1. Running head: RISK AND PROTECTIVE FACTORS IN PRENATAL PROGRAMMING
Risk and Protective Factors in Prenatal Programming
Rebekah B. Cayzer and Jacob R. Stotler
The University of Wyoming
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Risk and Protective Factors in Prenatal Programming
Prenatal treatment is an essential part of a child’s life. During the perinatal periods of a
child’s life, the child is born into a world that has been (for nine months) built around the
“stores” and practices of the maternal nurturing (Eyles, Burne, & McGrath 2012, p. 48). When
the child is born, the child separates from what we aver as genetic and congenital, the child
begins a life built solely from the in-utero environment. The issues of supplying healthy levels of
needed nutrients, vitamins and hormones, and obeying to a healthy circadian cycle, and
preventing teratogens, perilous chemical exposures, drugs and other substances seems to be an
integral focus in promotion for a healthy child and person in later life.
One major connection that assimilates the fetus environment to the maternal environment
is that of the placenta. The placenta is said to be the largest fetal organ and may assist the
umbilical cord and fetus to receive at least 40% of the biventricular cardiac output of maternal
circulation (Hill, 2019; P. 2). The placenta contains what is known as a “blood barrier” in which
is biologically designed to filter wastes back through the maternal blood, to protect the fetus
from infiltrating substances, and to provide regulatory delivery of essential nutrients. Nutrients
are transported through the placenta by various forms of biological diffusion processes
(Goasdoue, Miller, Colditz & Bjorkman, 2017; P.1).
While the blood barrier functions in this way “most drugs ingested by a pregnant woman
during pregnancy can cross the placenta and reach the fetus” (Ostrea, Mantaring & Silvestre,
2004; P. 540). We are aware from research in the domain of the psychology of cognitive
development, that it is theorized that age related changes in cognitive development are believed
to stem from underlying changes in neurological development [and the maturation and health of
neuronal systems] (Galotti, 2017, p. 66). More so, vital brain developments happen prenatally,
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after about 16 weeks of gestation the blood barrier in the placenta becomes much more
permeable due to the reduction of thickness in the barrier; thus, the fetus becomes more
vulnerable to the substances circulating in the maternal visceral system (Ostrea, Mantaring &
Silvestre, 2004; P. 540).
Being that health starts within the womb and being so that not all health is restorable after
the perinatal period, we focus on the aspects and research of cognitive and human development
that involve creating and fostering the most substantial and robust preparations possible,
prenatally. The research is presented to provide an education about endowing the best possible
developmental advantage, regarding preparing a vulnerable fetus to flourish cognitively, and
outside of the womb.
During the fetal period stages of life, both protective factors and risk factors become
important sciences for the mother to attend to, the impact the mother has in the child’s life is
genetic, dispositional, neuroanatomical, preparational, and psychological. Some of these effects
instigated in antenatal periods are irreversible beyond the fetus stages (Anderson & Thomason,
2013; P. 2221; Eyles, Burne, & McGrath, 2012, P. 48).
Our research is based upon the research question: “What can be done in the first three
trimesters in pregnancy to solidify the best possible outcomes in cognition and psychology?” The
paper discusses the findings that neuro-generational factors such as vitamin D sufficiency and
proper nutrition can help enhance a child’s cognitive development even before birth. While too,
negative impacts on the development of the fetus can be accentuated by risk factors such as
reducing exposures to teratogens, medications, and lead [Pb-82] in the blood. We discuss the
findings that different factors can have an impact on a child’s cognitive development, both
positively and negatively, all before they leave the womb
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Risk Factors in Cognitive Development
Medications During Pregnancy
The different risk factors of cognitive development involved with pregnancies come in
different forms. One of the risk factors to the fetus is the medication a mother takes for her own
medical issues. There are some things women should be aware of when they discuss their
medications with their doctors. The domains of research into the effects of medication on
cognitive development for a baby is still a growing domain. One of these studies looks at the
effect of epileptic medications.
