1. Predicting Developmental Delays in Preterm Infants Using MRI

2. Navigation
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3. Table of Contents Research Results Conclusions References
Infants at Risk
Research
Developmental Delays
Variables
Assessments
Types of Delays
Results
Current Method
MRI
Study One
Basics
Study Two
Sequences
Conclusions
Examples
References
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4. Objectives
Identify infants at risk and discuss potential developmental delays
Learn about current methods in imaging used to determine possible future delays
Explore how MRI works and the types of scans utilized in both studies
Differentiate between the methods and scoring systems of both studies
Analyze the research data and draw conclusions

5. Infants at Risk
Gestational age is a measurement, beginning on the first day of a woman’s last menstrual period, and is used to determine the due date
It is generally confirmed with ultrasound measurements taken around six weeks1
A full term pregnancy is weeks gestation
Any pregnancy 37 weeks or less is premature or preterm; infants born between weeks are late-preterm; infants that do not make it to 32 weeks are very preterm2
Infants born within these categories, as well as those born at a very low birth weight (VLBW) of <1500g, are likely to face future developmental delays3
Previously, “children born at 34 weeks’ gestation and later were not closely researched because they were never that sick after being born… and they received very little follow-up.”4
Since then, researchers have noticed an increase of infants born after 32 weeks but before 37 weeks that have gone on to experience cognitive and developmental delays at higher rates than their full term peers4

6. Developmental Delays
Children may experience one or several delays involving gross or fine motor, language, social, or thinking skills5
“A developmental delay is when your child does not reach their developmental milestones at the expected times”
It is imperative to a child’s future progress that it is diagnosed early on
“Recent estimates in the United States show that one in six or about 15% of children … have one or more developmental disabilities.”6
Some proactive measures would be to enroll their child in physical, occupational, or speech therapy 7
A early diagnosis would allow physicians and parents to better prepare for learning and developmental challenges in their children’s future
In order to understand the significance of early intervention with developmental delays, it is important to have some knowledge of various types of delays and their long term effects

7. Types of Delays
Cerebral palsy (CP) is one of the main delays that has been observed in studies performed for predicting future delays
“CP is a group of disorders that affect a person’s ability to move and maintain balance and posture. CP is the most common motor disability in childhood.”6
CP may also be associated with vision and or hearing impairments
Another deficit researched was a delay in motor function, both fine and gross motor.
“Fine motor skills are those that require a high degree of control and precision in small muscles”8
“Gross motor skills use large muscles in the body and include broader movements such as walking and jumping”8
Although only select developmental delays were researched in the MRI studies, there are numerous areas in which a preterm infant could experience deficits

8. Current Methods
Currently, the most widely used and accepted method of neuroimaging for preterm infants is cranial ultrasound (CUS)9
Ultrasound (US) utilizes sound waves that travel through soft tissue and fluids, but echoes off denser surfaces, to create an image1
This can check for abnormalities in the brain, hydrocephalus, and periventricular leukomalacia, a form of white-matter brain injury1
Procedures and results can vary depending on different protocols, the skill level of a sonographer, and the timing of the CUS9
Medical professionals have been conducting studies to determine if magnetic resonance imaging (MRI) of the brain would be more informative than a CUS in determining developmental delays in preterm infants

9. MRI Basics
Magnetic Resonance Imaging (MRI) is a type of diagnostic imaging that utilizes a magnetic field, radio waves, and computers to produce a highly detailed image
Field strength of MRI scanners, measured in Tesla, usually vary between 0.5 and 3 Tesla10
The basis of image formation is aligning the hydrogen nuclei, from water molecules in your body, into a magnetic field
Hydrogen protons act like a bar magnet; when a radio frequency pulse is produced and energy is added to the magnetic field, the hydrogen protons change their orientation to a uniform alignment. When the radio frequency pulse is turned off the hydrogen protons relax and return to their original orientation, emitting a signal that is received by a coil
Different body tissues have a range of relaxation rates due to varying hydrogen content
A scanner is able to distinguish between the various signals emitted11
These variances provide exceptional detail for viewing structures such as joints, cartilage, muscles, bones, and fluid10

