Growth Failure in the Preterm Infant: Can We Catch Up?

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Growth Failure in the Preterm Infant:
Can We Catch Up?
Anna M. Dusick*, Brenda B. Poindexter†, Richard A. Ehrenkranz‡, and
James A. Lemons†
Postnatal growth failure is extremely common in the very low birth weight and extremely low birth
weight infant. Recent data from the National Institute of Child and Human Development (NICHD)
Neonatal Research Network indicates that 16% of extremely low birth weight infants are small for
gestational age at birth, but by 36 weeks corrected age, 89% have growth failure. Follow-up at 18 to
22 months corrected age shows that 40% still have weights, lengths, and head circumferences less
than the 10th percentile. Growth failure is associated with an increased risk of poor neurodevelopmental outcome. Inadequate postnatal nutrition is an important factor contributing to growth failure,
as most extremely low birth weight infants experience major protein and energy deficits during the
neonatal intensive care unit hospitalization, in spite of the fact that nutrition sufficient to support
intrauterine growth rates can generally be provided safely. Aggressive nutritional support —parenteral and enteral— is well tolerated in the extremely low birth weight infant and is effective in
improving growth. Continued provision of appropriate nutrition (premature formula or fortified
human milk) is important throughout the neonatal intensive care unit stay. After discharge, nutrientenriched postdischarge formula should be continued for approximately 9 months post-term. Exclusively breast-fed infants require additional supplementation/fortification postdischarge as well.
Additional trials are needed to address a number of important questions concerning the role of
nutrition and growth on ultimate development.
© 2003 Elsevier Inc. All rights reserved.
umerous studies of very low birth weight
(VLBW; less than 1500 g at birth) infants
have shown that the lower the birth weight, then
the smaller the weight, height and head circumference will be in early childhood.1-4 Subnormal
head circumference in infancy has been shown
to be associated with poor cognitive function at
school age, emphasizing the importance of postnatal growth in ultimate neurodevelopmental
function.5 Furthermore, there is compelling evidence that inadequate early nutrition may exert
an adverse influence on postnatal growth and
long-term neurodevelopmental outcome.6 As
many premature infants experience significant
N
From the *Sections of Developmental Pediatrics; and †NeonatalPerinatal Medicine, Indiana University School of Medicine, Indianapolis, IN; and ‡Division of Perinatal Medicine, Yale University
School of Medicine, New Haven, CT.
Address reprint requests to James A. Lemons, MD, James Whitcomb
Riley Hospital for Children, Indiana University School of Medicine,
699 West Dr, RR 208, Indianapolis, IN 46202-5119; e-mail:
[email protected]
© 2003 Elsevier Inc. All rights reserved.
0146-0005/03/2704-0006$30.00/0
doi:10.1016/S0146-0005(03)00044-2
302
energy and nutrient deficits in the first weeks of
life, early growth failure is very common in this
population.7 The potential for catch-up growth,
particularly for the extremely premature infant,
may be limited, recognizing that the factors that
affect the likelihood of catch-up growth are complex, and not limited to nutritional issues.
Therefore, preventing or minimizing growth
failure in the first place may be the most effective strategy to optimizing growth and neurodevelopmental outcome.
In this review, we define postnatal growth
failure in the VLBW and extremely low birth
weight infant (ELBW; birth weight ⬍1000 g),
document the incidence of growth failure in this
population, review the nutrient requirements of
the extremely preterm infant, discuss areas of
nutritional practice that may affect short and
long-term growth and outcome, and identify comorbidities that may influence growth and neurodevelopment. Finally, we identify specific
questions related to nutritional support of the
premature infant that may lend themselves to
investigation in the future.
Seminars in Perinatology, Vol 27, No 4 (August), 2003: pp 302-310
Growth Failure in the Preterm Infant
Growth Failure in the Very Low Birth
Weight Population
As intrauterine growth restriction or small for
gestational age (SGA) is defined as less than the
10th percentile for weight at a given gestational
age, we have similarly defined postnatal growth
failure as body weight less than the tenth percentile for completed weeks of gestation according to the intrauterine growth data reported by
Alexander et al.8 We also used growth parameters less than the 10th percentile for the National Center for Health Statistics (NCHS)
growth standards to define growth failure in
infancy.9
The National Institute for Child and Human
Development (NICHD) Neonatal Research Network reported outcomes of VLBW infants cared
for at 14 participating centers between January
1, 1995 and December 31, 1996.10 The study
cohort was comprised of 4,438 infants weighing
between 501 and 1,500 g. Intrauterine growth
restriction was present in 22% of the cohort at
birth. At 36 weeks corrected age, 97% of the
VLBW population had growth failure with
weight less than the 10th percentile. For those
infants weighing 501 to 1,000 g, growth restriction was present in 17% at birth, but by 36 weeks
corrected age, 99% were less than the 10th percentile (Fig 1).