Barton, Nadebaum, Anderson, Vajda, Reutens, and Wood (2018) discuss their research on
how memory and learning is affected in children who were prenatally exposed to medication for
epilepsy. The research was conducted using women with epilepsy and their children; in total, the
study included 105 children between the ages of six and eight and their mothers. Children were
given comprehensive neuropsychological tests such as the Clinical Evaluation of Language
Fundamentals 4th
Edition (CELF-IV), Developmental Neuropsychological Assessment (NEPSY-
II), Rey Complex Figure (ROCF), Weschler Intelligence Scale for Children 4th
Edition (WISC-
IV) and the Wechsler Abbreviated Scale of Intelligence (WASI), which included four measures
assessing memory. The measures tested for intellectual functioning, language skills, working
memory, and verbal memory function. The mothers gave researchers family history information,
including their medical history during the pregnancy.
The results showed that the epilepsy medication did have influence on the children that were
exposed prenatally. The data that was gained suggested that children exposed to the epilepsy
medication had difficulty with learning, verbal memory, and non-verbal memory skills.
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When looking at these results there could be a few different meanings to be interpreted. One
could be how women with epilepsy could be or should be more informed of how the medications
that they use influence the memory development of their children, even from early stages of
gestation. This information may also imply the need to be more cautious during their pregnancies
and may emphasize the need for meeting with their doctors more often and talking about
specified issues of medication use regarding the effects onward to the child.
Another possible meaning of this research is that there is a need in medicine to discover new
or different methods of treatment for epilepsy in pregnant women to avoid effects on the fetus or
the child’s development. Research could be conducted to better monitor a child’s development
prenatally and after being born, to help mitigate issues related to maternal intake or medicinal
supplementation.
This study closely relates to Galotti’s (2017) research where Galotti discussed infant
memory. While implementing the research by Barton et. al (2018) to infant memory
development, we gain broader insight into the effects on child development in memory after
being exposed to medications prenatally. Thus, we can identify the health that is negatively
affected by the prenatal use of epileptic medications.
Lead [Pb-82]
Another risk factor for babies prenatally is prenatal exposure to lead [Pb-82]. One study
discusses about how lead was exposed to children in-utero and how lead exposure affected their
cognitive development after they were born.
Min et al. (2009) discussed a study that looked at the effects of early lead exposure and lead
in medicine affected a child’s IQ and academic achievement later in life. This study was able to
add more insight into how lead in medicine affected children who had been exposed to it as well
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as other substances prenatally. The participants were taken from a sample size of 278 children.
From this sample, participants were considered if the both the children and their mothers did not
face any other confounding psychiatric problem, low intellectual functioning, and if neither the
parent nor the child was currently positive for HIV. Children were accepted into the study if they
did not have Down syndrome, Fetal Alcohol Syndrome, or other medical illnesses.
At 4 years old, children had blood drawn to test the levels of lead and the children who had
lead in their blood were given the abbreviated Wechsler Preschool and Primary Scales of
Intelligence Revised (WPPSI-R) test. When they were reassessed at 9 and 11 years old, they
were tested again using the Entire Wechsler's Intelligence Scales for Children- Fourth Edition
(WISC-IV). The test gave the children’s full IQ and their Verbal and Performance IQ.
The results were significant enough to conclude that there are some correlational effects that
the lead exposure children had while in-utero, regarding their cognitive learning and the child’s
IQ. Another result showed that the lower reading scores were consistently associated with higher
lead exposure through preschool and elementary school ages. The study showed that lead levels
in children did have some effects on their academic performance and cognitive development.
These results relate back to information from Galotti’s research in the discussion about
cognitive skills in middle childhood. Specifically, Galotti (2017) discussed how these academic
skills develop in a child that is healthy and does not have any issues or pre-existing conditions.
Galotti’s work provides some background into how these skills develop in nonaffected children.
This helps when looking at the study done involving levels of lead in the blood as we can
compare how the children’s development should be as a control to that that have been exposed to
lead prenatally. These comparisons give us reason to adopt strategies to prevent lead exposure to
the parents and the child, and prenatally.
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Protective Factors in Cognitive Development
Vitamin D
While preventing known risk factors may be prominent to the optimal health of the child,
there are other factors a woman can consider and actions they can be taken to promote a healthy
cognitive development outcome for the child. One thing a mother could do is to assure that she
has ample nutrition and that she is intaking sufficient levels of requisite vitamins and minerals.
One vitamin that has been discovered to be a requirement for latter cognitive and neurological
development is vitamin D.
