Brain development undergoes significant changes during the third trimester of pregnancy between 32 and 40 weeks gestation. Studies have found reductions in total brain volume, white matter volume, and grey matter volume correlated with lower gestational age and birth weight in preterm infants compared to full-term infants. Specific brain regions like the temporal lobe, corpus callosum, thalamus, and occipital-temporal gyrus experience delays in gyrification and myelination if an infant is born preterm during this critical period of rapid brain growth and development in the third trimester.

1. Relationship between
Brain Volume
Maturation and
Gestational Age
ozella.brundidge@gmail.com 4/8/2017
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2. “Being Born Just a Few Weeks too Early, between 32 and 36 Completed Weeks of Gestation, May have More Effect on
Brain Growth and Maturation than Previously Appreciated.”
“Being Born Just a Few Weeks too
Early, between 32 and 36 Completed
Weeks of Gestation, May have More
Effect on Brain Growth and Maturation
than Previously Appreciated.”
(Walsh, Doyle, Anderson, Lee, & Cheong, 2014, p. 232; Dubois, Benders, Cachia, Lazeyras, Ha-Vinh, Leuchter,
Sizonenko, et al., 2008)
2
26.7 Weeks
30.0 Weeks
35.7 Weeks
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3. White Matter Volume and Concentration Reductions in
Adolescents with History of Very Preterm Birth
•
3
Researchers found a significant correlation
between white matter (WM) decreases and both
gestational age (GA) and gestational weight
(GW) in various brain regions: The lower the
GA and GW, the lower the WM integrity.
(Gimenez, Junque, Narberhaus, Bargalo, Botet, Mercader, 2006) ozella.brundidge@gmail.com 4/8/2017

4. Preterm Birth has a Significant Impact on Grey
Matter and White Matter Volume, the Temporal
Lobe being the Most Affected RegionThe Right Temporal Lobe is the
Most Affected Region in Preterm
children.
(Soria-Pastor, Padilla, Zubiaurre-Elorza, Ibarretxe-Bilbao, Botet, Costas-Moragas, Falcon, et al., 2009)
Soria-Pastor and colleagues (2009) found correlations between WISC-IV full-scale IQ scores of 9-year old
preterms (30-34 GA) and grey matter volume involving the middle temporal gyrus (BA 21) and the postcentral
parietal gyrus (BA 1, 2, 3, and 7)
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5. Allometry is the Study of Relationships between Body Size to
Shape, Anatomy, Physiology and Behaviour
Human brain growth obeys an
allometric scaling relation that is
disrupted by preterm birth in a
dose-dependent, sexually dimorphic
fashion that directly parallels the
incidence of neurodevelopmental
impairments in preterm infants.
5
(Kallepou, et al., 2006; Shingleton, 2010) ozella.brundidge@gmail.com 4/8/2017

6. Third Trimester Cortical and Cerebral Growth
6Kapellou, et al., 2006
Figure 3
Gyrification leads to
accelerated growth
in surface area.
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7. Serial MRI of Brain Growth in a
Normal Female Preterm Infant
• Gestational age 25 weeks
• Birth weight 710 grams
• MR images obtained between 26 and 39
weeks gestational age
• Images show slices through the brain at the
mid-ventricular level and at the level of the
centrum semiovale from six of the eight
• There is a linear relationship that indicates
power law scaling of cortical surface area
relative to cerebral volume in this individual
7
ozella.brundidge@gmail.com 4/8/2017(Kapellou, Counsell, Kennea, Dyet, Saeed, Stark, Maalouf, et al., 2006)