Additional evidence within the NICHD Neonatal Research Network indicates that there has
been some improvement in early growth in this
population, though it is modest at best. During
2000-2001, 1,433 infants weighing 401 to 1,000 g
Figure 1. Growth of ELBW infants in the Neonatal
Research Network 1995-1996 (n ⫽ 1475). (A) The
mean weight at birth (26 weeks) and at 36 weeks
postmenstrual age; (B) the % SGA at birth (26 weeks)
and at 36 weeks.
303
were enrolled into a randomized trial to determine whether glutamine-supplemented parenteral nutrition decreased mortality or nosocomial sepsis. The study protocol specified
guidelines for early initiation and rapid advancement of parenteral nutrition, particularly amino
acid intake. In this study 16% of infants were
identified as growth-restricted at birth. At 36
weeks corrected age (CA), 89% of infants had
growth failure. This represents a reduction from
99% growth failure seen in the ELBW population in 1995-1996 to 89% in 2000-2001, a decrease of 10%. Although a modest improvement, the prevalence of postnatal growth failure
in the ELBW infant in the NICU remains exceedingly high.
Is growth failure in the NICU associated with
longer term growth failure and/or neurodevelopmental deficit? In a study of 1,527 ELBW infants born between January 1993 and December
1994 within the NICHD Neonatal Research Network, Dusick et al11 hypothesized that the incidence and severity of early childhood growth
failure and impaired neurodevelopmental outcome would increase with neonatal growth failure. The study included follow-up of all ELBW
infants with a uniform protocol at 18 to 22
months CA.12 Anthropometric measures were
plotted according to gender and corrected age
at examination using standard NCHS data. The
1979 NCHS data were used as they were considered the standard at the time the current study
cohort were born and analyzed (1993-1994), although newer NCHS standards are now available. Further, the weight-length ratio as an indicator of acute body fat stores was also plotted,
using the NCHS data. Poor growth was defined
as weight-length ratio less than or equal to the
10th percentile.
Data were managed and analyzed at the
George Washington University Biostatistics Coordinating Center. Categorical variables of
⬍10th percentile, 10th-90th percentile and
⬎90th percentile were used throughout the
analysis (consistent with the classification of
birth weights ⬍10th percentile [SGA status],
weight ⬍10th percentile at 36 weeks) and for
clinical association. The Chi square analysis was
used for categorical variables between SGA versus appropriate birth weight for gestational age
(AGA) infants, and between genders. Data were
also analyzed in 100-g birth weight intervals to
304
Dusick et al
Figure 2. Median, 5th percentile, and 95th percentile
for weight at follow-up as compared to the NCHS
growth curves.
examine differences or similarities between
groups of ELBW infants and clinical categorical
variables. Analysis of variance was used for continuous variables. Associations to poor growth
were identified. Univariate analyses were done
for known factors and significant associations
were included in the logistic regressions for
poor growth.
The follow-up cohort included 1,151 ELBW
survivors who were evaluated at 18 to 22 months
CA; 47 or 3% died after initial hospital discharge, and 329 or 22% were lost to follow-up.
There was no difference in birth weight, gestational age, incidence of intracranial hemorrhage, periventricular leukomalacia, or days of
ventilation between the cohorts seen and the
group that survived but that was lost to follow-up.
The weight, length, and head circumference
measures obtained at the follow-up examination
were compared to the NCHS growth grids. Figure 2 represents the median and range of weight
in the cohort at 18 to 22 months CA. Median
weight was between the 10th and 25th percentiles in each gender. Similarly, the median
lengths and head circumferences also fell between the 10th and 25th percentiles. Figure 3
presents the percent of the cohort that weighed
less than the 10th percentile at birth, at 36 weeks
postmenstrual age, and at 18 to 22 months CA,
by 100-g birth weight groups. At birth, greater
than 70% of those who weighed 401 to 500 g and
34% of those who weighed 501 to 600 g were less
than the 10th percentile. Among the 601- to
1,000-g groups, 15% to 18% were less than the
10th percentile for weight at birth, but by 36
weeks 98% to 99% of the entire cohort was less
than 10th percentile (similar to 1995-1996 and
2000-2001 ELBW infants). By the time of the
follow-up visit, many of the children in the 601to 1,000-g birth weight group displayed catch-up
weight growth after 36 weeks, although 40% of
this group still had weights less than the 10th
percentile.
