Preterm Birth and Body Composition at Term Equivalent
Age: A Systematic Review and Meta-analysis
abstract
BACKGROUND AND OBJECTIVE: Infants born preterm are significantly
lighter and shorter on reaching term equivalent age (TEA) than are
those born at term, but the relation with body composition is less
clear. We conducted a systematic review to assess the body composition at TEA of infants born preterm.
METHODS: The databases MEDLINE, Embase, CINAHL, HMIC, “Web of
Science,” and “CSA Conference Papers Index” were searched between
1947 and June 2011, with selective citation and reference searching.
Included studies had to have directly compared measures of body
composition at TEA in preterm infants and infants born full-term. Data
on body composition, anthropometry, and birth details were extracted
from each article.
RESULTS: Eight studies (733 infants) fulfilled the inclusion criteria.
Mean gestational age and weight at birth were 30.0 weeks and 1.18
kg in the preterm group and 39.6 weeks and 3.41 kg in the term group,
respectively. Meta-analysis showed that the preterm infants had
a greater percentage total body fat at TEA than those born full-term
(mean difference, 3%; P = .03), less fat mass (mean difference, 50
g; P = .03), and much less fat-free mass (mean difference, 460 g; P ,
.0001).
CONCLUSIONS: The body composition at TEA of infants born preterm is
different than that of infants born at term. Preterm infants have less
lean tissue but more similar fat mass. There is a need to determine
whether improved nutritional management can enhance lean tissue
acquisition, which indicates a need for measures of body composition
in addition to routine anthropometry. Pediatrics 2012;130:e640–e649
AUTHORS: Mark J. Johnson, BSc, BM, MRCPCH,a,b Stephen
A. Wootton, BSc, PhD,a,c Alison A. Leaf, MB, ChB, MD,
FRCPCH,a,b and Alan A. Jackson, MB, BChir, MD, FRCP,
FRCPCH, FRCPatha,c
aSouthampton NIHR Nutrition, Diet and Lifestyle Biomedical
Research Unit, and bDepartment of Neonatal Medicine, Princess
Anne Hospital, University Hospital Southampton NHS Foundation
Trust, Southampton, United Kingdom; and cInstitute of Human
Nutrition, University of Southampton, Southampton, United
Kingdom
KEY WORDS
infant, premature, body composition, adiposity, leanness,
nutrition assessment, nutrition requirements, infant nutrition,
growth
ABBREVIATIONS
ADP—air-displacement plethysmography
ATV—adipose tissue volume
CI—confidence interval
DXA—dual energy x-ray absorptiometry
FFM—fat-free mass
FM—fat mass
SD—Standard Deviation
%TBF—total body fat as a percentage of body weight
TBW—total body water
TEA—term equivalent age
Dr Johnson made a substantial contribution to conception and
design of the study, the acquisition of data, the analysis and
interpretation of data, drafting of the article, and revising it
critically for important intellectual content; Dr Wootton made
a substantial contribution to the conception and design of the
study, the analysis and interpretation of data, and revising the
article critically for important intellectual content; Dr Leaf made
a substantial contribution to the analysis and interpretation of
data, drafting of the article, and revising the article critically for
important intellectual content; Professor Jackson made
a substantial contribution to the analysis and interpretation of
data and revising the article critically for important intellectual
content; and all authors gave final approval of the version of the
article to be published.
www.pediatrics.org/cgi/doi/10.1542/peds.2011-3379
doi:10.1542/peds.2011-3379
Accepted for publication May 1, 2012
(Continued on last page)
e640
JOHNSON et al
REVIEW ARTICLE
A goal for the nutritional care of infants
born preterm is to achieve rates of
growth similar to those of the fetus in
utero at the equivalent gestation.1 This
growth needs to be similar both qualitatively and quantitatively, so that both
the size and body composition of the
preterm infant at term equivalent age
(TEA) are similar to those of infants
born at full-term. In practice, intrauterine growth rates are a difficult target
to achieve and “extrauterine growth
restriction” is common.2 However, while
there is good evidence that preterm
infants do not currently achieve the size
of term infants at TEA,3 it is less clear
whether the pattern of tissue growth is
similar to that of infants born at term. It
is recognized that body size and composition in early life relate to the risk of
noncommunicable diseases, such as
coronary heart disease, in later life;
therefore, understanding the body composition at TEA of preterm infants is important.4–6 The composition of weight
gain in low birth weight infants varies in
response to nutrient intake,7 and an
objective for improved nutritional management could be the acquisition of an
appropriate body composition in preterm infants by TEA.