10. MRI Sequences
In order to emphasize different tissues or abnormalities, such as fat versus fluid, there are several radio frequencies that can be utilized
There are several ways, or sequences used, to measure various tissue types
The first, T1-weighted, is the amount of time it takes for the magnetic vector to return to its resting state
On T1 images tissues appear bright or white, and fluid appears dark10
Another sequence, T2- weighted, is the measure of time needed for the axial spin of the proton to return to its resting state
T2-weighted images can be considered opposite of T1, as T2 images portray fluid as bright10
Both types of radio frequency pulses are utilized to observe the normalcy, or lack thereof, in ventricular size, white matter volume, myelination of the internal capsule, and other anatomical markers10

11. MRI Examples
A common way of grading deformities is by stating whether they show none, mild, moderate, or severe abnormalities
Figure 1 shows coronal slices of T2 images in section A and T1 images in section B
Each slice shows the four grades of white matter abnormality (WMA)
Section C shows axial T2 images of what normal gray matter should look like in infants
Section D demonstrates smooth gyri patterns that are observed in infants with gray matter abnormalities11
Figure 1

12. Research Variables
Numerous studies have been performed using MRI to look for abnormalities at term equivalent and again around two years of age; the main focus will be on two studies that used both MRI and CUS for comparison
Study one12
167 preterm infants over a period of three years, born at 30 weeks or less
Neonates were, “fed, wrapped, and placed, unsedated, in a Vac Fix beanbag to keep the infant still”
1.5 T General Electric (GE) Signa System was used
Study two9
480 infants born throughout a four year period
“neonatal brain MRIs could be obtained without the use of sedation… MRI was obtained at 35 to 42 weeks’ [post menstrual age] PMA, ideally within 7 days of the late CUS”
1.5 T system was a minimum requirement

13. Research Assessments Study one12
All scans were scored by one of the authors and by a pediatric neuroradiologist (Christchurch) or neonatologist (Melbourne)
Raters were unaware of infants’ history and used a scoring system comprised of eight 3-points scales
Within two years of the MRI, children received a comprehensive assessment using the Bayley Scales of Infant Development (BSID-II) and a standardized pediatric neurologic evaluation
The predictions of the MRI findings were compared to each neonate’s original assessments and CUS results
Study two9
All brain MRIs were reviewed by Dr. Barnes, using a central reader form
Dr. Barnes was unaware of and not privy to any information regarding the infants; scoring according to a widely used system
Around 18-22months from their term equivalent, children underwent both a neurological and comprehensive assessment, using the Bayley Scales of Infant Development (BSID-III)
The results were compared to the initial CUS and MRI, as well as a report from the child’s primary caregiver
Research Assessments

14. Results of Study One
Of the original 167 infants, three children were excluded; one child that was blind and two children that had limited available data for review
Upon interpretation, a positive correlation was found between increased WMA at term equivalent and decreased cognitive and psychomotor performances at age two
The children were also found to have a greater risk of severe motor delay, severe cognitive delay, neurosensory impairment and cerebral palsy
As shown in Table 2, infants that had more severe WMA had a greater number of developmental delays or impairments than infants with none or mild WMA12

