: Long-term follow up of growth and bone mineralization of former preterm infants

The survival of preterm infants has improved in recent years, but former
preterm infants have a reduced length and bone density in later life compared
to peers born at term.
As a fetus accrues two-thirds of its total calcium during the last trimester,
infants who are born before that time are deprived of this mineral
accumulation. After birth it is difficult to maintain a comparable intake of
minerals, because of several factors, such as low mineral reserves, increased
requirements, medication and increased rate of bone resorption. Adequate early
nutrition is important for adequate intake of minerals, particularly calcium
and phosphate. The inadequate provision of nutrients after birth and the
increased bone resorption probably lead to the development of metabolic bone
disease of prematurity.

In 2005 the composition of the standard parenteral nutrition for preterm
infants used at the department of neonatology of the Radboud University Medical
Centre (RUMC) was changed, according to international recommendations at that
time, to improve postnatal growth and development of very low birth weight
infants. Besides an improved protein and energy intake, the new parenteral
solution provided a significant increased amount of calcium and phosphate.

As a quality control, we performed a retrospective cohort study of data of
patients admitted to the NICU on the first day of life (cmo-nr 2009/323). The
data of two cohorts were compared. The first cohort contained infants admitted
during 2004, receiving the old standard composition of parenteral nutrition,
while the second cohort (2005) received the new composition of parenteral
nutrition. Nutritional intake, growth and laboratory results were registered
according to the standard procedures of the department daily during the first
two weeks, weekly until week 5, at term age and during standard follow up at
age of two and five years.

Analysis of these data showed that the children born in 2005 at the age of 2
years tended to demonstrate a better catch-up growth in length compared to the
children born in 2004. It is not known whether this improved length has
sustained until school age and if the bone density has improved significantly.
We therefore designed this study to evaluate growth and bone mineralization of
the former cohorts.

We hypothesize that the former preterm infants, born in 2005 with high calcium
and phosphate intake, nowadays at the age of 8-10 years have an improved bone
mineralization and length compared to the preterm infants, born in 2004 with
less calcium and phosphate intake (2004 group).
To determine bone mineralization we will perform a Dual-energy X-ray
absorptiometry (DEXA) scan and quantitative ultrasound (QUS).

To determine whether increased calcium and phosphate intake (2005 group)
resulted in improved Bone Mineral Content (BMC) and Bone Mineral Density (BMD)
compared to the group with less calcium and phosphate intake (2004 group) at
the age of 8-10 years, determined by DEXA scan.
Secondary objective of the study: To determine whether increased postnatal
calcium and phosphate intake (group 2005) compared to lower postnatal calcium
and phosphate intake (group 2004) at the age of 8-10 years results in:
- improved BTT (bone transit time = speed of sound) with quantitative
ultrasound
- improved length, weight, head circumference

Observational study

Parameters used as primary endpoint (DEXA-scan, quantitative ultrasound (tibial
speed of sound) are not invasive and not painful. The radiation exposure of a
DEXA scan can be considered as a very low dose. This method is seen as golden
standard for determination of bone mineral content in children. The
quantitative ultrasound, measuring the speed of sound is a quick, simple
non-invasive procedure that can be used to evaluate skeletal development.