Studies exploring the relationship between preterm birth and body composition at TEA have had mixed findings. In
part, this may be explained by the use
of a variety of methods for measuring
neonatal body composition by different
investigators, including isotope dilution, dual energy x-ray absorptiometry
(DXA), air-displacement plethysmography (ADP), and MRI. All of these methods
are indirect and rely on a range of
assumptions, not all of which have been
appropriately validated for this population.8,9 No single method has been
shown to give a more reliable estimate
of body composition than another.
Care has to be taken to recognize
that for preterm infants, intrauterine
growth itself may have been constrained.
PEDIATRICS Volume 130, Number 3, September 2012
Infants born preterm may experience
different patterns of growth in utero
before delivery compared with infants
born at term.10 Thus, any comparison
between full-term infants with those
born preterm at TEA may be comparing
groups that were different at the
equivalent intrauterine age. Hence, the
assumption that a comparison is being
made between ex utero tissue accretion (in the preterm infants) with in
utero tissue accretion (in the full-term
group) may not be justified.
There is a need to better define the
relationship between preterm birth
and body composition at TEA. We
therefore set out to systematically review the available literature and conduct a meta-analysis to determine if
differences in body composition could
be identified between infants born
preterm upon reaching TEA and those
born at term with regard to fat-free
mass (FFM), fat mass (FM), and total
body fat as a percentage of body weight
(%TBF).
METHODS
Search terms, inclusion criteria, and
methods of analysis were documented
in a protocol in advance of the start of
the review; the details follow.
Eligibility Criteria
Types of Studies
All types of studies were considered for
review and no language restrictions
were imposed.
Types of Participants
Only studies that made direct comparisons between premature infants
(born at ,37 weeks’ gestation) at TEA
(37–42 weeks’ postmenstrual age) and
infants born at term using the same
method were selected for review. Studies where the preterm population was
assessed at ,37 weeks’ postmenstrual
age were excluded.
Studies assessing the effects of modified feeds were excluded, as were
studies looking specifically at infants
born small or large for gestational age,
infants of diabetic mothers, or infants
with specific conditions (eg, chronic
lung disease, congenital heart disease).
Types of Methods
To be included, studies had to have
measured a defined component of body
composition (FFM, FM, or %TBF) by using
a recognized technique for measuring
neonatal body composition.8,9 Studies in
which estimates of body composition
were based on a derivation with formulas using anthropometry, skin folds,
or bioelectrical impedance (“doubly indirect” methods) were excluded.
Types of Outcome Measures
The primary outcome measures for the
study were the differences in components of body composition (FM, FFM,
and %TBF) in preterm infants at TEA
compared with those born full-term.
Secondary outcome measures were
differences in weight, length, and head
circumference in preterm infants at TEA
compared with those born full-term.
Searches and Information Sources
An all language literature search was
carried out using the key words and
search strategy detailed in Table 1. The
electronic databases MEDLINE (1947 to
present), Embase (1947 to present),
CINAHL (1981 to present), and Health
Management Information Consortium
were searched by using OvidSP (Wolters
Kluwer, www.ovid.com). The last search
was run on June 1, 2011.
Conference abstracts and other citations were identified by searching the
web sites “Web of Science” (wok.mimas.
ac.uk) and CSA Conference Papers Index
(www.csa.com) using the same search
strategy outlined in Table 1, adapted for
use in the web interface. Handsearching
of conference proceedings was also
e641
TABLE 1 Search Terms and Corresponding
Numbers, With Strategy Used for
Electronic Searches
Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Search Term
exp Body Composition/
(body adj composition).mp.
fat*.mp.
thin*.mp.
adipos*.mp.
(bone adj mineral).mp.
(total adj body).mp.
exp Infant, Newborn/ or
neonate*.mp. or newborn*.mp.
water*.mp.
