Fostering Healthy Prenatal Development
Outline
• Preconception• Stages of development from conception to birth• What can interfere with healthy development
– Teratogens• Alcohol
– Low Birth weight
• Prevention• Cool Tool: http://www.zerotothree.org/baby-brain-
map.html
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FETUSto birth
Proliferation wk 0 - 7
Migrationwk 8 - 15
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Differentiation wk 16 - 25
ContinuedDifferentiation wk 26 - 39
Brain Growth Spurt (Dobbing) --> 2 yrs
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Tri-mester
1st trimester 2nd trimester 3rd trimester
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Timelines of Human Prenatal Development
Tri-mester
Stages of prenatal development
• 1st trimester : Organ development; Nervous system– Cells multiply– Cells specialize and migrate to where they should be to be
part of certain organs
• 2nd trimester– Nerve cells proliferate and form connections– External organs continue to be laid down
• 3rd trimester– Brain growth spurt– Can hear sounds– Getting ready to come out: lungs very immature
Cowan's Eight Stages in Brain Development
Cowan's Eight Stages in Brain Development
1. Neural Induction (~ days 16-23)
2. Cell proliferationBegins once neural tube has closed off.
3. Migration
4. Aggregation
Cowan's Eight Stages in Brain Development (cont.)
Cowan's Eight Stages in Brain Development (cont.)
• 5. Specialization of immature neurons (16-25 wks)– a. elaboration of processes – b. adoption of mode of transmission
• 6. Formation of Connections • 7. Selective Cell Death • 8. Selective Elimination of Connections
7
OVUM EMBRYO (wks) FETUS (wks)
HeartArms
EyesLegs
TeethPalate
Ears
Fig.5Fig.5
External genitalia
Central Nervous System
• =Most Common Site of Birth Defect1-2 3 4 5 6 7 8 12 16 20-36 38
• =Most Common Site of Birth Defect
What can interfere with healthy development
• Teratogens: literally means “creates monsters”– Now used to mean anything that mother exposed to
that interferes with prenatal development in ways that cause:
• Birth defects (visible at birth)• Behavioral Difficulties (behavioral teratogens)
• Low birth weight– Prematurity– Low weight for gestational age
1. Teratogens
• How effect fetus/embryo– directly as in radiation
• Cross from mother’s body through placenta– Alcohol, infections
• Affect gene’s environment
• Examples– Thalidomide (drug)– Infections -- Rubella (measles) – Radiation– Alcohol
Thalidomide Warning
Label
10
Thalidomide Deformities
Hands
Feet
Normal development
Effects of time of exposure (3.5 - 7 wks gestational age) on limb deformities
Thalidomide Deformities
Effects of teratogens
• Critical periods of exposure– Embryo or fetus vulnerable to specific problems
during specific times when undergoing a particular developmental process. (e.g., female fetus may have genital malformations if exposed to androgens <male sex hormone> during 10th week of gestation).
– 1st trimester (especially 1st two months): organs, limbs, shape)
– 2nd & 3rd trimester: brain size (less visible effects); size of fetus
• Vulnerability of fetus (some tougher than others)• General health of mother
14
OVUM EMBRYO (wks) FETUS (wks)
HeartArms
EyesLegs
TeethPalate
Ears
Fig.5Fig.5
External genitalia
Central Nervous System
• =Most Common Site of Birth Defect1-2 3 4 5 6 7 8 12 16 20-36 38
• =Most Common Site of Birth Defect
15 16 17 18 19 20 21
embryonicmesoderm
trilaminar embryo
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primitiveknot
prim.streak
neuralplate
neural fold
notochord2-3 mm
neural groove
neuralgroove
brain
somitesomite
thyroid developing heart tubes
3rd Week of Development3rd Week of DevelopmentNeural Induction
4th Week of Development4th Week of Development
22 23 24 25 26 27 28
4 pairsbranchialarches
arm & leg buds
heartbeginsto beat
neural folds fusing ne
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CR 4 - 5 mm3 prsbranch. arches
otic depression
Proliferation & Migration
4th Week of Development4th Week of Development
22 23 24 25 26 27 28
4 pairsbranchialarches
arm & leg buds
heartbeginsto beat
neural folds fusing ne
uro
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post.
