Cerebral Palsy, Developmental Coordination

Disorder, Visual and Hearing Impairments in

Infants Born Preterm
Krishna Acharya, MBBS, MPH,* Matthew Pellerite, MD, Joanne Lagatta, MD, MS,* Bree Andrews, MD, MPH,
Michael E. Msall, MD
*Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.

Department of Pediatrics, University of Chicago Medicine-Comer Childrens Hospital, Chicago, IL.

Educational Gaps
1. Clinicians need to recognize children who are at risk for moderate and
severe motor and neurosensory impairments to ensure early referral for
appropriate services.
2. Clinicians need to understand that children with cerebral palsy fall on a
wide spectrum of severity and many will have good overall functioning
with appropriate therapies and developmental supports.

Abstract
Motor disabilities and neurosensory impairments are common in survivors of
prematurity, and signicantly affect quality of life. Cerebral palsy occurs with
a much higher prevalence in preterm survivors compared with term infants;
however, another less severe but important neuromotor condition is
developmental coordination disorder. Visual and hearing impairments are
less common, but signicantly compound physical disabilities. Early
identication and referral for services are important to optimize functioning,
learning, and community supports for these children. This article provides a
review of prevalence, at-risk factors, presenting signs and symptoms, and
management strategies for these conditions.

Objectives After reading this article, readers should be able to:

1. Describe the prevalence of cerebral palsy (CP), developmental

coordination disorder (DCD), and visual and hearing impairments.
2. Understand the early risk factors that contribute to these conditions.
3. Recognize presenting signs of CP and DCD as well as poor prognostic
indicators.
AUTHOR DISCLOSURE Drs Acharya, Pellerite,
Lagatta, Andrews, and Msall have disclosed no 4. Understand the current management strategies for children with these
nancial relationships relevant to this article.
conditions.
This commentary does not contain a
discussion of an unapproved/investigative
use of a commercial product/device.

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 INTRODUCTION At-Risk Infants
Prematurity is the strongest predictor of CP. (10) In the
Preterm birth is associated with a broad spectrum of devel-
National Institute of Child Health and Human Develop-
opmental challenges. Motor difculties, specically cere-
ment Neonatal Research Network, the prevalence of mod-
bral palsy (CP), are well-known, but other motor, cognitive,
erate to severe CP (dened as those who are nonambulatory
communicative, behavioral, learning and sensory disorders
or require an assistive device for ambulation at 1822
are more common, occurring in 25% to 50% of extremely
months of age) was 10.4% to 12.1% for infants born at 22
premature infants. (1)(2)(3) Premature infants (<37 weeks)
to 26 weeks gestation and 6.3% to 7.8% for infants born
constitute about 12% of all live births, and extremely pre-
at 27 to 32 weeks gestation. (11) Studies have suggested
mature infants (<28 weeks) constitute 0.8% of all live
improved neurodevelopmental outcomes in extremely pre-
births. (4) With the increasing survival of extremely pre-
mature infants. (12) However, most studies show no signif-
mature infants and with many infants now being resusci-
icant improvement in prevalence of CP among infants who
tated at 22 weeks gestation, the developmental follow-up
are born at less than 25 weeks gestation, with a CP prev-
of these infants at key developmental ages becomes para-
alence as high as 15% to 20%. (13)
mount. Follow-up of at-risk children is important to ensure
A large prospective population-based study from France
timely intervention and ongoing services, with a focus on
(EPIPAGE)(10) showed that among infants with less than
optimizing functioning and participation. In addition, not
26 weeks of gestation, the incidence of CP was 10% even
all motor and sensory issues may be noted at the rst de-
with normal head ultrasound (HUS) ndings and 20% or
velopmental evaluation, so children require continued mon-
higher with any form of intraventricular hemorrhage (IVH).
itoring through school entry to promote their success.
The study showed the following for any given abnormality
on HUS: (1) the rates of CP were signicantly higher for
CEREBRAL PALSY infants who had less than 26 weeks of gestation compared
with those born at 27 to 32 weeks of gestation except for
CP describes a group of permanent disorders of the de-
those who had periventricular leukomalacia (PVL) or intra-
velopment of movement and posture, causing activity
parenchymal hemorrhage (IPH); (2) between 27 and 32
limitations, which are attributed to non-progressive dis-
weeks gestation, infants at the lower gestational ages did
turbances that occurred in the developing fetal or infant
not have higher CP rates for the same HUS nding. In
brain. The motor disorders of CP are often accompanied by
short, for the infant who has the most severe form of brain
disturbances of sensation, perception, cognition, commu-
injury in the form of PVL or IPH, gestational age did not
nication, and behavior; by epilepsy; and by secondary
affect CP risk (40%60%). But for any other form of IVH
musculoskeletal problems.(3) It is important to note that:
(including grade 3), the smallest infants (<26 weeks) had
(1) CP is a clinical description, not diagnosis, and lacks
worse outcomes than those who had more than 27 weeks of
specic pathologic or radiographic features; some infants
gestation.
with CP have normal ndings on brain magnetic reso-
In addition to prematurity, multiple gestation, exposure to
nance imaging (MRI); (2) its onset occurs early in life,
postnatal steroids, need for high-frequency ventilation, pro-
either during the perinatal period or infancy, but diagnosis
longed mechanical ventilation, pneumothorax, male gender,
was historically reserved until 24 months of age (3); and (3)
sepsis, necrotizing enterocolitis, African American race, and
although the brain injury is nonprogressive, secondary
low socioeconomic status are all risk factors for CP. (14)(15)
impairments can change over time and include a spectrum
of challenges in cognitive, communicative, manipulative,
and social functioning. (5)
Infants Who Are Not Identied
Although prematurity posits a strong risk for developing CP,
Prevalence half of all cases of CP occur in term infants. (16) Among
CP is the most common physical disability in childhood. (5) term infants, in-utero factors pose a greater risk in the
The prevalence of CP in developed countries is estimated to outcome of CP than perinatal or postnatal factors. (17)(18)
be 1.5 to 2.5 per 1,000 live births, but as high as 3.8 per 1,000 Among maternal factors, chorioamnionitis, maternal intel-
live births in some US regions. (6)(7) There is some lectual disability, hypothyroidism, and severe proteinuria
evidence of increasing prevalence of CP, likely due to the increase the risk for CP. Among infant factors, ischemic
increasing survival of extremely premature and very pre- stroke, neonatal encephalopathy, noncentral nervous sys-
mature infants. (8)(9) tem malformations, cerebral dysgenesis, 5-minute Apgar