Do SGA infants experience more postnatal
growth failure than AGA infants? At birth, 18%
of the infants were SGA. At 18 to 22 months CA,
significantly more children born SGA than AGA
were below the 10th percentile for all 3 growth
parameters: weight 69% v 42%, P ⬍ .0001;
length 62% v 39%, P ⬍ .0001; head circumference 60% v 40%, P ⬍.0001; and weight-length
ratio 51% v 31%, P ⬍.0001 (Fig 4). Therefore, in
utero growth restriction for infants born weighing less than 1,000 g is associated with a greater
incidence of postnatal growth failure, including
head circumference, than for infants who are
AGA.
It is evident that the risk of growth failure is
inversely related to birth weight. As seen in Figure 5, when infants are examined by 100-g birth
Figure 3. Comparison of weight ⬍10th percentile on the NCHS growth data charts corrected for prematurity,
gender and age at follow-up for birth weight groups in 100 g intervals at three time points: birth, 36 weeks and
follow-up (18-22 months corrected age).
Growth Failure in the Preterm Infant
Figure 4. Comparison of growth at 18 months according to SGA vs. AGA status at birth.
weight groups, the incidence of growth failure in
weight, length and head circumference increases as weight decreases. For the 901- to
1,000-g group, approximately one third had
weight, length, and head circumference less
than the 10th percentile at 18 to 22 months CA.
In contrast, approximately 70% of infants weighing 501 to 600 g had a weight, length, and head
circumference less than the 10th percentile at 18
to 22 months CA.
While intrauterine growth restriction and
lower birth weight group are correlated with
growth failure, are other neonatal morbidities
predictive of poor growth? In analyzing for other
risk factors, logistic regression analysis conducted by using race, male gender, grade III/IV
intracranial hemorrhage/periventricular leukomalacia, chronic lung disease, antenatal steroid therapy, and postnatal steroid therapy for
chronic lung disease. Significant predictive factors for increased risk of growth failure at 18 to
22 months CA included white race and grade
305
III/IV intracranial hemorrhage/perventricular
leukomalacia. Postdischarge factors were also examined for an association with poor growth,
using logistic regression analysis. Variables included in the analysis were oxygen at 18 months
CA, use of bronchodilators at 18 months CA,
tracheostomy, mechanical ventilation at home,
rehospitalization more than 3 times, abnormal
swallowing, abnormal neurologic examination,
and a primary caregiver with less than a high
school degree. Significant postdischarge risk factors for poor growth at 18 months CA included
an abnormal swallow and an abnormal neurologic examination.
Is there an association between poor postnatal growth and neurodevelopmental outcome? A
small head circumference (⬍5th percentile) at
follow-up was examined as a risk factor for poor
neurodevelopmental outcome using the Mental
Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) of the Bayley
Scales of Infant Development-II.13 A small head
circumference, as well as a weight-length ratio
⬍10th percentile), were associated with significantly lower MDI and PDI scores (personal communication, June 2001).
In summary, the ELBW population continues
to have an extremely high incidence of growth
failure in-hospital, which is associated with a
high rate of growth failure at approximately 2
years of age and poorer neurodevelopmental
outcome. Also consistent with previous studies,
the lower the birth weight group in this ELBW
cohort, the less likely the infant is to achieve
Figure 5. Comparison of growth at 18 months that is ⬍10%, 10-90%, or ⬎90% according to birth weight group
in 100 g intervals. NCHS growth percentile data are used that correct for gender and the exact age at follow-up
18-22 months of corrected age.
