Fetal brain development is characterized by neurogenesis, gliogenesis, and the growth of axons and synaptic connections, particularly during the third trimester. Key processes, including myelination and neuronal connectivity, continue into early adulthood and are critical for cognitive development, with growth of gray and white matter peaking before term. Premature birth can disrupt this critical growth phase, leading to long-term neurological deficits such as reduced gray matter density and impaired cognitive functions.

1. Fetal Brain Development and Nerve Cell Functions
Myelination of axons and neuronal connectivity begin during the third trimester of fetal development
and continues until early adulthood. It is thought to be important for the development of cognitive
functions throughout childhood (Nagy, Westerberg, & Klingberg, 2004; Mento & Bisiacchi, 2012).
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American Academy of Child & Adolescent Psychiatry, 2017
Ozella Brundidge, 4/6/2017

2. Brain Development during the 2nd & 3rd Trimesters is Mostly Characterized by:
 Neurogenesis – nerve cells generated from neuronal stem cells.
 Gliogenesis – glia cells generated from multipotent stem cells.
(astrocytes, microglia, and oligodendrocytes)
 Axonal ingrowth – elongation of axons
 Elaboration of synaptic connections.
(Dreamstime, 2015; Lubsen, et al., 2011; Narberhaus, et al., 2009; Scafidi, et al., 2009) 2

3. Cortical Surface Area and Cerebral Volume Grows Dramatically
during the Last Six Weeks of Pregnancy
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(Poulsen, et al., 2013; Cheong, 2016, figure 1)
35% of brain growth
occurs between 34
weeks and 40 weeks
gestation
Figure 3. Cortical Surface Area and Cerebral Volume of
Preterm Infants

4. Fetal Brain Growth at 34 Weeks Gestation is 65% of Full-Term Weight
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• Brain weight at different ages from 20 to 40
gestational weeks is illustrated at each
gestational age as a percent of term brain weight.
• At 34 gestational weeks, the overall brain weight
is 65% of term weight. Arrow highlights brain
weight at 34 weeks’ gestation.
(Jain, 2008; Kinney,2006 in 2008)
The percent brain weights were based on the data of Guihard-Costa and Larroche (1990).

5. (Center for Disease Control, 2015; Nuclear Medical Inc., 2013; Kinney, 2006; Volpe, 2006)
Birth prior to 40 weeks
gestation Interrupts the Most
Active Period of Growth for
the Grey Matter in the Brain.
5-Fold Increase in
White Matter Volume
during Last
6 Weeks of Gestation.
Fetal White and Grayer Matter Volume Increase
Dramatically at the End of the Third Trimester

6. The Immaturity of the Laminar Position and Dendritic Arborization of Neurons
in the Cerebral Cortex in the Late Preterm Infant
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(Kinney, 2009, Figure 2)
The cerebrum
is very thin at
20 weeks.

7. Premature Birth and Low Birth Weight Alter Brain Structures
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n=137 participants
Age 13-22 years (Spencer et al., 2008 in Park, et al., 2014)
A recent MRI study of Adolescents and Young Adults
revealed that Prematurity and Low Birth Weight are
Associated with Reduced Gray Matter Density Bilaterally in
the Temporal Lobe and Cerebellum.

8. Rapid growth phase during the last trimester may cause the immature brain to be susceptible for
injury, leading to impaired growth of cerebral cortical gray matter and myelination of white
matter, disturbed development of white matter microstructure
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(Baschat, 2011 in Reveillon, et al., 2013; Huppi, et al., 2001 in Jiang, Ping, & Wilkinson, 2012; American Academy of
Child & Adolescent Psychiatry, February 2017)
…impaired growth of cerebral
cortical gray matter
…impaired myelination of
white matter
…disturbed development of
white matter microstructure
The Frontal Lobe Function is Especially Vulnerable to Fetal
Nutrient Deficiency in the Third Trimester
Rapid Growth Phase During the Last
Trimester may Cause the Immature
Brain to be Susceptible for Injury
AACAP, 2017

9. Nerve Cell Structure, Function and Myelination
9(Dreamstime, 2015)

10. Structure of a Typical Neuron
Dendrites
Cell Body
Nucleus
Axon
Nucleus of
Schwann Cell
Node of Ranvier
(Wikipedia: The Free Encyclopedia, 15 December 2016)

