Environmental Influences on Human Development Flashcards by Joel Glotfelty

Toxic or infectious insults occurring in the first few weeks of development are likely to be

Fatal

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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

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What are three highly potent xenobiotic teratogens?

) Alcohol
) Cocaine
) Smoking

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Begins to form in week three an is particularly vulnerable up to week 8 or 10

Heart

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Rubella infection between weeks 3-8 of embryonic development results in

Cardiac defects

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Can lead to cardiac defects, eye abnormalities, and deafness

Rubella infection during pregnancy

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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”

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Teratogenesis is defined as

Birth defects

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Two of the most pervasive in utero toxicants are

Tobacco smoking and alcohol

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Are among the most important child health problems in the US

Developmental disabilities

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What precentge of children have some developmental disability

17%

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What percentage of children have ADHD?

3-7%

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About 7-12/1,000 children have some form of

Autism spectrum disorder

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Occur in a complex context shaped by genetic determination or predilection (susceptibility), social circumstances, and personal lifestyles

Environmental exposures

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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

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The process resulting in defects apparent at birth due to some interference with normal development

Teratogenesis

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Agents that have been identified to cause birth defects such as Rubella, alcohol, mercury, lead, etc are called

Teratogens

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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

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During fetal development, folic acid deficiency has been associated with a spectrum of neural tube defects such as

Spina bifida

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The extreme case of folic acid deficiency during pregnancy is

Anencephaly

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When is the vulnerable period for folic acid deficiency in pregnancy?

-when the neural tube is forming and then closing

First trimester

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At birth, small skull circumference and flattened skull are evidence of this severe, usually fatal defect

Anencephaly

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Should be taken as a supplement before and during pregnancy

Folic acid

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What percentage of developmental defects in man are thought to be caused by drugs and environmental chemicals?

4-5%

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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 1. ) Ears and eyes 2. ) Upper limbs 3. ) Lower limbs

1. ) 20th-25th day 2. ) 26th-30th day 3. ) 31st-36th day

Congenital Rubella Syndrome (CRS) presents as a classic triad of

1. ) Sensorineural deafness (60%) 2. ) Congenital heart disease (50%) 3. ) 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?

1. ) At birth 2. ) Shortly after birth 3. ) Delayed until puberty 4. ) 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

1. ) Elemental mercury (quicksilver) 2. ) Inorganic mercury (mainly pigments) 3. ) Organic mercury

What are the two organic forms of mercury

1. ) 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