(fat adj mass).mp.
(body adj fat).mp.
adiposity.mp.
(fat adj free).mp.
lean.mp
exp Infant, Premature/ or
preterm*.mp.
prematur*.mp.
15 or 16
9 or 10 or 11 or 12 or 13 or 14
1 or 2 or 3 or 4 or 5 or 6 or 7
8 and 17 and 18 and 19
Searches were performed by using OvidSp, where “.mp.”
represents a multipurpose search across the fields of title,
abstract, subject headings, heading word, drug trade
name, original title, device manufacturer, and drug manufacturer.
carried out. Citation and reference
searching was performed on articles
selected for review.
Study Selection
Articles were selected for review on the
basis of titles and abstracts where
possible, and by using the article where
necessary or in the presence of any
doubt. The full text of any potentially
eligible report was then reassessed
against the selection criteria and included or excluded as appropriate. This
process was carried out by a single
author (M.J.).
circumference at the time of study. With
numerical data, both mean and standard
deviation (SD) values were extracted. For
included studies where data for FM, FFM,
and %TBF were not published in the
original article, authors were contacted
and asked if they could provide this
information. While 5 responded, only 1
author was able to provide additional
information (E. Olhager, personal communication, September 29, 2010).
Assessment of Heterogeneity and
Risk of Bias for the Included
Studies
Given the variety of different methods
used to assess body composition in
infants, the main factors likely to cause
bias and imprecision for the included
studies were the precision and validity
of the methods used. The cited references regarding the method and validation work used in each study were
therefore examined to help inform the
assessment of bias and precision. In
addition, the postnatal age in days of the
full-term infants at the time of study was
anticipated to cause a degree of bias in
assessing body composition due to the
rapid changes in total body water (TBW)
over the first 2 weeks after birth.11,12
It was anticipated that, due to the variation in methodology between studies,
there would be considerable heterogeneity. The decision was taken to only
include studies that directly compared
both full-term and preterm infants at
TEA using the same method to allow for
this.
Data Synthesis and Analysis
Data Collection
Dataextractionwascarriedoutbyasingle
author (M.J.) using a specially designed
spreadsheet, which collected data on the
methods, study aims, study design, gestational age at birth, birth weight, body
composition at TEA (in terms of FM, FFM,
and %TBF), chronological age, postmenstrual age, weight, length, and head
e642
JOHNSON et al
Meta-analysis was performed looking
at the difference in means between
preterm infants at TEA and infants born
full-term using the random-effects model. Mean differences with 95% confidence intervals (CIs) were calculated for
each outcome measure. Analysis was
carried out by using the software Review
Manager v5.1.13
Heterogeneity across studies for each
outcome measure was assessed according to the method of Higgins et al,
using the I2 measure to describe the
percentage of the variability in effect
due to heterogeneity.14 In cases where
SDs were not given, these were calculated from CIs if available or from the
median and the range as described by
Hozo et al.15
While DXA and ADP provide data on the
fat component of body composition as
FM, MRI techniques give adipose tissue
volume (ATV). Therefore, for MRI studies
where ATV was provided rather than FM,
ATV was converted to FM by using
a conversion factor of 0.66 kg of FM for
every 1 L of ATV.16
RESULTS
Study Selection
A flowchart of the review process is
shown in Fig 1. Initial searches identified 954 articles and abstracts for review. After removal of duplicates, there
were 658 articles that were screened
for eligibility; 616 were discarded as it
was clear from their abstracts or titles
that they did not meet the criteria.
Common reasons for rejection included
the assessment of body composition
in preterm infants only without term
controls, the use of doubly indirect
methods for assessing body composition, focus on a specific disease
population, the comparison of novel
feeds, and reviews concerning nutritional management. The remaining 42
citations were selected for full-text
review, of which 34 were excluded
for the reasons given in Fig 1. Eight
studies met the inclusion criteria
and were included in the systematic
review.
Study Characteristics
The 8 included studies, together with
their characteristics, participants, and
methods, are shown in Table 2.