11. Difference between Diffused White Matter and Neurons
Diffused white matter consists of
microglia, oliogodendrocytes, and astrocytes
Neurons are made of three parts
1. Cell body – contains biological
components of neuron
2. Dendrites – receive information from
axons of other neurons
3. Axons – sends information to other
neurons(Dreamstime, 2015; Jensen, 2005, 2008)
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12. Diffused White Matter is Involved with Myelination, Cytostructural
Support, and Possibly has its own Communication Network*
(Dreamstime, 2015; Lubsen, Vohr, Myers, Hampson, Lacadie, Schneider, Katz, et al., 2011)
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Diffuse white matter injury is the major
cause of neurodevelopmental conditions
experienced by some preterm born children.
The three types of diffuse white matter are:
1. Oligodendrocyte
2. Microglia
3. Astrocyte

13. Oligodendrocytes loss may lead to temporal (timing)
dispersion of the neural impulse released during
reading tasks, which would desynchronize the neural
transmission of information to the frontal lobes and
spread out the activation over time.
(Frye, et al., 2009; Back et al., 2007 in 2009; Khwaja and Volpe, 2008 in 2009; Volpe, 2009; Dreamstime, 2015; Haynes,
et al., 2005 in 2009; Rakic, et al., 2000 in 2009; Rezaie, 2002 in 2009; Hamilton & Rome, 1994 in 2009)
Premyelinating Oligodendrocytes Loss
Underlies White Matter Injury in Preterms
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Microglia becomes prominent in the forebrain at 16-
22 weeks of gestation. The key roles during brain
development involve vascularisation, axonal
development, myelination, and apoptosis.

14. Neurons and Glia Cells
Neurons
Glia Cells
Both
Release
transmitters*
Have long-range
signaling
Can enwrap synaptic
terminals
Are connected
by gap junctions
(Jensen, 2005; Dreamstime, 2015)
Neurons:
• Dendrites receive
stimulation (information)
• Communicate with other
cells
• Create a network by nerve
impulses along their axons
Glia cells:
• Carry nutrients
• Speed repair
• Provide myelin for axons
• Support blood-brain barrier
• May form their own
communication network
• Involved in neurogenesis
*Neurotransmitters are the brain’s chemical messengers.
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Integrate
neural output

15. Myelin is an Essential Protein for Brain Development
 Myelin is a fatty white substance that coats, supports, and
insulates axons.
 It increases efficiency by allowing electrical impulses to
travel up to 12 times faster.
 Myelin may be involved with the formation of habits*.
(Jensen, 2005; Sousa, 2008)*Non-declarative/Implicit memory
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16. Myelin-Producing Oligodendrocytes become Abundant in the Cerebrum
White Matter After Term (37 weeks gestation)
• Myelination is believed to be important for the development of
cognitive functions throughout childhood.
• The myelination of axons and neuronal connectivity begin
during the third trimester (week 27) of fetal development and
continues until early adulthood.
Premyelinating Oligodendrocytes do not Produce the Protein Myelin
(Nagy, Westerberg, & Klingberg, 2004; Mento & Bisiacchi, 2012; Volpe, 2009)

17. Premyelinating Oligodendrocytes Underlies White Matter Injury and
Alters the Time it Takes for Information to Reach Target Regions
A decrease in the total number of
neurons firing synchronously result in:
• the release of neurotransmitters at
fewer synapses at any particular time
• an upregulation of post-synaptic
receptors could compensate for this
phenomenon.
(Frye, et al., 2009; Back et al., 2007 in 2009; Khwaja and Volpe, 2008 in 2009)
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18. Sensory Information Travels through Myelinated Axons
(A2 nervesystemscolstons 2013, December 11 slide 9)

19. Information Travels through Myelinated Neurons at a Greater Velocity
(A2 nervesystemscolstons 2013, December 11 slide 8)
• Peripheral neurons have an insulating sheath around the axon called myelin which is formed by
Schwann cells.
• Myelin sheathing allows these neurons to conduct nerve impulses faster than in non-myelinated
neurons

20. Information is Transported through the Brain
Myelin sheathing has
bare sections of axons
called Nodes of Ranvier.
Action potentials (AP)
jump from node to node
(A2 nervesystemscolstons 2013, December 11, slide 7)

21. Myelin Increases the Velocity of the Information that
Flows through Axons
Continuous Conduction
• Action potentials are propagated along
each area of unmyelinated axons
continuously. This is a slow process.
Saltatory Conduction
• the propagation of action potentials
along myelinated axons from one node
of Ranvier to the next node, increasing
the conduction velocity of action
potentials.
(Jensen, 2005; Sousa, 2008; Ms Sime, April 16, 2016; Wikipedia: The Free Encyclopedia (15 December 2016).
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https://en.wikipedia.org/wiki/Saltatory_conduction#/media/File:Saltatory_Conduction.gif

22. End of
Fetal Brain Development and Cellular Functions
22
American Academy of Child & Adolescent Psychiatry, 2017