Eyles, Burne, and McGrath (2012) discuss a study conducted from archival research that is
based around investigation of vitamin D levels and subordinately, vitamin D deficiency
(hypovitaminosis D), and the effects from vitamin D deficiency that are associated empirically to
psychiatric disorders, and the relevant processes taking place chemically. The purpose of the
research presented, tells us that vitamin D deficiency is something majorly involved in
psychiatry and psychology, and that hypovitaminosis D, and maternal hypovitaminosis D cannot
be overlooked.
The article states that many disorders are relative and linked to levels of vitamin D in the
blood, both prenatally and postnatally. The article leaves claimant that after a certain period of
life, either antenatally or pre-birth, the deficiencies of these levels induce permanent effects to
development; the article states that the health does not or will not always replenish with the
adjustment of vitamin D levels thereafter (Eyles, Burne & McGrath, 2012) .
The line separating this deficiency from being replenishable or not, within the child’s life
can be called hereditary or genetic, as there is a transformation from nature to nurture; the article
states the prenatal fetus lives from the “store” of this vitamin from parental stores, intaking from
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the maternal circulations. The article makes point that these low maternal vitamin D levels are
known to be one risk factor of Autism Spectrum Disorder (ASD) (p. 57) and may be a
predeterminate of other psychiatric disorders such as Alzheimer's disease and depression (p. 48).
There is also a surfacing link between vitamin D levels and Multiple Sclerosis (p. 56) (Eyles,
Burne, & McGrath 2012, p. 48-56).
Eyles, Burne, and McGrath (2012) link these ossified damages of vitamin D deficiency to
additional or supplemental problems interfering with “neuronal differentiation [an acquisition
during development of specific biochemical, physiological and morphological properties by
nerve cells, where these cells develop in relation together] mentioning the connection between
presynaptic neurons to brain development (Biology online dictionary, 2019; Trafton, 2015);
axonal connectivity (between brain regions and can be focused on white matter (axonal-
connectivity), or within grey matter (neuronal-connectivity), dopamine ontogeny (the
development of dopamine systems since the earliest stages of development), and brain structure
and function.”
All of these natural transformations are relevant to brain development and have a direct
association with presynaptic neurons and the development of neuronal connections (Eyles,
Burne, & McGrath, 2012, p. 48; Trafton, 2015, p.1). The connections of nerve cells are a major
contributing component of how the brain will process information (Falvo & Holland, 2018, p.
34; University of Texas, 2019, p.3).
The study confers a report that there was a positive correlation found between adequate
vitamin D levels and performance on the Mini Mental State Examination (MMSE), and in
another study between vitamin D levels and scores on the Trail Making Task (TMT), and Digit
Symbol Substitution Test (DSST) (Eyles, Burne, & McGrath, 2012, p. 58). The article also
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introduces vitamin D mediating signaling in brain tissue, regulating axonal growth, regulating
calcium signaling in the brain, modulating the production of brain derived reactive oxygen
species, while also vitamin D may be a possible mechanism for enhancement of blood brain
barrier permeability. Vitamin D may proliferate cells in the brain. (Eyles, Burne & McGrath,
2012, p. 48)
Eyles, Brunes & McGrath (2012) also state that “vitamin D is a crucial differentiation factor
for developing brain cells,” and vitamin D may offer some neuroprotective effect against
excitotoxic agents; protection against Alzheimer’s and dopaminergic deficit / dopaminergic
neurotransmitter abnormalities, the vitamin can increase antioxidants in the brain (such as
glutathione). Vitamin D has putative anticonvulsant effects, and evidence irrefutably indicates
that “adequate Vitamin D levels are required for normal brain development and function” (Eyles,
Burne, & McGrath 2012, p. 55).
Connections from this research link to our studies in cognitive development, and through
many different lessons within the research by Galotti (2017). We learn that the generation of
synapses (connections between neurons), begins around birth, and reaches a “peak by about an
infant’s first birthday, and synaptic density reaches a peak within year number two” (p. 86).
During these first two years these axonal connections and neuronal differentiations do positively
connect with progressive changes in “perceptual development,” as this period is where “a lot of
perceptual development is enabled” (Galotti, 2017, p.86).
These connections are vital within the cerebral cortex, as neuronal differentiation and
neurons “form individual circuits that are specialized for each of the brain’s different
subsystems” (University of Texas, 2019, p. 1). We know these processes of neuron and axonal
development as a continuity dimension of development, as opposed to instantaneously / abrupt
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appearing changes known as discontinuity changes; changes in plasticity of these nuclei are
based upon the same neurons throughout life than were produced around 0-2 years old (Galotti,
2017, P. 68).