REVIEW ARTICLE
age. There was thus no significant difference in the postmenstrual age at
assessment between the 2 groups (P =
.10). For Ahmad et al,17 only the term
and preterm 23- to 28-week groups
were included in the meta-analysis, as
the other subgroups (29- to 32-week and
33- to 36-week gestations) had not been
assessed at TEA (mean ages at assessment, 35.3 and 35.6 weeks, respectively).
Forest plots for the meta-analyses of
body composition and anthropometry
are shown in Figs 2 and 3, respectively,
and the results are summarized in Table 3
and discussed later. Results shown are
given as mean (95% CI, P value).
Risk of Study Bias
FIGURE 1
Flow chart of review process.
The included studies had a total study
population of 733 and were undertaken
in neonatal units in Europe, Australia,
and North America. The preterm group
at TEA totaled 388, with a mean gestational age at birth of 30.0 (SD 2.6) weeks
and a mean birth weight of 1.18 (SD
0.33) kg. The full-term group totaled 345,
with a mean gestational age at birth of
39.6 (SD 1.3) weeks and a mean birth
weight of 3.41 (SD 0.60) kg.
Body composition in the preterm group
was assessed at a mean of 39.5 (SD 1.5)
weeks’ postmenstrual age, and the fullterm group was assessed at a mean of
39.8 (SD 1.4) weeks’ postmenstrual
Investigation into the relative accuracy
and validity of the 3 methods (DXA, ADP,
and MRI) used across the included
studies revealed that while they all had
similar precision (represented by coefficients of variation ranging from 3% to
8% in published validation studies),26–34
they differed in their ability to accurately estimate FM and %TBF in relation
to the reference standards or techniques used in their validation. Validation
work referenced by the studies included
in the review that used DXA showed that
it tended to overestimate FM or %TBF by
12% to 30%,26 while in the methodologic
references for studies using ADP, this
figure was lower, with ADP differing
from the reference standard by 0.05%
TABLE 2 Characteristics of Included Studies
Study
al17
Ahmad et
(2010)
Roggero et al18 (2009)
Olhager (personal communication,
2010) and Olhager and
Forsum19,20 (2003, 2006)
Uthaya et al21 (2005)
Atkinson et al22 (1994)
McLeod et al23 (2009)
Vasu et al24 (2009)
Fusch et al25 (1999)
Method Used
Sample Size, n
Mean GA at
Birth, wk
Mean birth
weight, kg
Mean GA at
Assessment, wk
Body Composition
Data Available
Preterm
Full-term
Preterm
Full-term
Preterm
Full-term
Preterm
Full-term
DXA
ADP
MRI
20
159
8
39
87
9
25.9
29.9
33.0
39.4
38.6
40.7
0.865
1.118
1.820
3.519
3.192
3.895
38.6
39.5
40.6
40.1
39.0
41.9
%TBF, FFM, FM
%TBF
%TBF, FFM, FM
MRI
DXA
ADP
MRI
DXA
38
69
20
22
52
29
87
14
39
41
28.8
30.2
30.6
28.9
32.0.
39.9
40.0
39.0
40.2
40.0
1.190
1.000
1.140
1.300
1.570
3.470
3.500
3.200
3.400
3.530
38.6
39.5
39.5
39.5
40.0
40.2
40.2
39.5
39.5
40.0
%TBF, FM
%TBF
%TBF
FFM, FM
%TBF, FM
GA, gestational age.
PEDIATRICS Volume 130, Number 3, September 2012
e643
FIGURE 2
Forest plots of meta-analyses of differences in (A) %TBF, (B) FM, and (C) FFM between infants born preterm at TEA and those born full-term.
to 0.6% in either direction.29–31 Studies
referenced for method validation work
in neonatal MRI suggested it tended to
overestimate %TBF by ∼6%.33,34
The decision to look at the differences
between body composition in the study
populations rather than the absolute
values should, in theory, allow them to
be considered and analyzed together.
e644
JOHNSON et al
However, in view of this variation in
method accuracy, an overall metaanalysis for each outcome was performed, and subgroup analysis of studies
using the same methods was carried out
to aid interpretation of results.