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score of less than or equal to 3, intrauterine growth restric-
tion, birthweight less than 2,000 g, severe hyperbilirubine-
mia, and male gender are associated with CP. (18)(19)(20)
(21)(22) Although infants with cerebral malformations or
seizures during the neonatal period are usually followed in
developmental clinics, well-appearing infants with mild motor
delays and antecedent risk factors such as chorioamnionitis
may not receive close developmental follow-up, especially
if their neonatal course is uncomplicated.
Identication of Cerebral Palsy
Although a diagnosis of CP is typically not made until age 2
years, infants can exhibit early signs. In the young infant (<1
year of age), hyper- or hypotonia, difculty with advancing
oral feeds, hand preference, prominent sting, asymmetric
crawling, persistence of primitive reexes, ankle clonus, and
scissoring of legs are important early signs. (23) In addition,
they may exhibit abnormal behavior in the form of excessive
crying, jitteriness, abnormal sleeping patterns, and irrita-
bility. (24) The quality of general movements (spontaneous
motor activity of the infant) in a young infant is predictive of
motor impairment with cramped-synchronized movements
being predictive of CP. (25) Infants with micro- or macro-
cephaly, seizures, multiple apneic episodes, need for gavage
feeds, temperature dysregulation, and 10-minute Apgar
score of less than 3 are at high risk for CP. (26)
Management Strategies
If a child has severe motor impairment and high clinical
suspicion (eg, PVL on MRI), the diagnosis of CP can be
made before age 2 years. In Australia, a strategy to identify
children at highest risk for CP in the rst 4 months after
birth combines neuroimaging and general movement
assessments. (27)(28) This approach is applied to preterm
infants, term infants with neonatal encephalopathy or con-
genital heart disease, and all infants with malformations
requiring surgical correction. This protocol was described
by Iona Novak and colleagues; while offering some expla-
nation to parents, it also provides support at times of
maximal brain plasticity. (29) Early diagnosis may qualify
the child for additional assistance in the form of therapy
sessions, assistive technology, insurance benets, and fed-
eral assistance. (30) Parents of children with moderate to
severe CP will likely already have concerns about the devel-
opment of their child, and often providing a diagnosis helps
them move forward and acquire necessary information,
support, and services for their child.
Children with CP require ongoing, multispecialty follow-
up including developmental, neurologic, rehabilitation,
orthopedic, ophthalmology, audiology, speech, occupational,
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and physical therapies. Many authors advocate a family-
centered, holistic approach that is not merely focused on
achieving ambulation, but on maximizing overall function-
ing. (31)(32)(33) Parents and providers should aim at pro-
moting independence in daily activities rather than focusing
on learning skills, similar to children without disabilities.
This requires the liberal use of assistive devices such as
splints, walkers, and mobility devices as well as access to
switches. Among children with speech and articulation dif-
culties, the use of sign language, pictures, and augmen-
tative communication technology is essential. (32) For
children with spasticity, medical treatments such as bot-
ulinum toxin injections and intrathecal baclofen are com-
monly prescribed; surgical therapies such as selective
dorsal rhizotomy and specic orthopedic surgeries are
also used. (34) The combined goals for these interventions
are to prevent deformity, optimize motor functioning, and
promote well-being.
Children with CP face multiple comorbidities in addition
to speech and motor impairments including pain, seizures,
undernutrition, urinary incontinence, sleep and behavior-
al problems, and autism spectrum disorders. (5)(35) For
some children, these comorbidities may affect health and
social roles and may be more distressing than their motor
limitations.
It is important to remember the burdens and stresses
faced by the caregiver, usually mothers, of a child with
a chronic illness and special neurodevelopmental health
needs. (36) Providers should take into account the health
and well-being of the family and not just the child with CP.
Many new alternative therapies have been described but
not adequately studied; physicians should adopt an honest
and practical approach to helping families who are trying to
provide the best opportunities for their child with CP to
learn and be as independent as possible.
Long-term Outcomes: Risk for Additional Disabilities
CP encompasses a wide spectrum of severity, and not all
children with CP require wheelchair assistance. (37) Chil-
dren who achieve head control by 9 months of age, who