Adopted too, from Galotti (2017) we begin to understand why these neuronal connections
and axonal connectivity are important, just as well as neuronal generation, where individuals that
are found to have more dendrites, synapses, and neurons, these individuals are known to perform
better on some learning tasks. Galotti (2017) claims too, that certain brain structure maturity
involves the “cognitive achievements in the facets of vision, face recognition, visual tracking,
and high mental processes, such as planning and goal setting (fully developing during
adolescence years)” (Galotti, 2017, p. 106; p. 65).
The child faces crucial periods of development and exposure the entire journey through
gestation, and thus it seems that supplementing nutritional levels and sustaining adequate levels
of vitamin D may be vital for the health and proper development of the child. Sufficient levels of
vitamin D would foster the child for better cognitive outcomes by promoting optimal initial
neuronal development and neuronal connectivity, through the mechanisms of neurotrophic
factors and nerve growth factors as found by Ucuz, Dursun, Esin, Ozgeris, Kurt, Kuziltunc &
Zerrin (2015).
The connection between physiological development of neuronal connections and cognition /
perceptual development are presumed to be linked, though with limitations, Galloti (2017)
provides biological insight to this: “neurons in the cerebellum coordinate muscular activity and
coordination” (p. 65). Axonal connectivity / neuronal connectivity are known to be requisite
processes within the medulla, the pons, the central nervous system and brain [components] (p.
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65). These components are linked and communicate by nerves and neurons, these connections
make up what we know as the nervous system (Falvo & Holland, 2018, p. 6).
Neurotrophic factors promote survival and repair of the cells in the nervous system, and
neurotrophic factors are considered major probable mechanisms of the action of vitamin D in the
brain. Knowing this, we must again reflect that the sciences that state that neurons do not
regularly regenerate. The growth of original neurons in the human body, is estimated to be
entirely completed by the age of two years old (Galotti, 2017; Mayo Clinic, 2019; Ucuz et. al,
2015) which defines a very small window for optimal neuronal development.
Adequate levels of vitamin D were defined by Ucuz et. al (2015) as 20 ng / ml, and too by
Tello (2016) as being within the range of 40-60 ng /ml. It may be needed in the future for more
precise vitamin D levels to be identified to define the most optimal level of vitamin D in the
blood. We must conclude from these findings that a mother supporting and establishing
sufficient levels of vitamin D is one of the best preparatory care factors a mother can have
stabilized for her child while the child is still developing in the womb.
Limitations and Conclusion
From our research, we have found risk factors such as teratogens, medications, and lead
exposure can affect a child in a negative if not inimical way. However, there are protective
factors as well that a mother can propagate to help stimulate the cognitive development of the
child, such as supplementing vitamin D to medically appropriate levels.
Through the research, we found connections to Galotti’s text in different ways, such as
memory being affected by epileptic medicine and children’s academic performances being
affected by lead exposure. We also defined important connections between intaking vitamin D,
and the promotion of healthy synapse generation and brain development.
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One major point explained in our research is that a woman’s decisions during pregnancy can
affect her child’s cognitive development, either positively or negatively, and accordingly to the
contact the mother has or indirectly induces onward to the fetus. The different studies mentioned
show different connections of psychology and increase our understanding of prenatal and
perinatal care and the vulnerability of the fetus to the biological and congenital leadership of the
mother. The research prescribes the maternal mother to be vigilant for both her herself and the
child, for both are circulating her exposures.
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References
Anderson, A. & Thomason, M. (2013). Functional plasticity before the cradle: a review of neuronal
functional imaging in the human fetus. Neuroscience & Biobehavioral Reviews. (37). 9. Part B.
P. 2220-2232. Retrieved April 8, 2019 from https://doi.org/10.1016/j.neubiorev.2013.03.013.
Barton, S., Nadebaum, C., Anderson, V. A., Vajda, F., Reutens, D. C., & Wood, A. G. (2018).
Memory dysfunction in school-aged children exposed prenatally to antiepileptic drugs.
Neuropsychology, 32(7), 784-796. doi:10.1037/neu0000465.