Specific data regarding the chronological age of the full-term infants at the
time of study was only available in 3 of
the 8 studies. However, with the exception of one study,20 in which the full-term
infants were studied at a mean age of
16 days, the full-term infants were
studied within the first week of life. TBW
is relatively high at birth and then falls
rapidly over the first week of life,
meaning that the full-term infants are
likely to have had relatively higher TBW
REVIEW ARTICLE
FIGURE 3
Forest plots of meta-analyses of differences in (A) weight, (B) length, and (C) head circumference between infants born preterm at TEA and those born full-term.
compared with the preterm infants,
who were measured when much older
(∼2 months of age).12,35 This potentially
could have influenced measures of FFM
in the full-term group, although it is
likely that any effect would have been
minimal, as the change in TBW as
a proportion of body weight over the
first days of life is in the order of 2%.36
Primary Outcomes: Body
Composition
Percentage Total Body Fat at TEA in
Preterm Versus Full-term Infants
Seven of the 8 studies assessed %TBF
(n = 672; 366 preterm and 306 full-term
infants). Meta-analysis of all 7 showed that
infants born preterm had significantly
greater %TBF at TEA by 3.06% (95% CI
0.25%–5.88%, P = .03; see Forest plot in
Fig 2A) compared with infants born at
full-term, with significant heterogeneity (I2 = 93%, P , .001). For the methodology subgroups, the heterogeneity
was less and it was only in the ADP
subgroup that preterm infants at TEA
had significantly greater %TBF compared with infants born full-term.
TABLE 3 Summary of Results of Meta-analyses
Outcome
No. of Studies Included in the
Meta-analysis (No. of Patients)
Mean Effect of Preterm Birth on
Body Composition at TEA Compared
With Infants Born Full-term (95% CI)
P
%TBF
7 (672)
.03
FM
5 (297)
FFM
3 (137)
Weight
7 (577)
Length
4 (383)
Head circumference
5 (450)
Increased in preterm infants by
3.0% (0.25%–5.88%)
Decreased in preterm infants by
50 g (10–90 g)
Decreased in preterm infants by
460 g (270–340 g)
Decreased in preterm infants by
590 g (440–750 g)
Decreased in preterm infants by
3.7 cm (2.8–4.6 cm)
Decreased in preterm infants by
1 cm (0.5–1.5 cm)
PEDIATRICS Volume 130, Number 3, September 2012
.02
,.0001
,.0001
,.0001
,.0001
Fat Mass at TEA in Preterm Versus
Full-term Infants
Five of the included studies contained
data for FM (n = 297, 140 preterm infants and 157 full-term infants). Metaanalysis of these 5 studies showed that
preterm infants had significantly less
FM at TEA compared with those born
full-term. The mean difference was 50 g
(95% CI 10–90 g, P = .02; see Forest plot
in Fig 2B). There was no evidence of
heterogeneity (I2 = 0%). For the
e645
methodology sub-groups, neither the
DXA nor MRI subgroups showed a
significant difference in FM between
preterm at TEA and full-term born
infants.
Fat-Free Mass at TEA in Preterm
Versus Full-term Infants
In the 3 studies that reported data on
FFM (n = 137, 50 preterm and 87 fullterm infants), meta-analysis showed
that preterm infants at TEA had significantly less FFM than full-term infants,
with a mean difference of 460 g (95% CI
0.27–0.64, P , .001; see Forest plot
in Fig 2C). As for FM, the heterogeneity
(I2 = 57%) was not significant (P = .10).
The findings were consistent for the
methodology subgroups, with both MRI
and DXA showing significantly less FFM
in the preterm infants at TEA.
Secondary Outcomes:
Anthropometry
Weight at TEA in Preterm Versus
Full-term Infants
Seven studies reported data for weight
at TEA (n = 577, with 319 preterm and
258 full-term infants). Meta-analysis
showed that preterm infants at TEA
age were significantly lighter than fullterm infants by a mean of 590 g (95% CI
440–750 g, P , .001; see Forest plot in
Fig 3A).
Length at TEA in Preterm Versus
Full-term Infants
Meta-analysis of the 4 studies that had
comparative figures for length (n = 383,
with 209 preterm and 174 full-term)
showed that preterm infants at TEA
were significantly shorter by a mean of
3.71 cm (95% CI 2.81–4.60 cm, P , .001;
see Forest plot in Fig 3B).