306
Dusick et al
catch-up growth in early childhood.14,15 We examined the relationships of neonatal factors and
factors present at 18 months CA in relationship
to poor weight-length ratios at follow-up, and
like others, we found SGA to be significantly
related to later poor growth.3,12,15-17 Independent neonatal factors also included IVH grades
III and IV, and white race. An abnormal neurologic exam and having an abnormal swallow
were associated post-discharge factors identified
at 18 to 22 months CA in our study. Chronic
lung disease and long-term oxygen use were not
predictors of poor growth. This is in contrast to
the observation of chronic lung disease as a
factor in poor growth of the hospitalized VLBW
infant prior to initial discharge.7,18 Kelleher et
al19 evaluated several psychosocial factors in the
assessment of failure to thrive in premature infants. They reported that the mother’s education level, or father in the home, were associated
with weight less than the 5th percentile. In our
data, the primary caregiver’s education level did
not show an association with poor growth, suggesting that the nonenvironmental causes for
poor growth may be stronger in the ELBW
group in this early childhood period. Poor
growth may be the result of a complex interaction of a number of factors, including inadequate nutrition, morbidities affecting energy requirements, endocrine abnormalities, central
nervous system insults, medications that may affect protein and energy metabolism, and others.
While inadequate nutrition itself may impact
brain maturation and growth during a vulnerable period, it may also more broadly affect
health by compromising other organ maturation, impairing immune function, and diminishing reserves for recovery from chronic or intercurrent illness or surgery.
Nutrient Requirements of the Extremely
Low Birth Weight Infant
Until relatively recently, little information has
been available regarding the energy and nutrient requirements of the ELBW infant, particularly early in postnatal life. This lack of data was
due in large part to technical challenges in performing such studies. However, in the last several years, the energy, protein and other macronutrient requirements of the extremely preterm
infant have been defined in considerable detail.6
The basal energy expenditure of the relatively
stable ELBW infant in the first week of life has
been found to be ⬃60 to 80 kcal/kg/day.19,20
This is considerably higher than had been previously thought, and in fact, is greater than the
basal energy requirement of full-term infants
with severe respiratory distress. Based on these
data, approximately 70 kcal/kg/day will meet
basal requirements, but will not be sufficient to
support growth in this population.
The glucose requirement of the extremely
low birth weight infant is 8 to 10 mg/kg/minute
or ⬃11-14 g/kg/day (44-56 cal).21 This amount
of glucose can easily be delivered as a 7.5% to
12.5% dextrose solution, depending on the intravenous fluid rate. The balance of nonprotein
calories can be provided as intravenous lipid.
Several studies have documented that intravenous lipid, given at 3 g/kg/day (27 cal/kg/day),
is well tolerated without elevations in triglyceride or free fatty acid.22-27 Additionally, no adverse affect on chronic lung disease or mortality
has been found.
Perhaps even more striking is the protein
requirement for the ELBW infant in early postnatal life. This is approximately 4 g/kg/day, and
is very similar to that of the growing fetus at the
same gestational age (3.6-4.8 g/kg/day).6 Protein accretion increases linearly with protein or
amino acid intakes ranging from 0.5 to 4.0
g/kg/day, depending on provision of adequate
nonprotein energy.28 However, if ELBW infants
are given no protein and only receive glucose (a
common practice in the first days of postnatal
life), they will lose in excess of 1.5 g/kg/day of
body protein. As depicted in Figure 6, a 1,000-g
infant born at 26 weeks’ gestation has approximately 88 g total body protein. If that infant is
simply provided glucose postnatally, the baby
will lose approximately 1.6 g of protein per day.
At the end of seven days, this will result in the
absolute loss of 11.2 g of protein, or approximately 13% of the body stores. Had the infant
remained in utero, the baby would have accrued
1.8 g of protein per day, or 12.6 g over a 7-day
period. Therefore, for an infant who is provided
only glucose for the first week postnatally, the
protein deficit by 7 days would be 25% of the
body protein the baby would have had in utero.
Such a deficit is almost impossible to recoup.
Can provision of amino acids parenterally
prevent a negative protein balance? In fact, pro-
Growth Failure in the Preterm Infant
Figure 6. Change in body protein over the first 7 days
of postnatal life for a 1000g, 26wk gestation infant
provided just glucose vs in utero.
vision of 1.5 g/kg/day of amino acid with as little
as 30 to 40 kilocalories of energy will result in
slightly positive protein balance.29 To achieve in
utero protein accretion rates, approximately
3.5 g of amino acid is required parenterally.
Appropriate nonprotein energy intake (⬃90
kcal/kg/day) would also be necessary to support
this rate of growth.
Can parenteral nutrition be provided to the
ELBW infant in the first days of life safely and
effectively at levels which will promote growth?
