Impact of Nutritional and Non-Nutritional Factors on Fat-Free Mass In Very Low Birth Weight Infants PATRICK MCCARTHY, MD CANDIDATE,1 HEATHER GRAY, MPH2 , ELLEN W DEMERATH, PhD2 , MICHAEL GEORGIEFF, MD1 , SARA RAMEL, MD1

1
Impact of Nutritional and Non-Nutritional Factors
on Fat-Free Mass In Very Low Birth Weight Infants
PATRICK MCCARTHY, MD CANDIDATE,1 HEATHER GRAY,
MPH2 , ELLEN W DEMERATH, PhD2 , MICHAEL
GEORGIEFF, MD1 , SARA RAMEL, MD1 1 Department of
Pediatrics, University of Minnesota, Minneapolis,
MN, United States and 2 Department of
Epidemiology and Community Health, University of
Minnesota, Minneapolis, MN, United
States Disclosure statement Dr. Ellen Demerath
has received grant funding from COSMED (Peapod
Manufacturer)

• Protein deficit was not associated with any
  measured growth parameter at either time point.
• Aggressive nutritional support was provided
  resulting in minimal nutritional deficits.
• Inflammation and steroid use affect protein
  accretion and appear to influence FFM accretion
  and linear growth more strongly than intake
  alone. These associations persist until at least
  4 months CA.
• Interventions aimed at decreasing inflammation
  while limiting postnatal steroid administration
  may improve FFM gains and linear growth in this
  vulnerable population.
• Several markers of critical illness/inflammation
  during hospitalization are associated with FFM
  and linear growth both at hospital discharge and
  4 months CA.
• This prolonged effect on growth may reflect
  long-term alterations to the growth hormone/IGF-1
  axis or post-discharge nutritional deficiencies.
• Following adjustment for caloric deficit, only
  steroid administration retained a significant
  impact on growth indices.

Table 3. Association of multiple nutritional and
clinical variables with fat-free mass at
discharge and 4 months corrected age
Table 1. Anthropometric and body composition
characteristics at birth, Hospital discharge and
4 Months CA in 56 AGA VLBW preterm infants
Background While postnatal weight gain is a
concern in preterm infants, organ growth and
differentiation (eg, the brain) is more closely
linked to linear growth and fat-free mass (FFM).
Poor extrauterine linear growth is associated
with lower cognitive function beyond infancy.
Preterm infants have decreased FFM and increased
fat mass at term corrected gestational age
compared to term counterparts. This discrepancy
is thought to be secondary to early nutritional
deprivation and physiological stress, however the
mechanism and long-term consequences of this
altered body composition are not well understood.
Objective This study investigates how early
nutrition and illness in the very low birth
weight (VLBW) neonate affect later body
composition. Design/Methods In this prospective
study, anthropometric measurements and body
composition testing via air displacement
plethysmography were performed on VLBW infants at
hospital discharge (n41 mean discharge age
37.9 /- 2.8 weeks) and at 4 months of age
corrected for prematurity (CA) (n26). During
hospital stay, markers of illness (days requiring
any use of steroids, respiratory support, or
oxygen) as well as macronutrient deficits
(protein and caloric) were recorded. Results At
discharge, greater number of days of steroid
administration was associated with decreased FFM
(p0.001). Increased days of critical illness and
caloric deficit during hospital stay correlated
with significantly lower FFM at 4 months CA
(steroids, p0.04 respiratory support, p0.02
oxygen, p0.03 caloric deficit, p0.01).
Significantly shorter lengths at 4 months CA were
associated with steroid use and caloric deficit.
Neither fat mass nor weight was found to vary
according to any marker of illness or
macronutrient deficit. Protein deficit was not
associated with FFM or length at either time
point. Conclusions FFM, a key marker for organ
growth and development, indexes a number of
clinical factors that reflect the interplay
between critical illness and malnutrition in the
VLBW neonate. The delayed nature of these effects
seen only at 4 months CA may reflect long-term
disruptions to the growth hormone/insulin-like
growth factor-1 axis or insufficient nutrient
intake following discharge. Additional studies
are needed to elucidate the effects of illness on
growth factors and protein accretion in order to
inform nutrition management in VLBW neonates with
particular consideration of FFM.