15. Outcome at 18–22 mo Corrected Age
Results of Study Two
Of the original 480 participants, the final results were narrowed down to 445 participants due to 15 infants dying and 20 infants not partaking in the follow up
This study utilized a similar scale, as the first study, for evaluating the severity of WMA
Table 3 shows a similar trend in results to that of the research in previous years
Infants with the most severe white matter abnormality also had the lowest mean cognitive scores and most significant rates of motor impairment, neurodevelopmental impairment or death9
Outcome at 18–22 mo Corrected Age
Severity of WMA
Normal, n = 98
Mild, n = 261
Moderate, n= 68
Severe, n= 18 P
Cognitive score, mean ± SD
93.5 (14.0)
92.6 (13.1)
89.9 (15.3)
77.7 (14.5)
<.0001
Cognitive score <70
4/98 (4.1)
11/258 (4.3)
7/67 (10.5)
4/18 (22.2)
.011
Cognitive score <85
20/98 (20.4)
47/258 (18.2)
20/67 (29.9)
11/18 (61.1)
.0001
Any CP
2/98 (2.0)
14/261 (5.4)
4/68 (5.9)
Moderate to severe CP
0/98
3/261 (1.2)
1/68 (1.5)
9/18 (50.0)
NDI
16/258 (6.2)
Significant gross motor impairment
1/98 (1.0)
5/261 (1.9)
10/18 (55.6)
Unimpaired/mildly impaired
69/98 (70.4)
176/258 (68.2)
40/67 (59.7)
3/18 (16.7)
NDI or death
25/267 (9.4)
11/71 (15.5)
13/20 (65.0)

16. Conclusions
Even though CUS is the current standard for neuroimaging in preterm infants, it has been proven that MRI could greatly benefit the diagnosis of WMA and potential future impairments
Whether MRI is used independently or along with CUS, the benefits of early prediction are undeniable
A more accurate diagnosis using MRI would allow physicians to recommend early intervention such as physical, occupational, or speech therapy
Parents would be able to receive counseling, learn strategies, and overall be better prepared
With interventions, children would have a much greater likelihood of overcoming, or at least better management of, any impairment
The results that have been proven in studies thus far, point to potential need to reevaluate the current neuroimaging procedures for preterm infants

17. References
1Debra Rose Wilson C. Ultrasound scans: How do they work?. Medical News Today. Published Accessed March 21, Calculating Conception. American Pregnancy Association. due-date/. Published March 28, Accessed December 1, Caesar R, Boyd RN, Colditz P, et al. Early prediction of typical outcome and mild developmental delay for prioritization of service delivery for very preterm and very low birthweight infants: a study protocol. BMJ Open 2016;6:e doi: /bmjopen Davey M. Developmental delay in 'moderate to late' preterm babies, study finds. The Guardian. Published February 6, Accessed November 15, Boyse K. University of Michigan Health System. CS Mott Children's Hospital | Michigan Medicine. Published February Accessed November 14, Facts About Developmental Disabilities | CDC. Centers for Disease Control and Prevention. Published April 17, Accessed November 7, Miller B. MRI scans in premature infants can predict future developmental delays. in-premature-infants-can-predict-future-developmental-delays/. Accessed August 16, Mauro T. What Are Fine and Gross Motor Skills? Verywell Family Published September 25, Accessed November 6, 2018.

18. 9 Hintz SR, Barnes PD, Bulas D, et al
9 Hintz SR, Barnes PD, Bulas D, et al. Neuroimaging and Neurodevelopmental Outcome in Extremely Preterm Infants. Pediatrics. Published January 1, Accessed November 7, Lewis T. What is an MRI (Magnetic Resonance Imaging)? LiveScience. mri.html. Published August 11, Accessed November 6, Berger A, ed. Magnetic Resonance Imaging. National Center for Biotechnology Information. Published January 5, Accessed December 7, Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants | NEJM. New England Journal of Medicine. Published August 17, Accessed November 7, Image 1: Griffiths A. MRI Scan; Accessed March 15, Image 2: Hydrogen Protons; =X&ved=0ahUKEwjx4KDKx57hAhVo04MKHUtuAvoQ_AUIDigB&biw=1536&bih=722#imgdii=9pFjSKFC6Jj dAM:&imgrc=LATUiaNr3dqHPM:. Accessed March 19, Figure 1: Representative MRI Scans of Children in the Study.; Accessed November 7, Table 2: Neurodevelopmental Outcomes at a Corrected Age of Two Years.; Accessed November 7, Table 3: Severity of White Matter Abnormality.; Accessed November 7, 2018.