Environmental Influences on Human Development Flashcards
Toxic or infectious insults occurring in the first few weeks of development are likely to be
Fatal
States that if an action or policy has a suspected risk of causing harm to the public or environment, even in the absence of scientific consensus, the burden of proof that it is NOT HARMFUL falls on those taking action, such as the introduction of a chemical or a pharmaceutical
Precautionary Principle
What are three highly potent xenobiotic teratogens?
- ) Alcohol
- ) Cocaine
- ) Smoking
Begins to form in week three an is particularly vulnerable up to week 8 or 10
Heart
Rubella infection between weeks 3-8 of embryonic development results in
Cardiac defects
Can lead to cardiac defects, eye abnormalities, and deafness
Rubella infection during pregnancy
Points in development at which an insult (pharmaceutical, toxic, or infectious) may have a specific, profound impact on certain targets that are vulnerable at that time
“Critical periods” or “Sensitive Windows”
Teratogenesis is defined as
Birth defects
Two of the most pervasive in utero toxicants are
Tobacco smoking and alcohol
Are among the most important child health problems in the US
Developmental disabilities
What precentge of children have some developmental disability
17%
What percentage of children have ADHD?
3-7%
About 7-12/1,000 children have some form of
Autism spectrum disorder
Occur in a complex context shaped by genetic determination or predilection (susceptibility), social circumstances, and personal lifestyles
Environmental exposures
The fair treatment and meaningful involvement of all people regardless or race, color, national origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies
Environmental Justice
The process resulting in defects apparent at birth due to some interference with normal development
Teratogenesis
Agents that have been identified to cause birth defects such as Rubella, alcohol, mercury, lead, etc are called
Teratogens
A vitamin that is not manufactured in the body and must be consumed in the diet. It is associated with anemia in adults
Folic acid
During fetal development, folic acid deficiency has been associated with a spectrum of neural tube defects such as
Spina bifida
The extreme case of folic acid deficiency during pregnancy is
Anencephaly
When is the vulnerable period for folic acid deficiency in pregnancy?
-when the neural tube is forming and then closing
First trimester
At birth, small skull circumference and flattened skull are evidence of this severe, usually fatal defect
Anencephaly
Should be taken as a supplement before and during pregnancy
Folic acid
What percentage of developmental defects in man are thought to be caused by drugs and environmental chemicals?
4-5%
Relative teratogenicity is influenced by
Maternal factors
Developmental defects increase with frequency and degree as a function of
Fetal dose of teratogen
Teratogenic susceptibility is greatest during
Organogenesis
What is one example of a human condition that was not predicted by animal studies?
Congenital Rubella Syndrome (CRS)
Animal studies predicted some but not all
Thalidomide toxicity
A drug used to prevent miscarriage
Diethylstilbestrol (DES)
In the case of diethylstilbestrol (DES), animal studies did not show
Vaginal legions in F1 offspring
What does the acronym TORCH stand for?
T = Toxoplasma O = Other (Zika, chicken pox, syphillis, etc) R = Rubella C = Cytomegalic virus H = Herpes
Most cause mild maternal morbidity, but have serious fetal consequences
TORCH infections
The treatment of maternal TORCH infection typically has no impact on
Fetal outcome
What are two examples of fetal outcomes from TORCH infections?
Microcephaly and mental retardation
What is the critical window for Rubella and Zika?
3-16 weeks
Caused by the togovirus and generally show mild flu-like symptoms + rash in children
Rubella (German measles)
The incubation period for Rubella is
2-3 weeks
When Rubella occurs during pregnancy, the highest risk percentage for developing Congenital Rubella Syndrome (CRS) is during the
1st trimester (50-90% results in CRS)
What percentage of Rubella infection during the 2nd trimester results in CRS?
25%
What are the critical or sensitive developmental periods for the
- ) Ears and eyes
- ) Upper limbs
- ) Lower limbs
- ) 20th-25th day
- ) 26th-30th day
- ) 31st-36th day
Congenital Rubella Syndrome (CRS) presents as a classic triad of
- ) Sensorineural deafness (60%)
- ) Congenital heart disease (50%)
- ) Ocular abnormalities (45%)
The reason the MMR vaccine was developed
Congenital Rubella Syndrome (CRS)
The MMR vaccine is contraindicated during
Pregnancy
Flavivirus spread primarily by the bite of infected Aedes aegypti or Aedes albopictus
Zika Virus
Many adults with this virus are asymptomatic or have mild flu-like symptoms
Zika Virus
However, Zika can cause
Severe birth defects, stillbirths, and miscarriages
The flavivirus was first recognized in Brazil in early
2015
The zika virus has been directly correlated to
Microcephaly
Characterized by fetal death, still birth, neonatal death, and developmental impairment
Congenital Zika Syndrome
Results in severe thinning of cortex
Zika
Unlike other flaviviruses, Zika can also be detected in high quantity in
Semen
Can be transmitted sexually from male to pregnant female
Zika
Vitamin needed for DNA synthesis
Folate (Vitamin B-9)
Lack of animal protein and green vegetables in the diet, maternal smoking, alcohol, and kidney dialysis can all cause
Folate deficiency
What is the most common cause of preventable mental retardation?