Numerous studies have shown that provision of
amino acids, even at levels up to 3 g/kg/day
within 24 hours of age are well tolerated by the
ELBW infant without any reported adverse affects.30-32 The blood urea nitrogen (BUN), pH,
and ammonia levels are normal and comparable
to control infants not receiving amino acids. The
provision of 3.5 g/kg/day of amino acid with 90
kcal/kg/day of energy intake as carbohydrate,
amino acid, and lipid have been demonstrated
to effect a positive nitrogen balance equivalent
to in utero expectations.
Therefore, the evidence is compelling that
the extremely low birth weight infant should be
given parenteral nutrition beginning on day 1,
and advanced rapidly over the first days of postnatal life to provide approximately 90 cal/kg/
day with 3.5 g/kg/day of amino acid.
When should feedings be initiated in this
population? Numerous randomized trials of
minimal enteral intake or trophic feedings have
been reported, as well as a Cochrane Review of
307
those studies.33 Results indicate that minimal
enteral feedings of approximately 20 mL/kg/
day of half to full strength formula or breast milk
are well tolerated in the first days of life, and are
associated with both improved physiologic and
clinical outcomes. Physiologically, such feedings
are associated with prevention of intestinal atrophy, enhanced intestinal motility, decreased
intestinal permeability, increase in intestinal trophic hormones, and increase in lactase concentration. Clinically, minimal enteral intake resulted in shortened time to full enteral feedings
and substantial reduction in total length of hospital stay. There were no adverse effects, and the
incidence of necrotizing enterocolitis was not
increased. Minimal enteral feedings were well
tolerated in infants who had umbilical arterial
catheters in place, as well. Therefore, there appears to be compelling evidence to support the
initiation of minimal enteral feedings shortly
after birth, as they are effective and safe.
Does an aggressive approach to nutritional
support of the extremely low birth weight infant
affect growth in the NICU? A randomized trial
of an aggressive nutritional regimen in this population was performed by Wilson et al.27 Their
results indicated that the use of aggressive nutrition, both parenteral and enteral, was well tolerated and safe in the preterm infant. The group
assigned to receive the more aggressive nutritional regimen had less initial weight loss, significantly shorter time to regain birth weight, and
significantly fewer infants experiencing growth
failure in the NICU. Eighty-two percent of control infants were less than the 10th percentile for
weight at the time of discharge or death, in
contrast to 59% of infants in the group provided
more aggressive nutritional support. Similarly,
57% of control infants had a length less than the
3rd percentile at discharge or death, in contrast
to 33% of the infants with more aggressive nutritional support. Further, the percent of infants
with head circumference less than the 10th percentile at discharge was reduced significantly in
the group supported with more aggressive nutrition. These data again support the safety and
efficacy of a more aggressive nutritional approach to this population, particularly early after
birth.
Has this evidence that more aggressive parenteral and enteral nutrition for the extremely low
birth weight population been translated into
308
Dusick et al
practice? Although difficult to answer, some data
are available which suggest that, while there has
been improvement in nutritional support of the
ELBW infant, we still have a long way to go.
Several markers of nutritional support are collected for all ELBW infants cared for within the
Neonatal Research Network. Approximately
1,500 infants weighing less than 1000 g are cared
for within the Network centers each year. In
1997, the day of first parenteral nutrition was
2.5 ⫾ 3.0; in 2001, it was 1.7 ⫾ 2.3. Parenteral
nutrition is initiated earlier now than it was 5
years previously, although for the majority of
infants it is not started until the second day of
life and for a significant minority, it is not started
for several days or longer. The first enteral feeding was provided in 1997 on day 6.8 ⫾ 6.5; in
2001, it was day 4.7 ⫾ 6.0. Again, there has been
some improvement, but current evidence suggests that enteral feedings should be initiated in
the large majority of infants on day 1. The first
day at which full enteral feedings was achieved
was day 25.3 ⫾ 15.6 in 1997, and 19.3 ⫾ 15.1 in
2001, an improvement of 6 days. These markers
of nutritional support are associated with another marker of growth in the NICU, the day at
which babies regain birth weight. In 1997, ELBW
infants regained their birth weight by day 16.2 ⫾
7.6, and in 2001 by day 12.5 ⫾ 6.6. Therefore,
earlier provision of nutrition, presumably at
higher caloric and nutrient intakes, appears to
be associated with improved growth in the
NICU. This is further evidence that more aggressive nutritional support is appropriate and effective in improving growth outcomes.