8. Brain Growth and Development of 25 Week old
Preterm Girl between 26 and 39 weeks Old
8
(Kapellou, Counsell, Kennea, Dyet, Saeed, Stark, Maalouf, et al., 2006; Poulsen, Wolke, Kurinczuk, Boyle, Field,
Alfirevic, & Quigley, 2013)
Figure 2. Serial MR Imaging of Brain Growth in a Normal Female Preterm Infant
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9. larger volumes for the whole brain and various segmented brain tissues were
associated with better development in cognitive, language, and to a lesser extent,
motor domains.
9
Cognitive
Domain
Language
Domain
Motor
Domain
Larger Volumes for the Whole Brain and Various Segmented
Brain Tissues were Associated with Better Development in…
(to a lesser extent)
Their mean scores on Bayley Scales of Infant and Toddler Development, 3rd Ed. ranged between 99 and 104 each
domain. Although Anderson and colleagues (2010) raised concerns about the Bayley-III underestimating
developmental delay in the Australian population.
Brain Volume of Moderate to Late Preterm Born 2-Year Old
Toddlers may be an Important Marker for Neurodevelopment
(Cheong, et al., 2016)
MPT (32-33 weeks) LPT (34-36)
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10. Developmental Changes occur in the Fetal
Brain during the 3rd Trimester of Gestation3rd Trimester
Developmental Changes
in the Fetal Brain
Sulcation Organization
Grey Matter White Matter
Maturation
changes in
(Aeby, et al, 2012, Fig. 1 in part; Dubois, Benders, Cachia, Lazeyras,
Ha-Vinh, Leuchter, Sizonenko, et al., 2008, Fig. 2 in part)
Gyrification
undergo cortical
26.7 weeks
30.0 weeks
35.7 weeks
(2008, Fig. 2)
(2012, Fig. 1)
10
Myelination
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11. 11
Cerebral
White Matter
Corpus
Callosum
Deep Nuclear
Gray Matter
Cerebellum
(Walsh, Doyle, Anderson, Lee, Cheong, 2014, fig. 2; Cheong, et al., 2016)
Using a
2-Dimensional “Linear Metrics”
Reductions
• Diameter of parietal lobes bilaterally
• Thalami
• Basal ganglia
Moderate and Late Preterm Infants at Term-Equivalent Age had Smaller
Brain Matter Compared with Term Controls
(a) brain fronto-occipital distance (FOD)
(b) corpus callosum (CC), anteroposterior
distance (AP), genu, midbody (MB), and
splenium (SP) measurements.
ozella.brundidge@gmail.com 4/8/2017
Moderate and Late Preterm Infants at Term-Equivalent Age
had Smaller Brain Matter Compared with Term Controls

12. Preterms Show Global and Regional Reductions in
Grey Matter and White Matter Volumes
MRIs - Macrostructures
• Myelinated white matter
• Significant reductions in left
temporal regions
• Thinner corpus callosum
• Lesions
DTIs - Microstructures
• FA of Axonal coherence
• Myelination
• Microstructure connectivity
(Norsarti, et al., 2008 (<33 weeks); Rogers, et al., 2014 (34-36); Soria-Pastor, et al., 2009 (30-34); Woodward, et al., 2005 (≤32 weeks);
Nagy, et al., 2009 in Lubsen, et al., 2011; Aeby, et al., 2012)
12ozella.brundidge@gmail.com 4/8/2017