are sitting by 2 years of age, and who have suppression of
primitive reexes by 18 to 24 months of age are more likely
to achieve eventual ambulation than those who do not
achieve these milestones. (24)(37)
The type of CP and motor involvement based on the
Gross Motor Function Classication System (GMCFS) level
can help in understanding gross motor prognosis. Children
within a GMCFS level usually develop certain levels of mo-
bility, so a child at GMFCS level 1 to level 2 at age 2 years is
likely to attain upright walking and have fewer comorbidities
Vol. 17 No. 6 JUNE 2016 e327
 at a later age than a child who is at GMFCS level 5 at the same
age. (36)
In a population study of 8-year-old children with CP, 58%
were able to walk independently and 11% were able to walk
with assistance. (35) In addition, adults with CP who had
achieved independent walking before 3 years of age were
likely to maintain independent walking. (31) Many infants
with signs of mild CP at 1 year of age have normal motor
performance at 7 years of age but may continue to have
intellectual disability and seizures. (38)
The most common form of CP in premature infants
(>75%) is the spastic diplegic type affecting the lower
extremities. One-third of these infants have varying degrees
of cognitive impairment, but most are able to walk with or
without assistance, can perform independent care, and have
bowel-bladder control. Those with hemiplegic spastic CP
(most common in those with unilateral strokes, vascular
malformations, and unilateral IVH or PVL) are able to walk
by 3 years of age, but two-thirds will have a spectrum of
cognitive and learning impairment. Infants with dystonic
types of CP tend to have more speech and articulation
problems, problems with controlling movements, and
drooling and swallowing problems, but about half have
normal intelligence and achieve ambulation. Infants with
hypotonic or quadriparetic CP are less likely to achieve
ambulation, whereas infants with athetoid CP have a vari-
able outcome.
DEVELOPMENTAL COORDINATION DISORDER
Although CP is the more severe and more commonly known
motor disability, a milder form of motor disability called
developmental coordination disorder (DCD) is an important
cause of motor performance delays, and has diverse conse-
quences on childrens educational and social roles. DCD is
dened as an impairment of motor performance sufcient
to produce functional performance decits not explicable by
the childs age or intellect, or by other diagnosable neuro-
logical or psychiatric disorder.(39) The term refers to motor
disabilities that affect day-to-day functioning such as lack of
coordination, balance, dexterity, and ball skills. For example, a
child with DCD may have problems tying his shoe laces,
riding a bike, working a keyboard, or in handwriting.
Children with DCD are at risk for cognitive and academic
problems as well as behavior problems and social isolation.
Over time, they learn to avoid motor tasks that are difcult.
These motor problems can persist well into adolescence
and young adulthood, and these children are at risk for
obesity and poor cardiovascular health as well as accidents.
(40)(41)(42)(43)(44)(45) Early recognition and intervention
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are important in identifying children at risk and enrolling them
in therapies to achieve optimal functioning and avoid long-
term physical, social, and behavioral issues. (40)(46)
The reported incidence of DCD in extremely low-birth-
weight (ELBW) infants between ages 5 and 13 years is
between 5% and 50%, with most studies reporting a 30%
incidence. (29)(47)(48)(49)(50) In ELBW infants without
major motor disabilities, the incidence of DCD at 8 years of
age was 10%. (46) Incidence in normal birthweight infants
is about 2%. (46) The variation in incidence reported by
different studies is due to the wide variation in use of
diagnostic tests and different cutoff points, denition of
DCD, and coexisting behavioral conditions such as attention-
decit/hyperactivity disorder in children with DCD.
Extremely preterm and very low-birthweight infants are
at risk for DCD. ELBW male infants are at greater risk of
developing DCD than are female infants. (51) Although
IVH and PVL increase the risk for CP, they have not been
shown to independently increase the risk of DCD. Pro-
longed rupture of membranes, retinopathy of prematurity
(ROP) and postnatal steroid exposure have also shown to
be associated with risk of DCD. (52)(53)
Although there is no consensus on when DCD can be
diagnosed, most tests are able to diagnose DCD by age 5
years. (54) The most commonly used test for DCD is the
Movement Assessment Battery for Children. Children with
DCD usually do not have problems with early milestone
acquisition. For the general pediatrician, certain clues can
be elicited from the history and clinical observation. Chil-
dren with DCD may be clumsy, slow in their movements,
unable to correct motor tasks (repeatedly perform the same
