Brain Injury in Moderate Preterm Neonates

Annually in the Netherlands 14.000 neonates are born prematurely at a
gestational age (GA) less than 37 weeks. Very preterm neonates (GA < 32 weeks)
are at risk of brain injury, acquired during the perinatal and neonatal period.
This is strongly related to neurological impairment, including motor and
cognitive deficits, sensorineural hearing loss, cerebral visual impairment and
behavioural problems.
The vast majority (80%) of preterm neonates, however, is born moderately
prematurely (GA 32-37 weeks). Only since recently it is known that they also
have an increased risk for disabilities, as compared to healthy, full term
neonates. It may be assumed that these disabilities are related to brain
injury, acquired during the perinatal and/or neonatal period. This has,
however, never been investigated: little is known about the prevalence,
characteristics and consequences of brain injury in the much larger group of
moderate preterm neonates.
Almost all knowledge about preterm brain injury is obtained from extensive
research performed in the very preterm population. The disabilities in these
children related to perinatal and/or neonatal brain injury are not only a
problem for the individual child and its family but, due the immense costs,
also for the society. In the Netherlands the estimated annual costs, needed for
the care of disabled very preterm children is about ¤11.000.000. This excludes
the much higher institutional costs. Since many decennia medical care for very
preterm neonates is highly centralized: immediately after birth these
vulnerable infants are admitted to a Neonatal Intensive Care Unit (NICU) and
undergo highly specialized medical and nursing care. To enable early detection
of brain injury, very preterm infants undergo neuro-imaging, consisting of
serial cranial ultrasound (cUS) examinations from birth until term equivalent
age (TEA) and in many cases also an MRI-examination around TEA. In addition,
after discharge, they undergo standardized follow-up programs, enabling early
diagnosis of neurological impairment and thus early interventions (such as
physiotherapy, speech therapy, hearing aid, physical rehabilitation, visual
rehabilitation). In very preterm neonates these early interventions are
successful for prevention of (serious) disabilities and improving functional
outcome.
The much larger group of moderate preterm infants is also at risk of
disabilities and abnormal neurological development. They have a 2-fold higher
prevalence of developmental delay, more problems with fine motor skills,
communication, and personal-social functioning at preschool age, and more grade
retention and need for special educational at school age than full term
children. In adulthood they perform less.
In contrast to very preterm infants, moderate preterm infants are not admitted
to a NICU, but to neonatal wards of general hospitals. They receive far less
specialized care and do not routinely undergo neuro-imaging examinations or
standard follow-up programs.
As the group of moderate preterm children is so much larger than the group of
very preterm children, the economic and social consequences of even a slightly
increased risk of abnormal outcome are probably much larger than for the very
preterm group. Knowledge about perinatal/neonatal brain injury and its
consequences is essential for prevention and treatment strategies. This may
lead to better functional outcomes and thus significant reduction of health
care costs.

To assess in moderate preterm infants:
1) The prevalence and characteristics of brain injury;
2) The relation between perinatal factors and brain injury;
3) The validity of cUS for detection of brain injury as compared to MRI
(considered the golden standard);
4) The relation between neurological examination at TEA and brain injury;
5) The relation between neurodevelopmental outcome at 2 years of age and brain
injury.

A prospective, longitudinal observational neuro-imaging study.

There is no risk associated with study participation.
The neuro-imaging techniques we will apply are safe and non-invasive and the
neonatal team has ample experience with both techniques. cUS is performed at
the bedside with little disturbance to the infant. It has routinely been used
worldwide since the early eighties to detect brain injury in very preterm and
other high-risk neonates. It is safe and reliable for the detection of many
forms of neonatal brain injury.
MR imaging of the brain has been applied in many NICUs since the nineties for
more precise and reliable detection of brain anomalies in high-risk neonatal
populations. It gives detailed and additional information on the exact site and
extent of lesions and on brain maturation. It therefore further helps to
prognosticate. MRI is biologically harmless. No short- or long-term adverse
effects from MRI at field strengths and durations clinically used have been
identified to date. MRI will be performed at TEA during natural sleep, shortly
after a feed. We will bundle the infants prior to the MRI examinations and will
not apply sedation. Ear protection, specially designed for neonatal MRI at
3-Tesla field strength will be provided. Infants will be guided through the
whole procedure, including transportation to and from the MR department by a
neonatologist or nurse-practioner experienced in neonatal MRI procedures and
neonatal resuscitation. All standard safety precautions, including MRI
compatible monitoring of heart rate and oxygen saturation for neonatal MRI will
be followed.There is a small burden related to the MRI procedure, as the
infants need to be admitted for * day.
Participation in this study may lead to early detection of major brain
abnormalities. We will not inform parents on the brain imaging findings, with
the exception of parents of infants with major brain abnormalities that will
likely have severe consequences for outcome (such as cerebral palsy and severe
cognitive impairment) and for which early interventions are likely to improve
outcome. As early interventions can thus be initiated, this may be beneficial
for the individual child.
If a higher prevalence of brain injury is found in moderately preterm neonates
as compared to full term neonates38-44, screening for brain injury is indicated
in this patient group. This will lead to early detection of brain abnormality.
On the long term the study may therefore contribute to better health of
moderate preterm children and may thus be beneficial for this specific group
and the society