Full enteral nutrition in the form of appropriate premature formulas and/or fortified human milk should be continued throughout the
hospitalization. Frequent monitoring of growth
with daily weights and weekly lengths and head
circumferences should be routine practice. Plotting these anthropometric measures on growth
grids is an important and convenient way of
monitoring growth and ensuring that infants are
receiving necessary caloric and nutrient intake.7
While the “average” 26-week gestation infant
may require approximately 120 cal/kg/day to
sustain intrauterine growth rates, the range is
wide. Intrauterine growth-restricted infants
and/or those experiencing significant catch-up
growth may require 160-200 kcal/kg/day.
Should ELBW infants receive calorie and pro-
tein supplements after discharge? Several studies
now suggest that the growth of the extremely
preterm infant may be improved by the provision of nutrient-enriched formula during infancy. Carver et al34 performed a randomized
trial of preterm infants who were fed a 22 cal/oz
nutrient-enriched postdischarge formula or a
standard 20 cal/oz term infant formula after
discharge to 12 months CA. In a subgroup analysis of infants less than 1,250 g at birth, those fed
the enriched formula weighed more than the
control infants at 6 months CA, were longer at 6
months CA, and had larger head circumferences
at term, 1, 3, 6, and 12 months CA. In a similar
trial by Lucas, et al., preterm infants were randomized to an enriched post-discharge formula
or standard term formula or breast milk for 9
months post-term.35 Results indicated that those
infants fed the enriched formula were heavier
and longer at 9 months, although there was no
effect on head circumference. There was no
significant difference in developmental scores at
9 to 18 months. At 6 weeks post-term, exclusively
breastfed infants were more than 500 g lighter
and 1.6 cm shorter than the group fed the enriched formula, and they remained smaller up to
9 months post-term. These findings again support the use of an enriched formula for preterm
infants for at least 9 months post-discharge. In
addition, these findings suggest that small preterm infants who are exclusively breast-fed may
require additional supplementation or fortification postdischarge.
Questions for Future Research
While aggressive early parenteral and enteral
nutrition appears to be an effective and safe
strategy for supporting ELBW infants, further
refinements in the profile of amino acids and
other nutrients are likely to be needed. Defining
the exact amino acid requirements and ensuring
that they are presented in proper balance in
parenteral nutrition solutions remains an important issue. It is critical that adequate amounts of
all essential amino acids are provided, but currently we do not know if specific amino acids are
present in concentrations which may be rate
limiting for growth.
Additional studies are necessary to assess the
role of nutrition and growth in early postnatal
life, during hospitalization, and postdischarge
Growth Failure in the Preterm Infant
on neurodevelopment. Several studies suggest
that the quantity, as well as the quality of enteral
nutrient provided to preterm infants during
their initial hospitalization may influence ultimate neurodevelopment and intelligence quotients in childhood.36-39 These results need to be
confirmed by additional randomized trials.
Such findings of altered neurodevelopmental
outcome in childhood associated with a nutritional intervention in neonatal life are consistent with the Barker hypothesis, or fetal origins
of adult disease.40 A number of epidemiologic
studies have provided evidence in both humans
and animals that adult cardiovascular disease,
hypertension, diabetes, and hypercholesterolemia may be linked to fetal growth restriction.
The process whereby a stimulus or insult at a
sensitive or critical period of development has
long-term effects is termed “programming.” As a
fetus undergoes some adaptation to an insult or
nutritional deficiency, the physiology of the fetus may become programmed or altered permanently, eventually manifesting as adult onset disease. Do ELBW infants with intrauterine growth
restriction and/or postnatal growth restriction
manifest abnormalities in insulin sensitivity, cardiovascular function, and/or lipid metabolism
in infancy or early childhood, and ultimately in
adulthood? If so, what is the mechanism responsible for these changes?
How much catch-up growth is possible, and
over what time frame, for intrauterine growthrestricted and/or postnatal growth-restricted infants? And does catch-up growth improve neurodevelopmental outcome? Does catch-up
growth decrease the risk of adult onset diseases?
While we assume that catch-up growth is beneficial, this has not been confirmed by appropriate
clinical trials.
Summary
Postnatal growth failure occurs in the vast majority of ELBW infants. While the pathogenesis
of such growth failure is clearly multifaceted,
inadequate nutritional support is a significant
factor–and one that we can address. We know a
great deal more about what constitutes safe and
effective nutrition for these infants than we did
10 years ago. Nonetheless, translating that
knowledge into practice remains a challenge.
309
Acknowledgment
We especially thank the Follow-up Principal Investigators and Follow-up Coordinators of the NICHD Neonatal Research Network.
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