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-brainmap.html
Timelines of
Human Prenatal Development
Trimester
1st trimester
3rd trimester
2nd trimester
13
15
17
19
21
23
wk 16 - 25
EMBRYO
FETUS
wks 3 - 7
to birth
5
Specialization
wk 8 - 15
4
Aggregation
wk 0 - 7
3
Migration
Differentiation
2
Proliferation
Migration
1
Neural
Induction
Proliferation
"quickening"
1st trimester
wks 1 - 13
2nd trimester
wks 14 - 26
25
27
29
31
33
35
37
39
Continued
Differentiation
wk 26 - 39
viability
3rd trimester
wks 27 - 39
continue
postnatally
11
stages 5, 6, 7, 8
9
birth
7
8
Elimination
of
Connections
5
7
Cell Death
3
6
Connections
1
birth
Brain Growth Spurt (Dobbing) --> 2 yrs
OVUM
Ovum
Embryo
Fetus
Cowan
Brain Dvlp
Video Prenatal
week
Trimester
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
1. Neural Induction (~ days 16-23)
2. Cell proliferation
Begins once neural tube has closed off.
3. Migration
4. Aggregation
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
Fig.5
OVUM
1-2
FETUS (wks)
EMBRYO (wks)
3
4
5
6
7
8
•• =Most
=Most Common
Common Site
Site of
of Birth
Birth Defect
Defect
12
Central Nervous System
Heart
Arms
Eyes
Legs
Teeth
Palate
External genitalia
Ears
7
16
20-36
38
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
Normal development
Hands
Feet
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
Fig.5
OVUM
1-2
FETUS (wks)
EMBRYO (wks)
3
4
5
6
7
8
•• =Most
=Most Common
Common Site
Site of
of Birth
Birth Defect
Defect
12
Central Nervous System
Heart
Arms
Eyes
Legs
Teeth
Palate
External genitalia
Ears
14
16
20-36
38
3rd Week of Development
Neural Induction
15
first
missed
menstrual
period
16
primitive
knot
17
embryonic
mesoderm
18
neural
plate
19
neural fold
primitive
streak
20
brain
neural
groove
somite
notochord
prim.streak
trilaminar embryo
2-3 mm
thyroid developing
21
neural groove
somite
heart tubes
4th Week of Development
Proliferation & Migration
22
neural
folds
fusing
ant.
neuropores
heart
begins
to beat
23
post.
24
heart
bulge
2 prs
branch. arches
25
otic depression
3 prs
branch. arches
26
arm bud
27
28
4 pairs
branchial
arches
arm & leg buds
CR 4 - 5 mm
4th Week of Development
Proliferation & Migration
22
neural
folds
fusing
ant.
neuropores
heart
begins
to beat
23
post.
24
heart
bulge
2 prs
branch. arches
25
otic depression
3 prs
branch. arches
26
27
arm bud
28
4 pairs
branchial
arches
arm & leg buds
CR 4 - 5 mm
• hydrocephaly
• anencephaly
• hydroanencephaly
• spina bifida
Neural Tube Defects
Day 22
Spina Bifida
Radiation: Interferes with cell
migration and aggregation -stop too soon
Rat Brain: Normal Development
Proliferation -- Migration -- Aggregation
Days Later
16-17 DAY
13-14 DAY
Mature
20
nice, neat, cortical layers
Radiation on Days 13-14
Proliferation -- Migration -- Aggregation
Hours after
Irradiation
Days Later
13-14 DAY
Mature
subcortical ectopia
21
Radiation on Days 16-17
Proliferation -- Migration -- Aggregation
Hours after
Irradiation
Days Later
16-17 DAY
Mature
scrambled cortex
22
Alcohol: Interferes with migration.
Cell don’t stop
23
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 defects

Facial features: underdeveloped midface
Kathy Sulik
Alcohol-related birth defects

Underdeveloped 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 only
 Problems with attention
 Inhibition difficulties (start can’t stop)
• FAS 8:43
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
Disrupted school experiences
Easily victimized
Trouble with the law
Inappropriate sexual behavior
Alcohol and drug problems
Problems parenting
Problems living independently
www.faseout.ca 2008
94%
43%
72%
60%
45%
50%
FASD and Activities of Daily Living
Streissguth et al. Longitudinal Study (1996)
Sample of adults age 21+ were unable to:
–
–
–
–
–
–
–
–
–
–
–
Manage money
Make daily living decisions
Obtain social services
Get medical care
Handle interpersonal relationships 57%
Grocery shop
Cook meals
Structure leisure activities
Stay out of trouble
Maintain hygiene
Use public transportation
www.faseout.ca 2008
82%
78%
70%
68%
52%
49%
48%
48%
37%
24%
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