task even when they are not successful), rely on visual cues,
lack uidity in their movements, and often withdraw from
physical activities and sports. (54)
Early physical therapy and education of the family can help
alleviate some motor skill problems. Children with DCD have
trouble learning new motor skills, but do better with repet-
itive, predictable skills such as bicycling or swimming. Skills
that rely on multiple sensory cues and are unpredictable, such
as football or hockey, may be difcult for them to learn. (54)
Educating families about these issues would help them set
realistic goals for their child, and help promote physical
activities that are not overwhelming for their child.
HEARING AND VISUAL IMPAIRMENT
Prevalence
Hearing and vision loss are relatively uncommon in the
general newborn population. Hearing loss accounts for
signicant disability in 0.1% to 0.3% of infants, (55) but
in those who spend more than 5 days in the NICU, the risk with known risk factors is critically important throughout
increases 10-fold to 2% to 4%. (55)(56) The global incidence childhood because subsequent screening may show hearing
of signicant visual disability and blindness in infants varies loss. (58)(59) Despite the work to identify infants with hearing
greatly. In developed countries, ROP is a leading cause of loss, of those infants diagnosed, only 61.7% were enrolled in
visual impairment and blindness. (57) The incidence of early intervention services. (64)
ROP is 0.12% and up to 15% in premature infants. (57) In
these infants, severe visual impairment is seen in 1.5% to
Impact of Timely Diagnosis
4%. (58)
Many studies have shown that early identication and
therapy can improve the long-term speech, language, cog-
At-Risk Infants
nitive, and social interactions of children with hearing loss.
Many NICU conditions contribute to the potential for
(55)(56)(59) Several large trials examining ROP outcomes
hearing loss, including any care for more than 5 days such as
have shown that timely diagnosis and treatment either with
extracorporeal membrane oxygenation, craniofacial anoma-
laser or bevacizumab improve disease progression and ulti-
lies, assisted ventilation, in utero or postnatal infection,
mately preserve healthy vision. (65)(66)
exposure to ototoxic medications such as loop diuretics, or
hyperbilirubinemia requiring exchange transfusion. (55)(59)
In addition, any newborn whose caregiver has a concern CONCLUSION
regarding hearing, speech, language, developmental delay, or
The major role of neonatal follow-up has been to coordi-
a family history of hearing loss is at higher risk. (55)(59) The
nate the support that families require for infants who
main risk factor for visual impairment in developed countries
present with the signs and symptoms of CP and neuro-
is ROP and is driven largely by oxygen exposure during the
sensory disability in the rst 2 years after birth. However,
NICU course. (60)(61) Infants exposed to intrauterine infec-
there is much interest in applying evidence-based early
tions and congenital cataracts are also at risk for visual
interventions to promote plasticity and have a positive
impairment.
impact on child functioning and family well-being. This
requires a combination of neurodevelopmental surveil-
Identication of Hearing or Vision Loss
lance; interdisciplinary collaboration with physical, occupa-
Screening at birth can identify many patients, but the risk of
tional, and speech therapists; and collaborative relationships
developing hearing loss continues throughout childhood.
with audiologists, otolaryngologists, and ophthalmologists.
Infants should be screened before age 3 months and age-
In this way, we can also better understand our need for
appropriate intervention should be in place no later than age
improving science, ongoing care, community support, and
6 months. (59) Any child who has a risk factor for hearing
advocacy.
loss, regardless of newborn screening results, should be
regularly screened with at least 1 audiology assessment by
age 24 to 30 months. (55)(59)(62) ROP screening should be
conducted for all infants born at a gestational age of less than American Board of Pediatrics
or equal to 30 weeks or birthweight less than or equal to NeonatalPerinatal Content
1,500 g or other infants of more than 30 weeks gestation Specications
with an unstable clinical course. The rst examination
Know the neonatal conditions that are associated with vision loss
should be performed at a chronologic age of 4 to 6 weeks in preterm and full-term infants.
or at 31 weeks corrected gestational age. (63) Subsequent Know the evolution of neurodevelopmental impairments during
examinations are repeated based on the clinical ndings. development and the difference between transient and
permanent impairments in NICU graduates (eg, developmental
Infants Who Are Not Identied delay vs. intellectual disability; tone abnormalities vs. cerebral
The average age of detection of signicant hearing loss is palsy).