Fetal Alcohol Syndrome
What is the incidence of fetal alcohol syndrome?
5-12K births / year
Characterized by facial abnormalities, marked hyperactivity, delayed gross and fine motor skills, delayed learning and language skills,and hearing loss
Fetal Alcohol syndrome
How many drinks per day during pregnancy essentially guarantees fetal alcohol syndrome?
4-5 drinks per day
Clinically significant deficits are not common in children whose mothers drank less than approximately
5 drinks per occasion, once a week
A sedative used for morning sickness that showed no toxicity in animal studies but causes major problems in human births
Thalidomide
In adults, thalidomide toxicity leads to
Neuropathy, GI stasis, and dizziness/disorientation
As a teratogen, leads to phocomelia, amelia, syndactyly, and ear and eye defects
- > 10,000 affected children worldwide (less than 100 in US)
Thalidomide
In 2010, it was suggested that the mechanism of action of thalidomide teratogenicity was the arrested development of
Critical blood vessels
Thalidomide has recently been shown to have beneficial uses and has been used for
Multiple myeloma, Leprosy, and difficult dermatology cases
Thalidomide has been used to manage leprocy in
Brazil
One of the most dramatic examples of drug interference during development comes (FOAD) from the experience with which drug that was widely used in pregnant women with “threatened abortion” from the 1940s through the 1960s
Diethylstilbesterol (DES)
Diethylstilbesterol (DES) was used to prevent
Miscarriages
Researchers then discovered that DES caused
Vaginal tumors in female offspring
DES sons are at risk for
Non-cancerous epidermal cysts
Female offspring of DES-treated mothers developed clear-cell adenocarcinoma of the vagina shortly after the onset of the
Menarche
What is the critical period of maternal exposure to DES?
1st trimester
DES causes problems because there are Estradiol sensitive adenomatous tissues in the
Vagina
Researchers learned that the placenta is NOT a
Complete barrier
Studies showed that fetal susceptibility is maternally determined and is dependent on
Gestational stage
In utero, toxicity can be manifested at what four stages?
- ) At birth
- ) Shortly after birth
- ) Delayed until puberty
- ) Decades after birth
How many generations can show toxicity in utero?
F2+n generations
Probably the only known example of F2 effects in humans are
DES effects
Many teratogens cause restriction of
Intrauterine growth
Showed how prenatal and infant events or exposures can program an individual for adult disease
Fetal Origins of Adult Disease (FOAD)
FOAD showed that birth size (small babies that become obese children) predicts
Hypertension, cardiovascular disease, glucose intolerance, and dyslipidemias
Chronic stress and corticoid stimulus leads to
Intrauterine Growth Restrictions (IUGR)
The Dutch famine of 1944-45 showed that first trimester exposure had no effect, but third trimester exposure led to
Glucose intolerance
Intrauterine growth restriction (IUGR) occurs during which weeks of the fetal period?
16-38
Substances that interfere with normal hormone functions cause
Endocrine Disruption
Can be do to up or down regulation of hormone production, release, or receptor expression
Endocrine disruption
Hormone agonists or antagonists can lead to
Endocrine disruption
All forms of this element are toxic to all animals
Mercury
Used as an antiseptic, a biocide in paints and on crops, and as a diuretic
Mercury
What are the three main forms of mercury
- ) Elemental mercury (quicksilver)
- ) Inorganic mercury (mainly pigments)
- ) Organic mercury
What are the two organic forms of mercury
- ) Ethyl mercury (Thimerosal)
2. ) Methyl mercury (mainly from fish)
People who eat fish that are high on the food chain several times a week are susceptible to
Methylmercury poisoning
Elemental and inorganic mercury are mainly a problem
for
Industrial exposures
The more highly toxic form of mercury
-Targets the CNS
Methylmercury
A ubiquitous contaminant that is mainly of concern for fetal development if mothers consume large amounts of fish that are high on the food chain
Mercury
An amount of a substance that can be consumed on a daily basis without causing adverse effects
Reference dose
Merely exceeding a reference dose does not predict
-would have to exceed by a lot
Harm
There were two conflicting studies done on mercury in fish, one by Harvard and one by Rochester university. The EPA decided to base it’s reference dose on the
Harvard study (0.1 ug/kg body weight)
The FDA decided to base it’s allowable daily intake on the Negative findings from the Rochester study and set it at
0.3 ug/kg body weight
The Rochester study in the Republic of Seychelles measured maternal hair samples for Hg during pregnancy. The study showed no significant impact from prenatal exposure of Hg on
Neurodevelopment
Since the reference dose of Hg is 0.1 ug/kg body weight/day, this means that during pregnancy, if mercury intake is below 0.1 ug/kg body weight/day, there should be
NO adverse effects