13. Given that only 60% of the human brain volume is present at 32 weeks gestation,22 hypoxia,
hypotension, and several noxious stimuli in the extrauterine environment might disrupt
various maturational processes, including increased neuronal connectivity, dendritic arborization,
formation of synaptic junctions, and maturation of neurochemical and enzymatic
processes.2,23
13
Only 60% of the brain volume is present
between 32-35 weeks gestation. Hypoxia,
hypotension, and several noxious events in
the extrauterine environment might disrupt
various maturational processes…
Neuronal
Connectivity
Dendritic
Arborization
Formation of
Synaptic
Junctions
Maturation of
Neurochemical
and Enzymatic
Processes
(Cheong, et al., 2016; Kerstjens, et al., 2011; van Baar, et al., 2009 in
2011; Kinney, et al., 2006 in 2011; Billiards, et al., 2006 in 2011)
Fewer gyri, sulci, dendrites,
astrocytes, & microglia
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14. The Preterm Brain is 5-6% Smaller than Full-Term
Control Children at School Age
Imaging studies have found a
relationship between the corpus
callosum (CC) size and neuro-
psychological outcomes of very
preterm born children. The corpus callosum size positively and
significantly correlated with total white
matter volume in both preterm individuals
14
(Nosarti et al., 2002; Nosarti, et al., 2004; Peterson
et al., 2000; Constable, Vohr, Scheinost, Benjamin,
Fulbright, Lacadie, Schneider, et al., 2013)
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15. Corpus Callosum Reduction in the Language Impaired Preterm Adolescents
(mean GA 27 weeks; mean age 16 years)
15
(Northam, Liegeois, Tournier, Croft, Johns, Chong, Wyatt, et al., 2012)
***pronounced
reduction in
segment V
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16. The Posterior Part of the Thalamus is Connected to the Posterior
Parts of the Cerebral Cortex
• Middle Geniculate Body
connects the thalamus to the
auditory cortex.
• The thalamus nuclei is also
connected to:
 Motor cortex
 Prefrontal cortex
Increasing prematurity is related to volume reduction, neuronal loss, gliosis, and axonal
abnormality in the thalamus (Ball, et al., 2012; Volpe, 2009)
16
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17. There is a Significant Effect of Prematurity on Thalamic Volume
which is Related to Specific Abnormalities in Connected Brain Structures
Thalamic volume is also related to both the microstructure of the thalamic radiations, carrying projection
fibers to the cortex, and the volume of the cortex itself (Ball, et al., 2012)
17
Orbitofrontal Lobe
Hippocampus
Posterior
Cingulate Cortex
Centrum
Semiovale
Thalamus
Anterior Temporal Lobes
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18. Cingulate Gyrus Mediates CommunicationCingulate Gyrus
Lies directly above
Corpus Callosum
(Bethopedia, 2012; Jensen, 2005)
Mediates
Communication
between the
Cortex
(temporal, frontal,
parietal, occipital
lobes)
Midbrain
structures
(hippocampus,
thalamus)
&
Involved with:
• Emotions,
• Decision making,
and
• Right-wrong
behaviors
Help to shift
from
one mind-body
state to another
18
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19. Right Lateral Occipitotemporal Gyrus
Face
Processing
FA decrease between 34
and 39 weeks followed
by FA increase from 40
weeks to 43 weeks
The Right Lateral Occipitotemporal Gyrus Experiences Major
Microstructural and Maturational Changes Gestational Week 40
Both the Fusiform Face and
the Occipital Face areas
Comprised of
Sensitive to Face
Stimuli
(Aeby, et al., 2012; Gauthier et al., 1999 in 2012; Kanwisher, 2000 in 2012; Hein & Knight, 2008 in 2012; Turk-
Browne et al., 2010 in 2012; Atkinson & Adolphs, 2011 in 2012)
Exhibit Greater Activation to
Face Stimuli than:
Scrambled
Stimuli
Various
Objects
Experiences
[Fractional Anisotropy (FA)]
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20. Brain Maturation: Early Cortical Folding Process during
the 3rd Trimester is Dependent on Gestational Age
(Dubois, Benders, Cachia, Lazeyras, Leuchter, Sizonenko, et al., 2007)
20
CorticalFolding:CreationofGyriandSulci
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21. During the Last Trimester the Fetus Cerebral Cortex
becomes Greatly and Quickly Gyrified
Each fetus’s hemisphere was already asymmetric at the level of Heschl's gyrus (part of the Auditory
center), planum temporale (auditory mental lexicon) and at the superior temporal sulcus (STS) (language
processing) (Dubois, Benders, Cachia, Lazeyras, Leuchter, Sizonenko, Borradori-Tolsa, et al., 2010)
Fetus #1 #2 #3 #4
Fig 6 in part
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22. Moderate and Late Preterm (MLPT) Infants at Term-Equivalent
22
Gyral maturation is delayed in the MLPT
group. Myelination of the Posterior Limb
of the Internal Capsule is also
less developed.
(Walsh, Doyle, Anderson, Lee, Cheong, 2014; Cheong, Thompson, Spittle,
Potter, Walsh, Burnette, Lee, Chen, et al., 2016, figure 1)
MLPT: 32 - 36 weeks and 6 days
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23. Early-Term (37-38 weeks gestation) Infants are
At-Risk of having Underdeveloped Brain Matter
23
(Kinney, 2006)
Fetal Brains Experience a 5-Fold
Increase in White Matter Volume
between 35 and 41 Weeks of
Gestation
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24. End of
Relationship between
Brain Volume
Maturation and
Gestational Age
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