ant. heart bulge
2 prsbranch. arches
arm bud
CR 4 - 5 mm3 prsbranch. arches
otic depression
Proliferation & Migration
• hydrocephaly
• anencephaly
• hydroanencephaly
• spina bifida
Neural Tube DefectsDay 22 Spina Bifida
Radiation: Interferes with cell migration and aggregation --
stop too soon
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Rat Brain: Normal DevelopmentRat Brain: Normal Development
Proliferation -- Migration -- Aggregation
13-14 DAY
16-17 DAY
Days Later
Mature
nice, neat, cortical layers
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13-14 DAY
Hours afterIrradiation
Days Later
Mature
Radiation on Days 13-14Radiation on Days 13-14
Proliferation -- Migration -- Aggregation
subcortical ectopia
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16-17 DAY
Hours afterIrradiation
Days Later
Mature
Radiation on Days 16-17Radiation on Days 16-17
Proliferation -- Migration -- Aggregation
scrambled cortex
Alcohol: Interferes with migration.Cell don’t stop
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Alcohol as a Teratogen
• Negative effects throughout gestation– Neurological Damage– Retarded Physical Growth– Face and organ malformations
• Unknown what’s a safe dose• Leading known environmental cause of mental
retardation• 5-10% of women of child-bearing age have
alcohol problem
Alcohol-related birth defectsAlcohol-related birth defects
Facial features: underdeveloped midfaceFacial features: underdeveloped midface
Kathy Sulik
Alcohol-related birth defectsAlcohol-related birth defects
Underdeveloped brainUnderdeveloped brain
Fetal Alcohol Syndrome (12,000 a year in U.S.)
• Mild retardation -- IQ 65-80
• Difficulty with reasoning and planning
• Distractable
• Don’t learn from mistakes
• Indiscriminate affection
• Verbal > Reasoning
(Anne Streissguth, U of Washington c.1970)
Fetal Alcohol Spectrum Disorder (36,000 a year in U.S.)
More common but less severe form of the syndrome
Effects evident in behavior onlyProblems with attention Inhibition difficulties (start can’t stop)
Learning about the effects of alcohol
• Correlational studies in humans – Correlations show whether two things
tend to be found together– Don’t prove cause
• Experimental studies with animals
Correlational studies in humans: Limitations
• Difficult to accurately estimate level of alcohol exposure.– Amount mother ingests
- Amount fetus/embryo exposed to
• Can’t rule out alternative causes of problems child might be showing: Correlated risks
• Difficult to study effects of exposure during specific periods
Experimental studies with animals
• Advantages: – Control when and how much exposed.– Compare to control group similar except for
exposure to alcohol– Infer that alcohol causes differences in offspring.– Look in a fine grained way at how alcohol
exposure disrupts brain development.
• Disadvantages:– Unclear how findings apply to humans especially
for things that only humans do.
Findings from animal studies
• Ist trimester: – Facial malformations, worse for growth and
behavior than later exposure.– Effects on behavior even in the absence of
obvious physical defects.
• Effects to nervous system due to exposure in only 2nd and 3rd trimester.
2nd semester
– When nerve cells are generated and go to appropriate regions of the brain
– Effects• Nerve cell generation delayed
– Fewer produced.– Nerve cells don’t go where they are supposed to
go.– Unusual cell formations in
• hippocampus – learning,memory & emotion• cerebellum – motor ability
3rd trimester
• Interferes with brain growth spurt– Brain weight & head circumference reduced– Fewer cells in cerebellum & hippocampus
• These anatomical changes are related to animal equivalent of hyperactivity and learning deficits.
Humans: What can we tell about effect of alcohol on behavior
– Early, heavy drinking leads to most severe problems:
• mental retardation• sensory deficits (vision, hearing)• motor problems
– Facial abnormalities: 1st 8 weeks (comparison of women who stopped or continued: M = 24 drinks per week)
Human Behavior cont.