• Linear growth and fat-free mass (FFM) are closely
  linked to organ development and differentiation
  and are thus important growth parameters for the
  study of nutritional and physiological stressors
  on the preterm infant.
• Preterm infants have elevated fat mass and
  diminished FFM when compared to term counterparts
  at hospital discharge (Ramel et al). Excess early
  growth and body disproportionality may increase
  the risk of adverse neurologic and metabolic
  sequelae. In addition, poor linear growth is
  associated with poor neurocognitive outcomes in
  preterm infants as well as in deprived settings
  globally.
• Factors in addition to nutrient delivery may be
  key to growth optimization in the very low birth
  weight (VLBW) preterm infant. While previous
  research has focused on calorie and protein
  intake, little is known about the impact of
  critical illness and clinical interventions on
  the growth and body composition of this
  population.

Table 4. Association of multiple nutritional and
clinical variables with length at discharge and
4 months corrected age

• FFM and length, key markers of organ growth and
  development, are influenced by energy intake and
  several clinical markers of critical illness and
  inflammation out to at least 4 months CA.
• Postnatal steroid use has an association with
  diminished linear growth and FFM gains well
  beyond the period of administration and
  independent of caloric deficit. This is likely
  secondary to the effect of steroids on protein
  accretion and may be a potential mechanism for
  the association between steroids and poorer
  long-term neurodevelopmental outcomes.
• Additional studies are needed to determine the
  relative contributions of illness and
  malnutrition to growth factors and protein
  accretion to inform nutritional and clinical
  management of VLBW preterm infants.

Table 2. Markers of illness and nutritional
status in 56 AGA VLBW preterm infants
Objective
To investigate how early nutrition and markers of
critical illness in the VLBW neonate affect later
linear growth and body composition.

Figure 2. Relative contributions of illness and
malnutrition on length at Discharge 4 months CA
in AGA VLBW preterm infants
Figure 1. Relative contributions of illness and
malnutrition on FFM at Discharge 4 months CA
in AGA VLBW preterm infants

Length at 4mo CA
Length at Discharge
Fat Free Mass at Discharge
Fat Free Mass at 4mo CA

• SAMPLE 56 appropriate for gestational age VLBW
  (lt1500g) preterm infants
• MEASURES Weight, length, head circumference and
  body composition (fat mass, fat free mass and
  percent body fat) using air-displacement
  plethysmography (Pea Pod, COSMED USA) were
  collected at discharge and at 4 months corrected
  age (CA). Data were also gathered on several
  clinical markers of illness. Total hospital
  caloric and protein deficits were calculated by
  taking the total amounts received throughout
  hospitalization and subtracting it from a
  calculated goal of 120 kcal/kg/day and 3.5 g of
  protein/kg/day, respectively.
• STATISTICAL ANALYSIS Linear regression analysis
  was performed to assess associations between
  indicators of nutritional and clinical stressors
  and growth markers. Adjustment was made for
  infant sex, age at visit, gestational age, and
  kcal deficit depending on the regression model
  used. Individuals with missing data at a time
  point were dropped from analysis at that time
  point.

Ramel SE, Gray H, Larson Ode K, Georgieff M and
Demerath EW. Body Composition Changes in Preterm
Infants Following Hospital Discharge A
Comparison to Term Infants. J Pediatr
Gastroenterol Nutr. 2011 53(3) 333-8. This
study was funded by the Amplatz Scholar Award. We
acknowledge Bridget Davern, Heather Wanous, and
Jenni Super for their assistance in data
collection and enrollment.