Biology Online Dictionary. (2019). Neuronal Differentiation. [Online entry]. Retrieved March 28,
2019 from https://www.biology-online.org/dictionary/Neuronal_differentiation.
Eyles, D., Burne, T.H.J. & McGrath, J.J. (2012). Vitamin D, effects on brain development, adult
brain function and the links between low levels of vitamin D and neuropsychiatric disease.
Frontiers in Neuroendocrinology. 34. P. 47-64. Retrieved March 31, 2019 from
https://doi.org/10.1016/j.yfrne.2012.07.001. Elsevier Inc.
Falvo D. & Holland, B. (2018). Medical and Psychosocial Aspects of Chronic Illness and Disability.
6. Jones & Bartlett Learning LLC.
Goasdoue, K., Miller, S., Colditz, P. & Bjorkman, T. (2017). Review: the blood-brain barrier;
protecting the developing fetal brain. Placenta, (54); P. 111-116. Elsevier publishing. Retrieved
April 30, 2019 from https://doi.org/10.1016/j.placenta.2016.12.005.
Galloti, K. (2017). Cognitive Development Infancy Through Adolescence. 2. P. 1-300. Sage
Publication, Inc. ISBN: 978-1-4833-7917-3.
Hill, M. (2019). Embryology. Placenta Development. Retrieved April 30, 2019 from
https://embryology.med.unsw.edu.au/embryology/index.php/Placenta_Development.
14. RISK AND PROTECTIVE FACTORS IN PRENATAL PROGRAMMING 14
14
Mayo Clinic. (2019). Neuro-regeneration. Center For Regenerative Medicine [online scholarly
article]. Retrieved May 1, 2019 from https://www.mayo.edu/research/centers-programs/center-
regenerative-medicine/focus-areas/neuroregeneration.
Min, M., Singer, L., Kirchner, H., Minnes, S., Short, E., Hussain, Z., & Nelson, S. (2009).
Cognitive development and low-level lead exposure in poly-drug exposed children.
Neurotoxicology and Teratology, 31(4), P. 225-231. doi:10.1016/j.ntt.2009.03.002.
Ostrea, E., Mantaring, J. & Silvestre, M. (2004). Drugs that affect the fetus and newborn infant via
the placenta or breast milk. Pediatrics Clinics of North America, (510), P. 539-579. Elsevier
Publishing. Retrieved April 30, 2019 from
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.379.9919&rep=rep1&type=pdf.
Tello, M. (2016). Vitamin D: what’s the “right” level? Harvard health Publishing. Harvard medical
School. [Online article]. Retrieved March 11, 2019 from
https://www.health.harvard.edu/blog/vitamin-d-whats-right-level-2016121910893 .
The University of Queensland Australia. (2019). Central nervous system: brain and spinal cord.
Queensland Brain Institute. [Online article]. Retrieved April 7, 2019 from
https://qbi.uq.edu.au/brain/brain-anatomy/central-nervous-system-brain-and-spinal-cord.
Trafton, A. (2015). Neuroscientists reveal how the brain can enhance connections, newly identified
mechanisms allows the brain to strengthen links between neurons. Massachusetts Institute of
Technology News. Retrieved April 7, 2019 from http://news.mit.edu/2015/brain-strengthen-
connections-between-neurons-1118.
Ucuz, I., Dursun, O., Esin, S., Ozgeris, F., Kurt, N., Kiziltunc, A. & Zerrin, O. (2015). The
relationship between Vitamin D, autistic spectrum disorders, and cognitive development: do glial
cell line derived neurotrophic factor and nerve growth factor play a role in this relationship?
15. RISK AND PROTECTIVE FACTORS IN PRENATAL PROGRAMMING 15
15
International Journal of Developmental Disabilities. (4). 61. P. 222-230. Retrieved March 7,
2019 from
http://libproxy.uwyo.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=cc
m&AN=118198694&site=ehost-live.
University of Texas. (2019). Neurons and circuits. Department of Computer Science of the
University of Texas. [E-book excerpt]. P. 1-21. Retrieved April 7, 2019 from
http://www.cs.utexas.edu/~dana/Ch3.pdf.
Yarlagadda, A. & Clayton, A. (2007). Blood brain barrier, The role of Pyridoxine. Psychiatry
(Edgemont). Retrieved April 6, 2019 from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880949/.