Head Circumference at TEA in Preterm
Versus Full-term Infants
Head circumference was assessed in
both groups at TEA in 5 studies (n = 450,
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JOHNSON et al
with 247 preterm and 203 full-term).
Meta-analysis showed that head
circumference at TEA was significantly less in the preterm group by
a mean of 1.03 cm compared with
infants born full-term (95% CI 0.54–
1.52 cm, P , .001; see Forest plot in
Fig 3C).
DISCUSSION
This systematic review and metaanalysis shows that infants born preterm have a different body composition
at TEA compared with infants born at
term. They have substantially less FFM
with a more similar FM. They have a
greater %TBF that in large part is explained by the lesser FFM rather than an
increase in FM per se. This analysis
supports the findings from other
studies that infants born preterm are
significantly shorter and lighter and
have a smaller head circumference at
TEA than those born at full-term. If
infants born at full-term are used as the
reference against which to compare
intrauterine growth and tissue accretion, then infants born preterm have not
achieved this reference for either
growth or body composition by the time
they reach TEA.
This analysis was limited by the fact
there were few studies in which the
body composition of preterm infants at
TEA was compared with those born fullterm directly. For these studies, the only
consistently reported measure of body
composition was %TBF, with few studies
reporting separate figures for FM or
FFM. The heterogeneity in measures of
composition was high, particularly for
%TBF, which could in part be attributed
to differences in the methods used, the
timing of measurements, and the relative ages of the 2 populations in each
study.
Nevertheless, the meta-analyses for FM
and FFM indicate consistency in the
pattern of body composition seen in
preterm infants at TEA. The differences
between the groups for FM were
modest, ∼50 g, with lack of consistency
across methodologic subgroups. By
contrast, the difference for FFM was
much greater, ∼460 g, and was consistent across all methodologic subgroups. From this, it can be concluded
that the significant difference in body
weight between preterm infants at TEA
and infants born full-term, a mean of
590 g in this study, can be substantially
attributed to a difference in FFM. The
appearance is of a significant constraint on the acquisition of lean tissue
but not on FM. However, without detailed information on the body composition of the preterm infants around
the time of birth, it is not possible to be
sure the extent to which this difference
in FFM can be attributed to poorer intrauterine growth or a limitation in
postnatal accretion of lean tissue. The
relative deficit in FFM in the preterm
group might in part be attributed to
their being significantly shorter at TEA,
but in itself this does not seem adequate to explain the magnitude of the
difference.
An important consideration is the extent to which differences in the pattern
of body composition seen in preterm
infants at TEA have implications for
their health in later life. Previous work
has shown that a low birth weight increases the risk of obesity and noncommunicable disease in adulthood,6,37,38
and preterm birth itself has been associated with an increased risk of hypertension, cardiovascular disease,
and type 2 diabetes.39–42 Alterations in
body composition in terms of both the
relative amounts of fat compared to
lean tissue and the distribution of fat
are likely to disrupt normal patterns
of growth and have also been shown
to affect metabolic function later in
life.37,43 The study by Uthaya et al included in this review demonstrated
that preterm infants at TEA have
altered distribution of fat, with
REVIEW ARTICLE
increased intra-abdominal adiposity
compared with those born at term. 21
In addition, the pattern of growth
seen in this study, with decreased
weight, relatively greater adiposity,
but, most important, a deficit in lean
tissue, has been observed in full-term
Indian babies, where it has been associated with an increased risk of type
2 diabetes and relative adiposity in
later life.44
The mechanisms responsible for the
difference in body composition of preterm infants and the relative paucity of
lean tissue are likely to be multifactorial, with altered body composition representing the final common pathway
for a range of exposures that modulate
the preferred partitioning of nutrients
to lean tissue growth. These include the
availability of an appropriate pattern of
nutrients for growth and other factors
that influence the handling or availability of nutrients, such as concurrent
illness (including infection and lung
disease),hormonalinfluences(including
the use of postnatal corticosteroids),
and the transition from intravenous to
enteral sources of nutrition. The usual
nutrient acquisition of the fetus during
the last trimester of pregnancy is exceptional for any period of life, with