14 months. (55) With universal screening, the focus has Know the rationale for early intervention programs for infants at
risk for cognitive and behavioral problems.
shifted to infants who may pass an initial otoacoustic
Know the incidence, causes, risk factors, and approaches to
emissions test but have an abnormal auditory brainstem-
evaluation and management of acquired hearing loss in the
evoked response. These infants with auditory neuropathy
neonate.
are typically smaller and more premature than those with
sensorineural hearing loss. (62) Follow-up of all infants

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Vol. 17 No. 6 JUNE 2016 e331
 NeoReviews Quiz
There are two ways to access the journal CME quizzes:
1. Individual CME quizzes are available via a handy blue CME link in the Table of Contents of any issue.
2. To access all CME articles, click Journal CME from Gateways orange main menu or go directly to: http://www.
aappublications.org/content/journal-cme.

1. An infant born at 28 weeks gestational age is now 24 months old and being evaluated at NOTE: Learners can take
the high-risk infant follow-up clinic. There is concern for cerebral palsy. Which of the NeoReviews quizzes and
following statements regarding preterm birth and cerebral palsy is correct? claim credit online only
A. At this age, cerebral palsy is often transient and about 50% of cases will resolve by at: http://Neoreviews.org.
school age.
B. Cerebral palsy is a clinical description and lacks specic pathologic or radiographic To successfully complete
features, with some infants with cerebral palsy having a normal brain magnetic 2016 NeoReviews articles
resonance imaging scan. for AMA PRA Category 1
C. The dening characteristic of cerebral palsy is progressive brain injury. CreditTM, learners must
D. Prematurity is the main risk factor in 75% of cases of cerebral palsy. demonstrate a minimum
E. The prevalence of cerebral palsy in infants born at 28 weeks gestational age is 15% performance level of 60%
to 20%. or higher on this
2. An 18-month-old infant is being evaluated for possible cerebral palsy. Which of the assessment, which
following is a risk factor for cerebral palsy? measures achievement of
A. Female gender. the educational purpose
B. Absence of sepsis during initial hospitalization. and/or objectives of this
C. White race (compared with Africa American race). activity. If you score less
D. Intrauterine growth restriction. than 60% on the
E. Hyperthyroidism. assessment, you will be
given additional
3. An 8 year old with cerebral palsy requires a wheelchair. She attends mainstream class in
opportunities to answer
school with individualized assistance from an aide. Which of the following statements
questions until an overall
regarding the prognosis of cerebral palsy in childhood is correct?
60% or greater score is
A. Children who achieve head control by 9 months of age and who are sitting by 2 achieved.
years of age, and have suppression of primitive reexes by 18 to 24 months of age
are more likely to achieve eventual ambulation than those who do not achieve
those milestones. This journal-based CME
B. Children who have a Gross Motor Function Classication System level of 5 have the activity is available
highest likelihood of achieving more independence and abilities in performing through Dec. 31, 2018,
daily activities of life. however, credit will be
C. Among 8-year-old children with cerebral palsy, 90% are not yet ambulating recorded in the year in
independently. which the learner
D. The most common form of cerebral palsy in preterm infants is double hemiplegia. completes the quiz.
E. Almost all infants with dystonic types of cerebral palsy have normal intelligence but
very few (<10%) will achieve ambulation.
4. A 5-year-old child who was born at 30 weeks gestational age is being evaluated for lack of
coordination and balance. There is concern for developmental coordination disorder.
Which of the following statements regarding developmental coordination disorder is
correct?
A. The disorder is dened as an impairment of motor performance that is noticeable
on physical examination, but insufcient to produce functional performance
decits.
B. The disorder is not associated with any risk of cognitive or behavioral problems.
C. The disorder is characterized primarily by difculties in very ne motor skills such as
handwriting or typing, but with no difculties in gross motor skills such as riding a
bicycle.
D. Children with this disorder usually do not have problems with early milestone
acquisition.