– Even in the absence of physical effects: • learning and attention problems.
– Moderate early drinkin leads to more subtle learning difficulties and attention problems.
– Hyperactivity, language difficulties, motor deficits greater when Mom drank through pregnancy than stopped after 1st trimester
– Weight, length, head circumference affected by drinking later in pregnancy
– Being alcohol free during 3rd trimester allows growth catch up.
FASD Adults
• The following secondary effects were ascertained from life history interviews of 415 FASD affected individuals using 450 questions
• Dr Anne Streissguth, et al, University of Washington
www.faseout.ca 2008
Secondary Disabilities• Mental health problems 94%• Disrupted school experiences 43%• Easily victimized 72%• Trouble with the law 60%• Inappropriate sexual behavior 45%• Alcohol and drug problems 50%• Problems parenting• Problems living independently
www.faseout.ca 2008
FASD and Activities of Daily LivingStreissguth et al. Longitudinal Study (1996)
Sample of adults age 21+ were unable to: – Manage money 82%– Make daily living decisions 78%– Obtain social services 70%– Get medical care 68%– Handle interpersonal relationships 57%– Grocery shop 52%– Cook meals 49%– Structure leisure activities 48%– Stay out of trouble 48%– Maintain hygiene 37%– Use public transportation 24%
www.faseout.ca 2008
Implications for intervention
• FAS and FAE are common preventable problems.
• How can we develop interventions that work?
• Type of intervention– Primary, secondary, tertiary– How should be target?– Getting knowledge to people– Motivation to change– Learning from people who have changed
2. Preventing low birth weight babies
• Who has low birthweight babies:– Poverty nexus of risk– Multiple births through infertility treatment
Why? At risk for
• medical problems• developmental problems such as
cerebral palsy• higher risk of mortality
Role of life style factors in preventing low birth weight
Nutritional and weight gain
• Risk factors:– Low income/limited food budgets– Stress and distress– Lack of knowledge about proper nutrition– Smoking, alcohol
Life style choices: Cigarette smoking, alcohol, caffeine, and illegal drugs
• Risk factors:– Stress and distress– Lack of knowledge about their effects– Lack of support for stopping addictive behavior
• Quitting smoking at any point has positive effect on birth weight.Smoking after birth increases child’s risk of respiratory problems (most women who quit during pregnancy start again after the child’s birth).
Stress
• neuroendocrine functioning• depresses immune system• Affects health behaviors
– decreases likelihood of prenatal care– increases likelihood of smoking, drinking
• Anxiety may increase metabolism• Depression affects appetite, sleep
Employment
• Benefit: health insurance, income• Possible problems:
– exposure to toxins– work related stress and fatigue– work overload may interfere with eating
regularly
Domestic violence
• Physical abuse can lead to – early onset of labor– neglect of prenatal care, chronic medical
conditions
Sexually transmitted diseases
• various infections linked with low birth weight and preterm babies.
Directions for prevention and intervention
• Learn from women who despite living in economically depressed or stressful situations, – don’t engage in high-risk behaviors that may have a
detrimental effect on their child during pregnancy– who have been able to change.
• Apply the lessons learned to intervention programs.
•
Change
• Pregnancy is an opportunity for change. – Women want healthy babies – More likely to
• seek information about healthy behavior• make changes in their own lives during or before
pregnancy.
• Benefits: – OWN HEALTH SHORT TERM AND LONGTERM– INCREASES LIKELIHOOD OF HEALTHY BABY– POSTNATAL HEALTH OF BABY– IMPROVES HEALTH OF ENTIRE FAMILY (CHANGES IN DIET)
Barriers to change
– Life circumstances that require focus on day-to-day survival.
– Unavailability of health care.– Development of addictive behaviors long before
pregnancy makes it hard to stop during pregnancy
• Case of smoking– ads targeting young women– societal concern about weight