marked lean tissue and adipose deposition together with the acquisition of
hepatic reserves of micronutrients,
such as iron, zinc, and copper. The shift
from nutrient delivery through the
umbilical vein to an enteral intake
through an immature gastrointestinal
tract presents a large challenge, as has
been highlighted in several studies in
this population. Carlson and Ziegler
found that the energy and protein
intakes of preterm infants fell short of
those estimated to be needed to replicate in utero growth.45 By using recommended intakes as a reference,
Embleton et al demonstrated cumulative deficits in protein and energy
intakes in preterm infants during the
PEDIATRICS Volume 130, Number 3, September 2012
first weeks of life that were directly
related to subsequent postnatal growth
restriction.46 These findings are particularly pertinent to the results presented here, as deficits in energy and/
or protein can lead to impaired lean
tissue accretion.47 However, a recent
study by Rochow et al showed that while
increased energy and protein intakes
improved the growth of preterm infants,
there was no significant effect on body
composition at TEA compared with
historic preterm controls.48 Therefore,
additional attention has to be given to
the quality of the protein provided in
the diet and the relative adequacy in
terms of dietary indispensable amino
acids. In turn, the needs for total
nitrogen and the ability of the immature infant to generate conditionally
essential amino acids in sufficient
amounts must also be considered. For
example, we have been interested in
how the fetus/infant generates adequate amounts of glycine, serine, and
cysteine to meet the substantial needs
for net tissue deposition, metabolic
regulation and integration. Using urinary 5-L-oxoproline as a marker for
glycine status in preterm infants
suggests that it may be limiting in
this population.49
Given the complexity of nutritional
needs and their interactions, it seems
likely that no single nutrient alone
constrains the acquisition of lean
tissue in preterm infants but rather a
combination of interrelating factors,
which includes specific nutrient
availability. To date, no studies have
looked in detail at the relationship
between the provision of all macronutrients and micronutrients in the
first weeks after preterm birth and
subsequent growth and body composition at TEA.
CONCLUSIONS
By carrying out a meta-analysis of the
relevant work in this area, this review
has enabled a summary description
of the relationship between preterm
birth and body composition at TEA with
more clarity and confidence. Preterm
infants at TEA are lighter and shorter
and have smaller head circumferences
but, in addition, have a significant
relative deficit in lean tissue. This has
immediate implications in terms of
their functional reserve and susceptibility to ill health and has far-reaching
consequences for their health and risk
of noncommunicable disease in later
life. It is likely that this pattern of body
composition is in part a consequence
of the nutrition that these infants receive while in hospital. More work is
needed looking at the supply of individual nutrients in this vulnerable
group and how this relates to their
growth and body composition at TEA.
Importantly, this study also demonstrates that standard anthropometry
alone is inadequate to fully assess the
growth and nutritional status of preterm infants, suggesting a role for
measures of body composition as
a routine part of growth monitoring.
There is a need to be clearer on the
extent to which these differences in
body composition at TEA should be
attributed to altered intrauterine
growth or postnatal tissue accretion. However, reliable assessment
of body composition during this vulnerable period of rapid change is
challenging, with a lack of practical
and robust methodologies. The development and validation of improved
methods for reliably assessing
body composition in preterm infants
early in life are priorities for understanding and improving their nutritional care.
ACKNOWLEDGMENT
The authors acknowledge the help of Dr
Reginald Annan in reviewing the initial
protocol.
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(Continued from first page)
Address correspondence to Mark J. Johnson, Southampton NIHR Nutrition Diet and Lifestyle Biomedical Research Unit, Southampton Centre for Biomedical
Research, University Hospital Southampton NHS Foundation Trust, Mailpoint 113, Southampton General Hospital, Tremona Road, Southampton, Hants SO16 6YD, UK.
E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2012 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No specific funding was received for this project. However, the authors’ salaries are supported by the National Institute for Health Research (NIHR)
funding to the Southampton Nutrition, Diet and Lifestyle Biomedical Research Unit.
PEDIATRICS Volume 130, Number 3, September 2012
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