similar but protein intakes were less, it was sug-
gested that poorer growth reflected inadequate pro-
tein intake.4 In this study poorer growth was primar-
ily related to inadequate energy intake. Comparisons
between these 2 studies are difficult but might be
interpreted to make a point.
Nutritional requirements and intake vary depend-
ing on patient population; the smaller the infant, the
more complicated the perinatal course, the greater
the variation in requirements and intake. Feeding
practices also vary11,12 further increasing variation in
intake. Thus, the nature and amount of the nutri-
tional deficit will differ between infants and nurser-
ies and what is rate-limiting in one situation may not
be rate-limiting in another.
It is generally assumed that poor growth in pre-
term infants primarily reflects inadequate nutrient
intake. In this study, ⬃45% of the variation in growth
was related to intake, with an additional 7% of the
variation in growth relating to birth weight. Thus,
45% of the variation in growth was not explained
demonstrating the heterogeneous nature of this
group of infants. Nonetheless, it does underline the
importance of controlling for nonnutritional factors
when examining the effects of dietary intervention.
The results of this simple study are important. On
a day-to-day basis, quality of nutritional care is as-
sessed by examining daily nutrient intake. Data from
this study suggest a more realistic picture can be
obtained by expressing the data as cumulative nutri-
ent deficit. Whether deficits can be recouped during
initial hospital stay is not clear. What is clear is that
they will never be recouped if infants are fed intakes
meeting current RDI. A randomized, controlled trial
will be needed to more closely examine this issue.
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Postnatal Malnutrition and Growth Retardation: An Inevitable Consequence of
Current Recommendations in Preterm Infants?
Nicolas E. Embleton, Naomi Pang and Richard J. Cooke
Pediatrics 2001;107;270-273
DOI: 10.1542/peds.107.2.270
Updated Information including high-resolution figures, can be found at:
& Services http://www.pediatrics.org/cgi/content/full/107/2/270
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