e332 NeoReviews
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 E. A hallmark of diagnosis is that almost all patients with the disorder had either grade
2 to grade 4 intraventricular hemorrhage or periventricular leukomalacia during
the neonatal period.
5. An 18-month-old infant has no words and is being evaluated for hearing loss. Which of the
following statements correctly describes risk of hearing loss in newborns?
A. Screening soon after birth should identify all cases of childhood hearing loss.
B. Care in the NICU for more than 5 days, extracorporeal membrane oxygenation,
craniofacial anomalies, assisted ventilation, and hyperbilirubinemia requiring
exchange transfusion are some factors that increase risk of hearing loss.
C. In a child who has a risk factor for hearing loss, but normal newborn hearing
screening, the next audiology assessment should occur right before starting
kindergarten.
D. The average age of detection of hearing loss is 20 months of age.
E. Although early intervention programs make sense, studies have not yet shown
signicant positive impact of early identication and therapy in children with
hearing loss.

Parent Resources from the AAP at HealthyChildren.org

https://www.healthychildren.org/English/health-issues/conditions/developmental-disabilities/Pages/Cerebral-Palsy.aspx
Spanish: https://www.healthychildren.org/spanish/health-issues/conditions/developmental-disabilities/paginas/cerebral-palsy.aspx
https://www.healthychildren.org/English/health-issues/conditions/eyes/Pages/Warning-Signs-of-Vison-Problems-in-Children.aspx
(English only)

Vol. 17 No. 6 JUNE 2016 e333

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 Cerebral Palsy, Developmental Coordination Disorder, Visual and Hearing
Impairments in Infants Born Preterm
Krishna Acharya, Matthew Pellerite, Joanne Lagatta, Bree Andrews and Michael E.
Msall
NeoReviews 2016;17;e325
DOI: 10.1542/neo.17-6-e325

Updated Information & including high resolution figures, can be found at:
Services http://neoreviews.aappublications.org/content/17/6/e325
References This article cites 64 articles, 19 of which you can access for free at:
http://neoreviews.aappublications.org/content/17/6/e325#BIBL
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 Cerebral Palsy, Developmental Coordination Disorder, Visual and Hearing
Impairments in Infants Born Preterm
Krishna Acharya, Matthew Pellerite, Joanne Lagatta, Bree Andrews and Michael E.
Msall
NeoReviews 2016;17;e325
DOI: 10.1542/neo.17-6-e325

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://neoreviews.aappublications.org/content/17/6/e325

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